Diabetic macular edema(DME)is a very important and well-known cause of visual loss in diabetics.Blood-retina barrier disruption and consequent intraretinal fluid accumulation may lead to retinal thickening at the post...Diabetic macular edema(DME)is a very important and well-known cause of visual loss in diabetics.Blood-retina barrier disruption and consequent intraretinal fluid accumulation may lead to retinal thickening at the posterior pole namely DME.Even though it is not clearly understood,current evidence suggests that chronic low-grade inflammation characterized with various cytokines has a major role in the occurrence of DME.Clinical trials are continuously shaping our treatment approaches for the eyes with DME.Today,vascular endothelial growth factor(VEGF)inhibitor and steroid administrations are the main alternatives in DME treatment.Dexamethasone(DEX)implant(Ozurdex®;Allergan,Inc.,Irvine,CA,United States)was approved by the United States Food&Drug Administration in 2014 for DME treatment.The implant is made up of a biodegradable solid copolymer that is broken down by releasing its active ingredient into the vitreous cavity over time.Biphasic release feature of this sustained-release drug delivery system ensures its efficacy for up to 6 mo with an acceptable and manageable safety profile.DEX implant provides a favorable anatomical and functional outcome in DME as shown in several randomized-controlled studies but has a relatively higher ocular side-effect profile such as increased risk of cataract formation and raised intraocular pressure when compared to the gold standard anti-VEGF agents.Thus,DEX implant becomes the second-line treatment option demonstrating inadequate clinical response to anti-VEGF therapy.However,it can be preferred as the first-line treatment in vitrectomized and pseudophakic eyes.Even in some selected conditions DEX implant is favored over anti-VEGF agents where the use of VEGF-inhibitors is either inappropriate or contraindicated such as the patients with a recent history of a major cardiovascular or cerebrovascular event,pregnancy and noncompliant to frequent visits.This mini-review briefly overviews the efficacy,safety profile and complications of DEX implant and summarizes the outcome of DEX implant administration in major clinical studies on DME treatment.展开更多
Extracellular vesicles(EVs)are crucial for facilitating intercellular communication,promoting cell migration,and orchestrating the immune response.Recently,EVs can diagnose and treat tumors.EVs can be measured as biom...Extracellular vesicles(EVs)are crucial for facilitating intercellular communication,promoting cell migration,and orchestrating the immune response.Recently,EVs can diagnose and treat tumors.EVs can be measured as biomarkers to provide information about the type of disease and therapeutic efficacy.Furthermore,EVs with lower immunogenicity and better biocompatibility are natural carriers of chemicals and gene drugs.Herein,we review the molecular composition,biogenesis,and separation methods of EVs.We also highlight the important role of EVs from different origins as biomarkers and drug delivery systems in tumor therapy.Finally,we provide deep insights into how EVs play a role in reversing the immunosuppressive microenvironment.展开更多
Intravesical drug delivery(IDD),as a noninvasive,local pathway of administration,has great clinical significance for bladder diseases,especially bladder cancer.Despite the many advantages of IDD such as enhanced focal...Intravesical drug delivery(IDD),as a noninvasive,local pathway of administration,has great clinical significance for bladder diseases,especially bladder cancer.Despite the many advantages of IDD such as enhanced focal drug exposure and avoidance of systemic adverse drug reactions,the effectiveness of drug delivery is greatly challenged by the physiological barriers of the bladder.In this review,the routes and barriers encountered in IDD are first discussed,and attention is paid to the potential internal/mucosal retention and absorption-transport mechanisms of drugs.On this basis,the avoidance,overcoming and utilization of the"three barriers"is further emphasized,and current design and fabrication strategies for intravesical drug delivery systems(IDDSs)are described mainly from the perspectives of constructing drug reservoirs,enhancing permeability and targeting,with the hope of providing systematic understanding and inspirations for the research of novel IDDSs and their treatment of bladder diseases.展开更多
