Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To ad...Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To address these challenges,IL-2-So-Lipo,a novel liposomal formulation combining IL-2 with sorafenib derivative,was developed as an anti-angiogenic drug that inhibits the growth of new blood vessels which play crucial roles in tumor growth.Sorafenib derivatives could target at melanoma-specific receptors,further enhancing liposomal specificity at the tumor site.Our results demonstrated that the prepared IL-2-So-Lipo significantly enhanced anti-tumor activity compared to IL-2 or sorafenib monotherapies,as well as their combination.In a B16F10 melanoma model,IL-2-So-Lipo was found to significantly inhibit tumor progression(tumor volume of 108.01±62.99 mm^(3))compared to the control group(tumor volume of 1,397.13±75.55 mm^(3)),improving the therapeutic efficacy.This enhanced efficacy is attributed to the targeted delivery of IL-2 which promoted the infiltration and activation of cytotoxic T lymphocytes.Additionally,liposomal encapsulation of sorafenib derivatives enhanced its delivery efficiency,promoting tumor cell apoptosis and suppressing angiogenesis.Mechanistically,IL-2-So-Lipo could kill tumors by inducing a shift towards an anti-tumor immune response via facilitating the polarization of macrophages towards the M1 phenotype.Furthermore,IL-2-So-Lipo downregulated several key proteins in the MAPK signaling pathway,exerting a significant role in mediating tumor resistance to sorafenib.These findings underscore the potential of IL-2-So-Lipo as a promising strategy to improve the therapeutic efficacy of immunotherapy and targeted therapy in cancers.Moreover,the combination of IL-2 and sorafenib in a liposomal delivery system overcame the limitations of conventional IL-2 therapy,offering a synergistic approach to improve therapeutic outcomes for solid tumors.展开更多
Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal a...Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal anti-inflammatory drugs(NSAIDs),and corticosteroids,frequently result in unintended adverse effects.Dexamethasone(DEX)is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties.Liposomal delivery of DEX,particu-larly when liposomes are surface-modified with targeting ligands like peptides or sialic acid,can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity.This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA.Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models,reduces joint inflammation and damage,and alleviates cartilage destruction compared to free DEX.The liposomal formulation also shows better hemocompatibility,fewer adverse effects on body weight and immune organ index,and a longer circulation time with higher bioavailability.The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α(TNF-α)and B-cell-activating factor(BAFF),which are key players in the pathogenesis of RA.Additionally,liposomal DEX can induce the expres-sion of anti-inflammatory cytokines like interleukin-10(IL-10),which has significant anti-inflammatory and immunoregulatory properties.The findings suggest that lipo-somal DEX represents a promising candidate for effective and safe RA therapy,with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.展开更多
Liposomes serve as critical carriers for drugs and vaccines,with their biological effects influenced by their size.The microfluidic method,renowned for its precise control,reproducibility,and scalability,has been wide...Liposomes serve as critical carriers for drugs and vaccines,with their biological effects influenced by their size.The microfluidic method,renowned for its precise control,reproducibility,and scalability,has been widely employed for liposome preparation.Although some studies have explored factors affecting liposomal size in microfluidic processes,most focus on small-sized liposomes,predominantly through experimental data analysis.However,the production of larger liposomes,which are equally significant,remains underexplored.In this work,we thoroughly investigate multiple variables influencing liposome size during microfluidic preparation and develop a machine learning(ML)model capable of accurately predicting liposomal size.Experimental validation was conducted using a staggered herringbone micromixer(SHM)chip.Our findings reveal that most investigated variables significantly influence liposomal size,often interrelating in complex ways.We evaluated the predictive performance of several widely-used ML algorithms,including ensemble methods,through cross-validation(CV)for both lipo-some size and polydispersity index(PDI).A standalone dataset was experimentally validated to assess the accuracy of the ML predictions,with results indicating that ensemble algorithms provided the most reliable predictions.Specifically,gradient boosting was selected for size prediction,while random forest was employed for PDI prediction.We successfully produced uniform large(600 nm)and small(100 nm)liposomes using the optimised experimental conditions derived from the ML models.In conclusion,this study presents a robust methodology that enables precise control over liposome size distribution,of-fering valuable insights for medicinal research applications.展开更多
Abnormal wound scarring often leads to functional impairments and cosmetic deformities,primarily driven by the prolonged activation of the TGF-β/Smad signaling pathway.Addressing this challenge,we developed a biomime...Abnormal wound scarring often leads to functional impairments and cosmetic deformities,primarily driven by the prolonged activation of the TGF-β/Smad signaling pathway.Addressing this challenge,we developed a biomimetic scaffold aimed at facilitating rapid and scarless wound healing.This highly in-tegrated 3D-printed dermal scaffold comprised modified recombinant human type III collagen(rhCOLIII-MA),gelatin methacrylate(GelMA),and liposomes encapsulating SB431542 to target TGF-β1(Lip@SB).The rhCOLIII-MA/GelMA(CG)scaffold retained inherent biomaterial characteristics,exhibited tailored physicochemical properties,and demonstrated favorable biocompatibility.Moreover,the Lip@SB-loaded CG scaffold(CGL)effectively promoted in vitro wound healing,while enabling controlled release of SB431542 to inhibit pathological collagen deposition.In a full-thickness skin defect rat model,the CGL dermal scaffold combined with split-thickness skin graft(STSG)minimized scar contraction,stimulated functional neovascularization,and enhanced graft aesthetics comparable to normal skin.Remarkably,the performance of the CGL scaffold surpassed that of commercially available anti-scarring alternatives.This innovative strategy presents a straightforward approach toward scarless skin regeneration and holds promise in alleviating the prolonged,painful postoperative rehabilitation.展开更多
Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these...Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.展开更多