High glucose level, bacterial infection, and persistent inflammation within the microenvironment are key factors contributing to the delay of diabetic ulcers healing, while traditional therapeutic methods generally fa...High glucose level, bacterial infection, and persistent inflammation within the microenvironment are key factors contributing to the delay of diabetic ulcers healing, while traditional therapeutic methods generally fail to address these issues simultaneously. Here, we present a spatiotemporally responsive cascade bilayer microneedle (MN) patch for accelerating diabetic wound healing via local glucose depletion and sustained nitric oxide (NO) release for long-term antibacterial and anti-inflammatory effects. The MN patch (G/AZ-MNs) possesses a degradable tip layer loading glucose oxidase (GOx), as well as a dissolvable base layer encapsulating l-arginine (Arg)-loaded nanoparticles (NPs). After wound administration, the base part rapidly dissolved, resulting in prompt separation of the MN tip within the wound tissue, which subsequently responded to the overexpressed matrix metalloproteinase-9 (MMP-9) in diabetic lesions, leading to the responsive release of GOx. The released enzyme catalyzed glucose into gluconic acid and hydrogen peroxide (H_(2)O_(2)), which not only reduced glucose level within the diabetic wound, but also initiated the cascade reaction between H_(2)O_(2) with the Arg that was released from NPs, thereby achieving continuous production of NO for 7 days. Our findings demonstrate that a single administration of the MN patch could effectively heal non-infected or biofilm-infected diabetic wounds with the multifunctional properties.展开更多
Over the past decade,research has increasingly identified unique dysregulations in lipid metabolism within the tumor microenvironment(TME).Lipids,diverse biomolecules,not only constitute biological membranes but also ...Over the past decade,research has increasingly identified unique dysregulations in lipid metabolism within the tumor microenvironment(TME).Lipids,diverse biomolecules,not only constitute biological membranes but also function as signaling molecules and energy sources.Enhanced synthesis or uptake of lipids in the TME significantly promotes tumorigenesis and proliferation.Moreover,lipids secreted into the TME influence tumor-resident immune cells(TRICs),thereby aiding tumor survival against chemotherapy and immunotherapy.This review aims to highlight recent advancements in under-standing lipid metabolism in both tumor cells and TRICs,with a particular emphasis on exogenous lipid uptake and endogenous lipid de novo synthesis.Targeting lipid metabolism for intervention in anticancer therapies offers a promising therapeutic avenue for cancer treatment.Nano-drug delivery systems(NDDSs)have emerged as a means to maximize anti-tumor effects by rewiring tumor metabolism.This review provides a comprehensive overview of recent literature on the development of NDDSs targeting tumor lipid metabolism,particularly in the context of tumor immunotherapy.It covers four key aspects:reprogramming lipid uptake,reprogramming lipolysis,reshaping fatty acid oxidation(FAO),and reshuf-fing lipid composition on the cell membrane.The review concludes with a discussion of future prospects and challenges in this burgeoning field of research.展开更多
The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins.In recent years,toxins have been widely used as warheads for antibody-drug conjugates(ADCs)due to their eff-cient killing activity a...The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins.In recent years,toxins have been widely used as warheads for antibody-drug conjugates(ADCs)due to their eff-cient killing activity against various cancer cells.Although ADCs confer certain targeting properties to the toxins,low drug loading capacity,possible immunogenicity,and other drawbacks also limit the po-tential application of ADCs.Recently,non-ADC delivery strategies for toxins have been extensively investigated.To further understand the application of toxins in anti-tumor,this paper provided an over-view of prodrugs,nanodrug delivery systems,and biomimetic drug delivery systems.In addition,toxins and their combination strategies with other therapies were discussed.Finally,the prospect and challenge of toxins in cancertreatmentwerealso summarized.展开更多
Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability.Calcium-based materials can also deliver contrast agents,which can ...Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability.Calcium-based materials can also deliver contrast agents,which can enhance real-time imaging and exert a Ca^(2+)-interfering therapeutic effect.Based on these characteristics,amorphous calcium carbonate(ACC),as a brunch of calcium-based biomaterials,has the potential to become a widely used biomaterial.Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However,the standalone presence of ACC is unstable in vivo.Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination.ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo,such as Ca^(2+) with an immune-regulating ability and CO_(2) with an imaging-enhancing ability.Owing to these characteristics,ACC has been studied for selfsacrificing templates of carrier construction,targeted delivery of oncology drugs,immunomodulation,tumor imaging,tissue engineering,and calcium supplementation.Emphasis in this paper has been placed on the origin,structural features,and multiple applications of ACC.Meanwhile,ACC faces many challenges in clinical translation,and long-term basic research is required to overcome these challenges.We hope that this study will contribute to future innovative research on ACC.展开更多