Crucial for mediating inflammation and the perception of pain,the ion channel known as transient receptor potential ankyrin 1(TRPA1)holds significant importance.It contributes to the increased production of cytokines ...Crucial for mediating inflammation and the perception of pain,the ion channel known as transient receptor potential ankyrin 1(TRPA1)holds significant importance.It contributes to the increased production of cytokines in the inflammatory cells of cartilage affected by osteoarthritis and represents a promising target for the treatment of this condition.By leveraging the unique advantages of liposomes,a composite microsphere drug delivery system with stable structural properties and high adaptability can be developed,providing a new strategy for osteoarthritis(OA)drug therapy.The liposomes as drug reservoirs for TRPA1 inhibitors were loaded into hyaluronic acid methacrylate(HAMA)hydrogels to make hydrogel microspheres via microfluidic technology.An in vitro inflammatory chondrocyte model was established with interleukin-1β(IL-1β)to demonstrate HAMA@Lipo@HC’s capabilities.A destabilization of the medial meniscus(DMM)mouse model was also created to evaluate the efficacy of intra-articular injections for treating OA.HAMA@Lipo@HC has a uniform particle-size distribution and is injectable.The drug encapsulation rate was 64.29%±2.58%,with a sustained release period of 28 days.Inhibition of TRPA1 via HC-030031 effectively alleviated IL-1β-induced chondrocyte inflammation and matrix degradation.In DMM model OA mice,microspheres showed good long-term sustained drug release properties,improved joint inflammation microenvironment,reduced articular cartilage damage and decreased mechanical nociceptive threshold.This research pioneers the creation of a drug delivery system tailored for delivery into the joint cavity,focusing on TRPA1 as a therapeutic target for osteoarthritis.Additionally,it offers a cutting-edge drug delivery platform aimed at addressing diseases linked to inflammation.展开更多
Vascular disrupting agents(VDAs)can destroy tumor vasculature and lead to tumor ischemia and hypoxia,resulting in tumor necrosis.However,VDAs are easy to induce the upregulation of genes that are associated with cance...Vascular disrupting agents(VDAs)can destroy tumor vasculature and lead to tumor ischemia and hypoxia,resulting in tumor necrosis.However,VDAs are easy to induce the upregulation of genes that are associated with cancer cell drug resistance and angiogenesis in tumor cells.Hypoxia-activated chemotherapy will be an ideal supplement to VDAs therapy since it can help to fully utilize the ischemia and hypoxia induced by VDAs to realize a synergistic antitumor therapeutic outcome.Here,we design a liposome whose surface is modified with a tumor-homing peptide Cys-Arg-Glu-Lys-Ala(CREKA,which can specifically target tumor vessels and stroma)and whose aqueous cavity and lipid bilayer are loaded by a hypoxia-activatable drug banoxantrone dihydrochloride(AQ4N)and a VDA combretastatin A4(CA4),respectively.CA4 can selectively target vascular endothelial cells and destroy the tumor blood vessels,which will cause the rapid inhibition of blood flow in tumor and enhance the hypoxia in the tumor region.As a consequence,AQ4N can exert its boosted cytotoxicity under the enhanced hypoxic environment.The as-prepared liposome with a uniform particle size exhibits good stability and high cancer cell killing efficacy in vitro.In addition,in vivo experiments confirm the excellent tumortargeting/accumulation,tumor vasculature-damaging,and tumor inhibition effects of the liposome.This work develops a liposomal which can achieve safe and effective tumor suppression without external stimulus excitation by only single injection,and is expected to benefit the future development of effective antitumor liposomal drugs.展开更多
Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffol...Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffold with biological function and biomimetic structure is the key to achieving a high-quality repair effect.Herein,a natural polymer-based bilayer scaffold with a porous architecture similar to that of osteochondral tissue is designed,involving the transforming growth factor-beta3-liposome-loaded upper layer for superficial cartilage regeneration and the nanohydroxyapatite-coated lower layer for subchondral bone rehabilitation.This research is conducted to evaluate the effects of nanoparticle-modified bilayer scaffold to mimic the hierarchical pro-chondrogenic and proosteogenic microenvironment for the recruited endogenous bone marrow mesenchymal stem cells.The fabricated composites were evaluated for mechanical,physicochemical,biological properties,in vitro and in vivo tissue regeneration potential.Overall,the current bilayer scaffold could regenerate a cartilage-bone integrated tissue with a seamless interfacial integration and exhibited superior tissue repair outcomes compared to other single layer scaffolds based on morphological,radiological and histological evaluation,verifying that this novel graft could be an effective approach to tissue-engineered analogs of cartilage-subchondral bone and offer new therapeutic opportunities for osteochondral defect-associated diseases.展开更多
Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to ...Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to serious consequences,including blood-brain barrier disruption and vascular aging.The Kelch-like ECH-associated protein 1(KEAP1),is a key switch of antioxidative system in human body.Until now,there is still a lack of effective treatment to ischemic stroke.Methods:We developed scutellarin-based liposomes for treating ischemic stroke injury caused neuronal damage.Results:The results showed that scutellarin could directly bind to KEAP1 protein,and the Kd was 26.1μM.The scutellarin-based liposomes significantly reduced cellular reactive oxygen species(ROS)levels.It could also upregulate the protein expression level of nuclear factor E2-related factor 2(NRF2),which is the substrate protein of KEAP1.Next,both the mRNA and protein expression level of the NRF2 downstream anti-oxidative element,heme oxygenase 1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)were promoted.Furthermore,the coimmunoprecipitation(Co-IP)and hydrogen-deuterium exchange mass spectrometry(HDX-MS)revealed that scutellarin directly bound to KEAP1’s Kelch domain,interrupting the interaction between KEAP1 and NRF2.Conclusion:Our work indicates that the scutellarin-based liposomes might be a promising therapeutic approach for ischemic stroke induced neuronal necrosis.展开更多
Objective:This study aimed to prepare doxorubicin hydrochloride liposomes and explore their application value in patients with liver cancer.Methods:Doxorubicin hydrochloride liposomes were prepared using the ammonium ...Objective:This study aimed to prepare doxorubicin hydrochloride liposomes and explore their application value in patients with liver cancer.Methods:Doxorubicin hydrochloride liposomes were prepared using the ammonium sulfate gradient method.Doxorubicin,as a broad-spectrum antitumor drug,has significant toxic and side effects after toxicological investigation.After preparing DOX-Lip,single-factor analysis was used to analyze the effects of solution pH,number of ultrafiltration,oil-water ratio,incubation temperature,and time on the encapsulation efficiency of doxorubicin hydrochloride liposomes.The process was optimized through orthogonal experiments and then applied clinically.110 patients with liver cancer were selected as the research subjects to verify the drug’s effectiveness.Results:The results of this study showed that under optimal process conditions,the prepared doxorubicin hydrochloride liposomes were evenly distributed,similar to spherical shapes,with an average particle size of 85–87 mm and a Zeta potential of 15–16 mV,indicating good encapsulation efficiency.The application of these liposomes to clinical treatment of liver cancer demonstrated good therapeutic effects and could effectively promote favorable patient prognosis.Conclusion:The doxorubicin hydrochloride liposomes prepared through process optimization exhibit strong stability and pronounced sustained-release characteristics,providing a solid foundation for the treatment of liver cancer.展开更多