Paclitaxel(PTX) is one of the most effective anticancer drugs for the treatment of various solid tumors, but its clinical use is limited by its poor solubility, low bioavailability, and severe systemic toxicity. Encap...Paclitaxel(PTX) is one of the most effective anticancer drugs for the treatment of various solid tumors, but its clinical use is limited by its poor solubility, low bioavailability, and severe systemic toxicity. Encapsulation of PTX in polymeric nanoparticles is used to overcome these problems but these micelles still need improvements in stability, pharmacokinetics, therapeutic efficacy, and safety profiles. In this study, we demonstrate a facile fabrication of a stable PTX-binding micelle made from poly(ethylene glycol)-block-dendritic polylysine, whose primary amines were reacted with phenethyl isothiocyanate(PEITC), a hydrophobic anticancer agent under clinical study. The amphiphilic conjugate(PEG-Gx-PEITC; Gx, the generation of the polylysine dendron) formed well-defined micelles whose core was composed of phenyl groups and thiourea groups binding PTX via π-π stacking and hydrogen bonding. Compared with the PTX-loaded poly(ethylene glycol)-block-poly(D,L-lactide)(PEGPDLLA/PTX) micelles in clinical use, PTX-loaded PEG-Gx-PEITC third-generation(PEG-G3-PEITC/PTX) micelles showed slowed blood clearance, enhanced tumor accumulation, and thus much improved in vivo therapeutic efficacy in both subcutaneous and orthotopic human breast cancer xenografts. Therefore, PEG-G3-PEITC is a promising drug delivery system for PTX in the treatment of breast cancer.展开更多
Nano-drug delivery strategies have been highlighted in cancer treatment, and much effort has been made in the optimization of bioavailability, biocompatibility, pharmacokinetics profiles, and in vivo distributions of ...Nano-drug delivery strategies have been highlighted in cancer treatment, and much effort has been made in the optimization of bioavailability, biocompatibility, pharmacokinetics profiles, and in vivo distributions of anticancer nano-drug delivery systems. However, problems still exist in the delicate balance between improved anticancer efficacy and reduced toxicity to normal tissues, and opportunities arise along with the development of smart stimuli-responsive delivery strategies. By on-demand responsiveness towards exogenous or endogenous stimulus, these smart delivery systems hold promise for advanced tumor-specificity as well as controllable release behavior in a spatial-temporal manner. Meanwhile, the blossom of nanotechnology, material sciences, and biomedical sciences has shed light on the diverse modern drug delivery systems with smart characteristics, versatile functions, and modification possibilities. This review summarizes the current progress in various strategies for smart drug delivery systems against malignancies and introduces the representative endogenous and exogenous stimuli-responsive smart delivery systems. It may provide references for researchers in the fields of drug delivery, biomaterials, and nanotechnology.展开更多
Delayed wound healing in diabetes is a global challenge,and the development of related drugs is a clinical problem to be solved.In this study,purpurolide C(PC),a small-molecule secondary metabolite of the endophytic f...Delayed wound healing in diabetes is a global challenge,and the development of related drugs is a clinical problem to be solved.In this study,purpurolide C(PC),a small-molecule secondary metabolite of the endophytic fungus Penicillium purpurogenum,was found to promote diabetic wound healing.To investigate the key regulation targets of PC,in vitro RNA-seq,molecular docking calcula-tions,TLR4-MD2 dimerization SDS-PAGE detection,and surface plasmon resonance(SPR)were per-formed,indicating that PC inhibited inflammatory macrophage activation by inhibiting both TLR4-MD2 dimerization and MYD88 phosphorylation.Tlr4 knockout in vivo attenuated the promotion effect of PC on wound healing.Furthermore,a delivery system consisting of macrophage liposome and GelMA-based microneedle patches combined with PC(PC@MLIP MN)was developed,which overcame the poor water solubility and weak skin permeability of PC,so that successfully punctured the skin and delivered PC to local tissues,and accurately regulated macrophage polarization in diabetic wound management.Overall,PC is an anti-inflammatory small molecule compound with a well-defined structure and dualtarget regulation,and the PC@MLIP MN is a promising novel biomaterial for the management of diabetic wound.展开更多