As PEGylated liposomes have witnessed remarkable advancements in drug delivery,their immunogenicity has emerged as a notable challenge.In this study,we discovered that a simple pre-injection of folic acid(FA)effective...As PEGylated liposomes have witnessed remarkable advancements in drug delivery,their immunogenicity has emerged as a notable challenge.In this study,we discovered that a simple pre-injection of folic acid(FA)effectively mitigated the immunogenicity of PEGylated liposomes and enhanced their in vivo performance by tolerating splenic marginal zone B cells.FA specifically inhibited the internalization of PEGylated liposomes by splenic marginal zone B cells,thereby reducing splenic lymphocyte proliferation and specific IgM secretion.This modulation alleviated Ig M-mediated accelerated blood clearance and adverse accumulation of the PEGylated liposomes in the skin.These findings provide new insights into the immunomodulatory effects of FA and promising avenues to enhance the efficacy and safety of PEGylated liposomal nanomedicines.展开更多
Reconstituting membrane proteins in liposomes and determining their structure is a common method for determining membrane protein structures using single-particle cryo-electron microscopy(cryo-EM).However,the strong s...Reconstituting membrane proteins in liposomes and determining their structure is a common method for determining membrane protein structures using single-particle cryo-electron microscopy(cryo-EM).However,the strong signal of liposomes under cryo-EM imaging conditions often interferes with the structural determination of the embedded membrane proteins.Here,we propose a liposome signal subtraction method based on single-particle two-dimensional(2D)classification average images,aimed at enhancing the reconstruction resolution of membrane proteins.We analyzed the signal distribution characteristics of liposomes and proteins within the 2D classification average images of protein–liposome complexes in the frequency domain.Based on this analysis,we designed a method to subtract the liposome signals from the original particle images.After the subtraction,the accuracy of single-particle three-dimensional(3D)alignment was improved,enhancing the resolution of the final 3D reconstruction.We demonstrated this method using a PIEZO1-proteoliposome dataset by improving the resolution of the PIEZO1 protein.展开更多
Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all organisms.Due to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-deriv...Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all organisms.Due to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-derived drug delivery carriers have experienced explosive growth over the past decades.However,issues such as insufficient loading efficiency,heterogeneous delivery efficiency,uncontrollable targeting ability,and low production limit their wide application.Recently,the emerging exosome-liposome fusion strategy has become a potential approach to solve such issues.Thus,this review mainly focuses on the currently developed exosome-liposome fusion strategy and their application in drug delivery as well as disease treatment.This review aims to shed light on the advantages of fusion strategy in drug delivery and provides a better understanding for more rational design.The current challenge and future perspective regarding their clinical translation and application will also be discussed.展开更多
Inflammatory bowel disease (IBD) is a refractory chronic intestinal inflammatory disease caused by a malfunction of immune system. As the key immune cells in the intestine, macrophages play an important role in mainta...Inflammatory bowel disease (IBD) is a refractory chronic intestinal inflammatory disease caused by a malfunction of immune system. As the key immune cells in the intestine, macrophages play an important role in maintaining intestinal homeostasis and tissue repair of the IBD. Pharmacological modulation of macrophage function exhibits the promising therapeutic effect for IBD. In this study, mannose-modified liposomes (MAN-LPs) are prepared for macrophage targeting to improve therapeutic efficiency. Rosiglitazone (ROSI) as an agonist of peroxisome proliferators-activated receptor γ (PPAR-γ) is used as the model drug to fabricate different sized liposomes. The impacts of mannose modification and particle size for macrophage targeting are investigated in cells, zebrafish, and mouse models and the therapeutic effects of the MAN-LPs are evaluated on dextran sulfate sodium (DSS)-induced IBD mouse. Compared to unmodified liposome, MAN-LPs display higher uptake by RAW 264.7 cells and better co-localization with macrophage in zebrafish model. Furthermore, MAN-LPs could effectively accumulate in the inflammatory intestinal sites in IBD mouse model. Most importantly, the targeting ability of MAN-LPs is obviously enhanced with the increasing of particle size, whereas the largest MAN-LPs particles achieve the best anti-inflammatory effect in cells, and a higher therapeutic efficiency in IBD mouse model. Therefore, mannose-modified liposome is a promising strategy for macrophage-targeting in IBD treatment. Particle size of MAN-LPs will affect macrophage targeting ability, as well as the therapeutic effect in-vivo.展开更多
Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor reg...Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.展开更多
Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising i...Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.展开更多
Pterostilbene(PT),a lipid-soluble polyphenol known for its antioxidant,anticancer,and various other biological properties,holds potential as an active ingredient in cosmetics for its anti-wrinkle and skin-whitening ef...Pterostilbene(PT),a lipid-soluble polyphenol known for its antioxidant,anticancer,and various other biological properties,holds potential as an active ingredient in cosmetics for its anti-wrinkle and skin-whitening effects.However,its application is limited by its low water solubility and poor penetration through the stratum corneum.To address these limitations,this study initially prepared Pterostilbene nanoliposomes(PT-NLPs)using a high shear-microjet homogenization treatment method,because of the distinctive hydrophilic and hydrophilic properties of the liposomes.The stability under different storage conditions of the PT-NLPs was evaluated by investigating the alterations of the particle size,PDI,Zeta potential and surface morphology,combined with the test results of Lumisizer stability analyzer.Finally,the comprehensive performance of PT-NLPs was evaluated through in vitro dermal and transdermal testing,human testing,and instrument testing.The results showed that the PT-NLPs treated by the high shear-microjet homogenisation method proposed in this paper possessed a 1.7-fold increase in the retention performance compared with the free PT solution,and no penetration occurred on the blood-brain barrier,indicating that PT-NLPs would not cause toxicity to the organism.The human efficacy evaluation found that the PT-NLPs whitening serum could improve skin dullness,brighten skin tone,and improve skin sensitivity after 14 days of use.The high shear-microjet homogenisation method proposed in this paper for the treatment of PT-NLPs improved the transdermal delivery properties of PT.The process has a broad application prospect in the fields of medicine and cosmetics.展开更多
We summarize the mechanism by which taurine(Tau)inhibits autophagy and induces iron apoptosis in hepatic stellate cells.Tau interacts with autophagy regulates multifunctional proteins,microtubule-associated protein 1 ...We summarize the mechanism by which taurine(Tau)inhibits autophagy and induces iron apoptosis in hepatic stellate cells.Tau interacts with autophagy regulates multifunctional proteins,microtubule-associated protein 1 light chain 3 Beta,and autophagy-related gene 5 to inhibit autophagy,binds to ferritin heavy chain 1 and nuclear receptor coactivator 4 to trigger ferritin autophagy,and interacts with glutathione peroxidase 4 to promote iron apoptosis.There is a solid rationale for developing Tau-based therapies targeting autophagy and ferroptosis regulation.From a pharmaceutical point of view,there are certain requirements for Tau protein delivery systems,such as loading efficiency,stability,and targeting.Nanomaterials should also contain a hydrophilic motif similar to Tau to optimize loading efficiency.Since Tau is a hydrophilic molecule with high water solubility,liposomes,micelles,and amphiphilic polymer nanoparticles may represent a superior choice.The nanostructure of the liposome includes a water region and a lipid membrane to sequester hydrophilic and hydrophobic drugs,respectively,whereas Tau is expected to be loaded into the water region.In addition,a representative method of actively targeting hematopoietic stem cells is introduced.A Tau-based method for the treatment of liver fibrosis is proposed based on the formulation of common liposomes(lecithin plus cholesterol).展开更多
Paclitaxel(PTX)is widely applied for the treatment of unresectable and metastasis breast carcinoma as well as other cancers,whereas its efficacy is always impeded by poor solubility.Liposomes are one kind of the most ...Paclitaxel(PTX)is widely applied for the treatment of unresectable and metastasis breast carcinoma as well as other cancers,whereas its efficacy is always impeded by poor solubility.Liposomes are one kind of the most successful drug carriers which are capable of solubilizing PTX and improving patients’tolerance owing to excellent biocompatibility and biodegradability.However,poor compatibility between PTX and liposomes compromises the stability,drug loading and anti-tumor capacity of liposomal formulations.To address this issue,three lipids with various chain lengths,namely,myristic acid(MA,14C),palmitic acid(PA,16C)and stearic acid(SA,18C),were conjugated to PTX via ester bonds and the synthesized prodrugs with high lipophilicity were further formulated into liposomes,respectively.All liposomes show high stability and drug loadings,as well as sustained drug release.The chain lengths of lipids are negatively correlated with drug release and enzymatic conversion rates,which further impact the pharmacokinetics,tumor accumulation,and anti-tumor efficacy of liposomal PTX.Neither rapid nor slow drug release facilitates high tumor accumulation as well as anti-tumor efficacy of PTX.Among all liposomes,PTX-PA-loaded liposomes show the longest circulation and highest tumor accumulation of PTX and exert the most potent anti-tumor capacities in vivo,owing to its moderate drug release and enzymatic conversion rate.Witnessing its superior safety,PTX-PA liposomes hold potential for further clinical translation.展开更多
Despite standard treatment for non-small cell lung cancer(NSCLC)being surgical resection,cancer recurrence and complications,such as induction of malignant pleural effusion(MPE)and significant postoperative pain,usual...Despite standard treatment for non-small cell lung cancer(NSCLC)being surgical resection,cancer recurrence and complications,such as induction of malignant pleural effusion(MPE)and significant postoperative pain,usually result in treatment failure.In this study,an alginate-based hybrid hydrogel(SOG)is developed that can be injected into the resection surface of the lungs during surgery.Briefly,endoplasmic reticulum-modified liposomes(MSLs)pre-loaded with the signal transducer and activator of transcription 3(STAT3)small interfering RNA and lidocaine hydrochloride are encapsulated in SOG.Once applied,MSLs strongly downregulated STAT3 expression in the tumor microenvironment,resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype.Meanwhile,the release of lidocaine hydrochloride(LID)was beneficial for pain relief and natural killer cell activation.Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life,including reduced MPE volume and pain relief in orthotopic NSCLC mouse models,even with a single administration.MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC,and may alter the treatment paradigms for other cancers.展开更多
基金supported by the Macao Science and Technology Development Fund (FDCT 0148/2022/A3 and 0019/2024/RIA1)the National Natural Science Foundation of China (No. 81572979)
文摘Immunotherapy with interleukin-2(IL-2)in treating cancers is subject to several limitations such as systemic side effects and reduced efficacy against tumors with low immune cell infiltration despite its promise.To address these challenges,IL-2-So-Lipo,a novel liposomal formulation combining IL-2 with sorafenib derivative,was developed as an anti-angiogenic drug that inhibits the growth of new blood vessels which play crucial roles in tumor growth.Sorafenib derivatives could target at melanoma-specific receptors,further enhancing liposomal specificity at the tumor site.Our results demonstrated that the prepared IL-2-So-Lipo significantly enhanced anti-tumor activity compared to IL-2 or sorafenib monotherapies,as well as their combination.In a B16F10 melanoma model,IL-2-So-Lipo was found to significantly inhibit tumor progression(tumor volume of 108.01±62.99 mm^(3))compared to the control group(tumor volume of 1,397.13±75.55 mm^(3)),improving the therapeutic efficacy.This enhanced efficacy is attributed to the targeted delivery of IL-2 which promoted the infiltration and activation of cytotoxic T lymphocytes.Additionally,liposomal encapsulation of sorafenib derivatives enhanced its delivery efficiency,promoting tumor cell apoptosis and suppressing angiogenesis.Mechanistically,IL-2-So-Lipo could kill tumors by inducing a shift towards an anti-tumor immune response via facilitating the polarization of macrophages towards the M1 phenotype.Furthermore,IL-2-So-Lipo downregulated several key proteins in the MAPK signaling pathway,exerting a significant role in mediating tumor resistance to sorafenib.These findings underscore the potential of IL-2-So-Lipo as a promising strategy to improve the therapeutic efficacy of immunotherapy and targeted therapy in cancers.Moreover,the combination of IL-2 and sorafenib in a liposomal delivery system overcame the limitations of conventional IL-2 therapy,offering a synergistic approach to improve therapeutic outcomes for solid tumors.
文摘Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal anti-inflammatory drugs(NSAIDs),and corticosteroids,frequently result in unintended adverse effects.Dexamethasone(DEX)is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties.Liposomal delivery of DEX,particu-larly when liposomes are surface-modified with targeting ligands like peptides or sialic acid,can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity.This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA.Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models,reduces joint inflammation and damage,and alleviates cartilage destruction compared to free DEX.The liposomal formulation also shows better hemocompatibility,fewer adverse effects on body weight and immune organ index,and a longer circulation time with higher bioavailability.The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α(TNF-α)and B-cell-activating factor(BAFF),which are key players in the pathogenesis of RA.Additionally,liposomal DEX can induce the expres-sion of anti-inflammatory cytokines like interleukin-10(IL-10),which has significant anti-inflammatory and immunoregulatory properties.The findings suggest that lipo-somal DEX represents a promising candidate for effective and safe RA therapy,with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.
基金supported by the National Key Research and Development Plan of the Ministry of Science and Technology,China(Grant No.:2022YFE0125300)the National Natural Science Foundation of China(Grant No:81690262)+2 种基金the National Science and Technology Major Project,China(Grant No.:2017ZX09201004-021)the Open Project of National facility for Translational Medicine(Shanghai),China(Grant No.:TMSK-2021-104)Shanghai Jiao Tong University STAR Grant,China(Grant Nos.:YG2022ZD024 and YG2022QN111).
文摘Liposomes serve as critical carriers for drugs and vaccines,with their biological effects influenced by their size.The microfluidic method,renowned for its precise control,reproducibility,and scalability,has been widely employed for liposome preparation.Although some studies have explored factors affecting liposomal size in microfluidic processes,most focus on small-sized liposomes,predominantly through experimental data analysis.However,the production of larger liposomes,which are equally significant,remains underexplored.In this work,we thoroughly investigate multiple variables influencing liposome size during microfluidic preparation and develop a machine learning(ML)model capable of accurately predicting liposomal size.Experimental validation was conducted using a staggered herringbone micromixer(SHM)chip.Our findings reveal that most investigated variables significantly influence liposomal size,often interrelating in complex ways.We evaluated the predictive performance of several widely-used ML algorithms,including ensemble methods,through cross-validation(CV)for both lipo-some size and polydispersity index(PDI).A standalone dataset was experimentally validated to assess the accuracy of the ML predictions,with results indicating that ensemble algorithms provided the most reliable predictions.Specifically,gradient boosting was selected for size prediction,while random forest was employed for PDI prediction.We successfully produced uniform large(600 nm)and small(100 nm)liposomes using the optimised experimental conditions derived from the ML models.In conclusion,this study presents a robust methodology that enables precise control over liposome size distribution,of-fering valuable insights for medicinal research applications.
基金supported by the National Natural Science Foundation of China(No.82272297).
文摘Abnormal wound scarring often leads to functional impairments and cosmetic deformities,primarily driven by the prolonged activation of the TGF-β/Smad signaling pathway.Addressing this challenge,we developed a biomimetic scaffold aimed at facilitating rapid and scarless wound healing.This highly in-tegrated 3D-printed dermal scaffold comprised modified recombinant human type III collagen(rhCOLIII-MA),gelatin methacrylate(GelMA),and liposomes encapsulating SB431542 to target TGF-β1(Lip@SB).The rhCOLIII-MA/GelMA(CG)scaffold retained inherent biomaterial characteristics,exhibited tailored physicochemical properties,and demonstrated favorable biocompatibility.Moreover,the Lip@SB-loaded CG scaffold(CGL)effectively promoted in vitro wound healing,while enabling controlled release of SB431542 to inhibit pathological collagen deposition.In a full-thickness skin defect rat model,the CGL dermal scaffold combined with split-thickness skin graft(STSG)minimized scar contraction,stimulated functional neovascularization,and enhanced graft aesthetics comparable to normal skin.Remarkably,the performance of the CGL scaffold surpassed that of commercially available anti-scarring alternatives.This innovative strategy presents a straightforward approach toward scarless skin regeneration and holds promise in alleviating the prolonged,painful postoperative rehabilitation.
基金supported by the National Natural Science Foundation of China, Nos. 82271411 (to RG), 51803072 (to WLiu)grants from the Department of Finance of Jilin Province, Nos. 2022SCZ25 (to RG), 2022SCZ10 (to WLiu), 2021SCZ07 (to RG)+2 种基金Jilin Provincial Science and Technology Program, No. YDZJ202201ZYTS038 (to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University, No. 2022qnpy11 (to WLuo)The Project of China-Japan Union Hospital of Jilin University, No. XHQMX20233 (to RG)
文摘Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.
基金supported by the National Key Research and Development Program of China(No.82230071)National Natural Science Foundation of China(Nos.82202674,82202334)Wenzhou Science and Technology Project(Nos.Y20220178,Y20220016).
文摘Crucial for mediating inflammation and the perception of pain,the ion channel known as transient receptor potential ankyrin 1(TRPA1)holds significant importance.It contributes to the increased production of cytokines in the inflammatory cells of cartilage affected by osteoarthritis and represents a promising target for the treatment of this condition.By leveraging the unique advantages of liposomes,a composite microsphere drug delivery system with stable structural properties and high adaptability can be developed,providing a new strategy for osteoarthritis(OA)drug therapy.The liposomes as drug reservoirs for TRPA1 inhibitors were loaded into hyaluronic acid methacrylate(HAMA)hydrogels to make hydrogel microspheres via microfluidic technology.An in vitro inflammatory chondrocyte model was established with interleukin-1β(IL-1β)to demonstrate HAMA@Lipo@HC’s capabilities.A destabilization of the medial meniscus(DMM)mouse model was also created to evaluate the efficacy of intra-articular injections for treating OA.HAMA@Lipo@HC has a uniform particle-size distribution and is injectable.The drug encapsulation rate was 64.29%±2.58%,with a sustained release period of 28 days.Inhibition of TRPA1 via HC-030031 effectively alleviated IL-1β-induced chondrocyte inflammation and matrix degradation.In DMM model OA mice,microspheres showed good long-term sustained drug release properties,improved joint inflammation microenvironment,reduced articular cartilage damage and decreased mechanical nociceptive threshold.This research pioneers the creation of a drug delivery system tailored for delivery into the joint cavity,focusing on TRPA1 as a therapeutic target for osteoarthritis.Additionally,it offers a cutting-edge drug delivery platform aimed at addressing diseases linked to inflammation.
基金supported by the Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University),Ministry of Education(No.GKE-KF202305)the Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor,and the Natural Science Foundation of Jiangsu Province(No.BK20211510)。
文摘Vascular disrupting agents(VDAs)can destroy tumor vasculature and lead to tumor ischemia and hypoxia,resulting in tumor necrosis.However,VDAs are easy to induce the upregulation of genes that are associated with cancer cell drug resistance and angiogenesis in tumor cells.Hypoxia-activated chemotherapy will be an ideal supplement to VDAs therapy since it can help to fully utilize the ischemia and hypoxia induced by VDAs to realize a synergistic antitumor therapeutic outcome.Here,we design a liposome whose surface is modified with a tumor-homing peptide Cys-Arg-Glu-Lys-Ala(CREKA,which can specifically target tumor vessels and stroma)and whose aqueous cavity and lipid bilayer are loaded by a hypoxia-activatable drug banoxantrone dihydrochloride(AQ4N)and a VDA combretastatin A4(CA4),respectively.CA4 can selectively target vascular endothelial cells and destroy the tumor blood vessels,which will cause the rapid inhibition of blood flow in tumor and enhance the hypoxia in the tumor region.As a consequence,AQ4N can exert its boosted cytotoxicity under the enhanced hypoxic environment.The as-prepared liposome with a uniform particle size exhibits good stability and high cancer cell killing efficacy in vitro.In addition,in vivo experiments confirm the excellent tumortargeting/accumulation,tumor vasculature-damaging,and tumor inhibition effects of the liposome.This work develops a liposomal which can achieve safe and effective tumor suppression without external stimulus excitation by only single injection,and is expected to benefit the future development of effective antitumor liposomal drugs.
基金supported by grants from the China Postdoctoral Science Foundation(Nos.2022TQ0397,2022MD723744,2022M710564,2022M720603)Natural Science Foundation of China(Nos.82272553,82102571,81974346,8210257,82472404)+8 种基金Chongqing Municipal Medical Youth Talent Support Program,Chongqing,China(No.YXQN202408)Natural Science Foundation of Chongqing,China(Nos.CSTB2022NSCQ-MSX0089,CSTB2022NSCQ-MSX0104,CSTB2024NSCQMSX0532)Joint Medical Research Project of Health Commission&Science and Technology Bureau of Chongqing,China(No.2024QNXM032)Special Project for the Central Government to Guide the Development of Local Science and Technology in Sichuan Province(No.2023ZYD0071)National Natural Science Foundation of Sichuan(No.24NSFSC1274)Project of Innovative Science Research for Postgraduate of Chongqing Municipal Education Committee,Chongqing,China(Nos.CYS22389,CYB240224)National Natural Science Foundation of Sichuan(No.2024NSFSC0678)Research Project of the Affiliated Hospital of North Sichuan Medical College(Nos.2023ZD002,2023-2ZD001,2024JB001)Disciplines Construction Program of The Third Affiliated Hospital of Chongqing Medical University(Nos.KY23035,KY23041).
文摘Osteochondral defects pose an enormous challenge,and no satisfactory therapy is available to date due to the hierarchy of the native tissue consisting of articular cartilage and subchondral bone.Constructing a scaffold with biological function and biomimetic structure is the key to achieving a high-quality repair effect.Herein,a natural polymer-based bilayer scaffold with a porous architecture similar to that of osteochondral tissue is designed,involving the transforming growth factor-beta3-liposome-loaded upper layer for superficial cartilage regeneration and the nanohydroxyapatite-coated lower layer for subchondral bone rehabilitation.This research is conducted to evaluate the effects of nanoparticle-modified bilayer scaffold to mimic the hierarchical pro-chondrogenic and proosteogenic microenvironment for the recruited endogenous bone marrow mesenchymal stem cells.The fabricated composites were evaluated for mechanical,physicochemical,biological properties,in vitro and in vivo tissue regeneration potential.Overall,the current bilayer scaffold could regenerate a cartilage-bone integrated tissue with a seamless interfacial integration and exhibited superior tissue repair outcomes compared to other single layer scaffolds based on morphological,radiological and histological evaluation,verifying that this novel graft could be an effective approach to tissue-engineered analogs of cartilage-subchondral bone and offer new therapeutic opportunities for osteochondral defect-associated diseases.
文摘Background:Ischemic stroke is a disease characterized by the damage of brain tissue due to insufficient blood supply.The neuronal necrosis caused by oxidative stress during the acute phase of ischemic stroke leads to serious consequences,including blood-brain barrier disruption and vascular aging.The Kelch-like ECH-associated protein 1(KEAP1),is a key switch of antioxidative system in human body.Until now,there is still a lack of effective treatment to ischemic stroke.Methods:We developed scutellarin-based liposomes for treating ischemic stroke injury caused neuronal damage.Results:The results showed that scutellarin could directly bind to KEAP1 protein,and the Kd was 26.1μM.The scutellarin-based liposomes significantly reduced cellular reactive oxygen species(ROS)levels.It could also upregulate the protein expression level of nuclear factor E2-related factor 2(NRF2),which is the substrate protein of KEAP1.Next,both the mRNA and protein expression level of the NRF2 downstream anti-oxidative element,heme oxygenase 1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)were promoted.Furthermore,the coimmunoprecipitation(Co-IP)and hydrogen-deuterium exchange mass spectrometry(HDX-MS)revealed that scutellarin directly bound to KEAP1’s Kelch domain,interrupting the interaction between KEAP1 and NRF2.Conclusion:Our work indicates that the scutellarin-based liposomes might be a promising therapeutic approach for ischemic stroke induced neuronal necrosis.
文摘Objective:This study aimed to prepare doxorubicin hydrochloride liposomes and explore their application value in patients with liver cancer.Methods:Doxorubicin hydrochloride liposomes were prepared using the ammonium sulfate gradient method.Doxorubicin,as a broad-spectrum antitumor drug,has significant toxic and side effects after toxicological investigation.After preparing DOX-Lip,single-factor analysis was used to analyze the effects of solution pH,number of ultrafiltration,oil-water ratio,incubation temperature,and time on the encapsulation efficiency of doxorubicin hydrochloride liposomes.The process was optimized through orthogonal experiments and then applied clinically.110 patients with liver cancer were selected as the research subjects to verify the drug’s effectiveness.Results:The results of this study showed that under optimal process conditions,the prepared doxorubicin hydrochloride liposomes were evenly distributed,similar to spherical shapes,with an average particle size of 85–87 mm and a Zeta potential of 15–16 mV,indicating good encapsulation efficiency.The application of these liposomes to clinical treatment of liver cancer demonstrated good therapeutic effects and could effectively promote favorable patient prognosis.Conclusion:The doxorubicin hydrochloride liposomes prepared through process optimization exhibit strong stability and pronounced sustained-release characteristics,providing a solid foundation for the treatment of liver cancer.
基金supported by the National Natural Science Foundation of China(Nos.82373817 and 82003659)Shanghai Natural Science Foundation(No.23ZR1477500)Pudong Health Bureau of Shanghai(No.YC-2023-0401)。
文摘As PEGylated liposomes have witnessed remarkable advancements in drug delivery,their immunogenicity has emerged as a notable challenge.In this study,we discovered that a simple pre-injection of folic acid(FA)effectively mitigated the immunogenicity of PEGylated liposomes and enhanced their in vivo performance by tolerating splenic marginal zone B cells.FA specifically inhibited the internalization of PEGylated liposomes by splenic marginal zone B cells,thereby reducing splenic lymphocyte proliferation and specific IgM secretion.This modulation alleviated Ig M-mediated accelerated blood clearance and adverse accumulation of the PEGylated liposomes in the skin.These findings provide new insights into the immunomodulatory effects of FA and promising avenues to enhance the efficacy and safety of PEGylated liposomal nanomedicines.
基金Project supported by the National Natural Science Foundation of China (Grant Nos.32241023 and 92254306)the Fund from the Tsinghua–Peking Joint Center for Life SciencesBeijing Frontier Research Center for Biological Structure。
文摘Reconstituting membrane proteins in liposomes and determining their structure is a common method for determining membrane protein structures using single-particle cryo-electron microscopy(cryo-EM).However,the strong signal of liposomes under cryo-EM imaging conditions often interferes with the structural determination of the embedded membrane proteins.Here,we propose a liposome signal subtraction method based on single-particle two-dimensional(2D)classification average images,aimed at enhancing the reconstruction resolution of membrane proteins.We analyzed the signal distribution characteristics of liposomes and proteins within the 2D classification average images of protein–liposome complexes in the frequency domain.Based on this analysis,we designed a method to subtract the liposome signals from the original particle images.After the subtraction,the accuracy of single-particle three-dimensional(3D)alignment was improved,enhancing the resolution of the final 3D reconstruction.We demonstrated this method using a PIEZO1-proteoliposome dataset by improving the resolution of the PIEZO1 protein.
基金supported by the National Key Research&Development Program of China(Nos.2021YFC2302400,2021YFA1201000,2021YFE0106900)the National Natural Science Foundation of China(Nos.32171394,32101148,82202338)+2 种基金the Beijing Nova Program(Interdisciplinary Cooperation Project)from Beijing Municipal Science&Technology Commission(No.20220484207)the Beijing Natural Science Foundation(No.L222128)the Fundamental Research Funds for the Central Universities(No.2022CX01013).
文摘Exosomes are membrane-bound nanoscale extracellular vesicles,which produced by almost all organisms.Due to the excellent biocompatibility,long circulation time as well as low immunogenicity,exosomes as naturally-derived drug delivery carriers have experienced explosive growth over the past decades.However,issues such as insufficient loading efficiency,heterogeneous delivery efficiency,uncontrollable targeting ability,and low production limit their wide application.Recently,the emerging exosome-liposome fusion strategy has become a potential approach to solve such issues.Thus,this review mainly focuses on the currently developed exosome-liposome fusion strategy and their application in drug delivery as well as disease treatment.This review aims to shed light on the advantages of fusion strategy in drug delivery and provides a better understanding for more rational design.The current challenge and future perspective regarding their clinical translation and application will also be discussed.
基金the Macao Science and Technology Development Fund(No.0086/2021/A2)Shenzhen Fundamental Research Program(No.SGDX20210823103804030)+1 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab,No.2020B1212030006)Guangdong Basic and Applied Basic Research Foundation(No.2022A1515012416).
文摘Inflammatory bowel disease (IBD) is a refractory chronic intestinal inflammatory disease caused by a malfunction of immune system. As the key immune cells in the intestine, macrophages play an important role in maintaining intestinal homeostasis and tissue repair of the IBD. Pharmacological modulation of macrophage function exhibits the promising therapeutic effect for IBD. In this study, mannose-modified liposomes (MAN-LPs) are prepared for macrophage targeting to improve therapeutic efficiency. Rosiglitazone (ROSI) as an agonist of peroxisome proliferators-activated receptor γ (PPAR-γ) is used as the model drug to fabricate different sized liposomes. The impacts of mannose modification and particle size for macrophage targeting are investigated in cells, zebrafish, and mouse models and the therapeutic effects of the MAN-LPs are evaluated on dextran sulfate sodium (DSS)-induced IBD mouse. Compared to unmodified liposome, MAN-LPs display higher uptake by RAW 264.7 cells and better co-localization with macrophage in zebrafish model. Furthermore, MAN-LPs could effectively accumulate in the inflammatory intestinal sites in IBD mouse model. Most importantly, the targeting ability of MAN-LPs is obviously enhanced with the increasing of particle size, whereas the largest MAN-LPs particles achieve the best anti-inflammatory effect in cells, and a higher therapeutic efficiency in IBD mouse model. Therefore, mannose-modified liposome is a promising strategy for macrophage-targeting in IBD treatment. Particle size of MAN-LPs will affect macrophage targeting ability, as well as the therapeutic effect in-vivo.
基金funding from the Liaoning Province Doctoral Start-up(grant number 2023-BS-086).
文摘Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.
基金funded by the Optimization Study of Treatment Regimen and Clinical Practice in Ovarian Cancer(grant number:2016YFC1303702).
文摘Background:The paclitaxel liposome formulation,encapsulating paclitaxel within a phospholipid bilayer,ad-dresses the insolubility of traditional paclitaxel formulations,thereby reducing toxicity without compromising its antitumor efficacy.Methods:This multicenter,open-label,non-inferiority randomized controlled trial(ChiCTR2000038555)evalu-ates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin(PLC vs.PC)as first-line therapy in patients with epithelial ovarian cancer.Results:An analysis of median progression-free survival(PFS)revealed non-inferior outcomes between 263 pa-tients in the PLC group and 260 patients in the PC group(32.3 vs.29.9 months,hazard ratio[HR],0.89[95%CI,0.64−1.25]),using a non-inferior margin of 1.3.Although the overall incidence of treatment-related adverse events was comparable between groups,the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen.Conclusion:The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of pa-clitaxel and carboplatin regarding therapeutic efficacy,with an enhanced safety profile marked by reduced non-hematologic toxicities.
基金supported by the Guangdong Provincial University Key Area Project[grant numbers 2023ZDZX4136]the Guangdong Provincial University Innovation Team Project[grant numbers 2023KCXTD085]+1 种基金the Guangdong Provincial Science and Technology Innovation Strategy Special Fund[grant numbers pdjh2022b1046]the Student Scientific Research Project of Jiangmen Polytechnic[grant numbers jzxsky20230102]。
文摘Pterostilbene(PT),a lipid-soluble polyphenol known for its antioxidant,anticancer,and various other biological properties,holds potential as an active ingredient in cosmetics for its anti-wrinkle and skin-whitening effects.However,its application is limited by its low water solubility and poor penetration through the stratum corneum.To address these limitations,this study initially prepared Pterostilbene nanoliposomes(PT-NLPs)using a high shear-microjet homogenization treatment method,because of the distinctive hydrophilic and hydrophilic properties of the liposomes.The stability under different storage conditions of the PT-NLPs was evaluated by investigating the alterations of the particle size,PDI,Zeta potential and surface morphology,combined with the test results of Lumisizer stability analyzer.Finally,the comprehensive performance of PT-NLPs was evaluated through in vitro dermal and transdermal testing,human testing,and instrument testing.The results showed that the PT-NLPs treated by the high shear-microjet homogenisation method proposed in this paper possessed a 1.7-fold increase in the retention performance compared with the free PT solution,and no penetration occurred on the blood-brain barrier,indicating that PT-NLPs would not cause toxicity to the organism.The human efficacy evaluation found that the PT-NLPs whitening serum could improve skin dullness,brighten skin tone,and improve skin sensitivity after 14 days of use.The high shear-microjet homogenisation method proposed in this paper for the treatment of PT-NLPs improved the transdermal delivery properties of PT.The process has a broad application prospect in the fields of medicine and cosmetics.
基金Supported by the National Natural Science Foundation of China,No.82373800Guangdong Basic and Applied Basic Research Foundation,No.2024A1515011236General Program of Administration of Traditional Chinese Medicine of Guangdong Province,No.20241071.
文摘We summarize the mechanism by which taurine(Tau)inhibits autophagy and induces iron apoptosis in hepatic stellate cells.Tau interacts with autophagy regulates multifunctional proteins,microtubule-associated protein 1 light chain 3 Beta,and autophagy-related gene 5 to inhibit autophagy,binds to ferritin heavy chain 1 and nuclear receptor coactivator 4 to trigger ferritin autophagy,and interacts with glutathione peroxidase 4 to promote iron apoptosis.There is a solid rationale for developing Tau-based therapies targeting autophagy and ferroptosis regulation.From a pharmaceutical point of view,there are certain requirements for Tau protein delivery systems,such as loading efficiency,stability,and targeting.Nanomaterials should also contain a hydrophilic motif similar to Tau to optimize loading efficiency.Since Tau is a hydrophilic molecule with high water solubility,liposomes,micelles,and amphiphilic polymer nanoparticles may represent a superior choice.The nanostructure of the liposome includes a water region and a lipid membrane to sequester hydrophilic and hydrophobic drugs,respectively,whereas Tau is expected to be loaded into the water region.In addition,a representative method of actively targeting hematopoietic stem cells is introduced.A Tau-based method for the treatment of liver fibrosis is proposed based on the formulation of common liposomes(lecithin plus cholesterol).
基金supported by National Natural Science Foundation of China(Nos.82273867,82030107)Shanghai Science and Technology Project of Little Giant(No.1902HX76600)+1 种基金Shanghai Qingpu District Industry-University-Research Cooperative Development Funding Project(No.2022-7)High-level Talents of Fujian University of Chinese Medicine(No.X2019006-Talents).
文摘Paclitaxel(PTX)is widely applied for the treatment of unresectable and metastasis breast carcinoma as well as other cancers,whereas its efficacy is always impeded by poor solubility.Liposomes are one kind of the most successful drug carriers which are capable of solubilizing PTX and improving patients’tolerance owing to excellent biocompatibility and biodegradability.However,poor compatibility between PTX and liposomes compromises the stability,drug loading and anti-tumor capacity of liposomal formulations.To address this issue,three lipids with various chain lengths,namely,myristic acid(MA,14C),palmitic acid(PA,16C)and stearic acid(SA,18C),were conjugated to PTX via ester bonds and the synthesized prodrugs with high lipophilicity were further formulated into liposomes,respectively.All liposomes show high stability and drug loadings,as well as sustained drug release.The chain lengths of lipids are negatively correlated with drug release and enzymatic conversion rates,which further impact the pharmacokinetics,tumor accumulation,and anti-tumor efficacy of liposomal PTX.Neither rapid nor slow drug release facilitates high tumor accumulation as well as anti-tumor efficacy of PTX.Among all liposomes,PTX-PA-loaded liposomes show the longest circulation and highest tumor accumulation of PTX and exert the most potent anti-tumor capacities in vivo,owing to its moderate drug release and enzymatic conversion rate.Witnessing its superior safety,PTX-PA liposomes hold potential for further clinical translation.
基金supported by the National Natural Science Foundation of China[grant numbers 21873057,22373059]the Natural Science Foundation of Shandong Province[grant numbers ZR2023MB082]。
文摘Despite standard treatment for non-small cell lung cancer(NSCLC)being surgical resection,cancer recurrence and complications,such as induction of malignant pleural effusion(MPE)and significant postoperative pain,usually result in treatment failure.In this study,an alginate-based hybrid hydrogel(SOG)is developed that can be injected into the resection surface of the lungs during surgery.Briefly,endoplasmic reticulum-modified liposomes(MSLs)pre-loaded with the signal transducer and activator of transcription 3(STAT3)small interfering RNA and lidocaine hydrochloride are encapsulated in SOG.Once applied,MSLs strongly downregulated STAT3 expression in the tumor microenvironment,resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype.Meanwhile,the release of lidocaine hydrochloride(LID)was beneficial for pain relief and natural killer cell activation.Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life,including reduced MPE volume and pain relief in orthotopic NSCLC mouse models,even with a single administration.MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC,and may alter the treatment paradigms for other cancers.