Extracellular vesicles(EVs)are phospholipid bilayer vesicles actively secreted by cells,that contain a variety of functional nucleic acids,proteins,and lipids,and are important mediums of intercellular communication.B...Extracellular vesicles(EVs)are phospholipid bilayer vesicles actively secreted by cells,that contain a variety of functional nucleic acids,proteins,and lipids,and are important mediums of intercellular communication.Based on their natural properties,EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers.Among them,plant-derived nanovesicles(PNVs)are characterized as natural disease therapeutics with many advantages such as simplicity,safety,eco-friendliness,low cost,and low toxicity due to their abundant resources,large yield,and low risk of immunogenicity in vivo.This review systematically introduces the biogenesis,isolation methods,physical characterization,and components of PNVs,and describes their administration and cellular uptake as therapeutic agents.We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers,including anti-inflammatory,anticancer,wound healing,regeneration,and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19.Finally,the toxicity and immunogenicity,the current clinical application,and the possible challenges in the future development of PNVs were analyzed.We expect the functions of PNVs to be further explored to promote clinical translation,thereby facilitating the development of a new framework for the treatment of human diseases.展开更多
Inspired by the adaptation of cells to the surrounding environment,the combination of cell membrane and nanomaterials has gradually become a new type of biomimetic nanocomposite.The construction of endogenous membrane...Inspired by the adaptation of cells to the surrounding environment,the combination of cell membrane and nanomaterials has gradually become a new type of biomimetic nanocomposite.The construction of endogenous membrane biomimetic nanocarriers(EMBNs)not only retains the structure of membrane surface protein,but also has the properties of nanoparticles(NPs),also provides the ability of natural interaction between nanomaterials and organisms,thus overcoming the severe challenges faced by traditional nanodelivery systems in clinical application.In this paper,the construction methods of EMBNs are reviewed,focusing on a simple method to prepare membrane proteins.Secondly,EMBNs were classified according a variety of cell membranes.Finally,the unique advantages of EMBNs in nanomedicine are introduced,including improving biocompatibility,homologous targeting ability,prolonging blood circulation time and immune escape abilty.In nanomedicine,such as targeted delivery,phototherapy,immunotherapy and tumor imaging,multifaceted biological interfaces through membrane masking provide a new approach for the development of multifunctional NPs.展开更多
In recent years,magnetic nanoparticles(MNPs)have received great attention within the field of biomedicine,especially for cancer therapy.This is because MNPs have many excellent physical and chemical properties to prov...In recent years,magnetic nanoparticles(MNPs)have received great attention within the field of biomedicine,especially for cancer therapy.This is because MNPs have many excellent physical and chemical properties to provide sufficient imaging information along with satisfactory therapeutic efficacy.Moreover,by virtue of various modification strategies,the obtained multifunctional MNPs can further achieve synergized multimodal cancer theranostic,which is worthy of further study.In this review,we summarize the recent developments in imaging-guided strategies and synergistic cancer therapy based on multifunctional MNPs.Then,we discuss the challenge and perspective of the next generation of MNPs-based imaging-guided cancer therapy,hoping to provide guidance in potential applications.展开更多
There has been unprecedented progress in the development of biomedical nanotechnology and nanoma- terials over the past few decades, and nanoparticle-based drug delivery systems （DDSs） have great potential for clin-...There has been unprecedented progress in the development of biomedical nanotechnology and nanoma- terials over the past few decades, and nanoparticle-based drug delivery systems （DDSs） have great potential for clin- ical applications. Among these, magnetic drug delivery systems （MDDSs） based on magnetic nanoparticles （MNPs） are attracting increasing attention owing to their favor- able biocompatibility and excellent multifunctional loading capability. MDDSs primarily have a solid core of super paramagnetic maghemite （y-Fe^03） or magnetite （Fe304） nanoparticles ranging in size from 10 to 100nm. Their surface can be functionalized by organic and/or inorganic modification. Further conjugation with targeting ligands, drug loading, and MNP assembly can provide complex magnetic delivery systems with improved targeting efficacy and reduced toxicity. Owing to their sensitive response to external magnetic fields, MNPs and their assemblies have been developed as novel smart delivery systems. In this review, we first summarize the basic physicochemical and magnetic properties of desirable MDDSs that fulfill the requirements for specific clinical applications. Secondly, we discuss the surface modifications and functionalization issues that arise when designing elaborate MDDSs for future clinical uses. Finally, we highlight recent progress in the design and fabrication of MNPs, magnetic assemblies, and magnetic microbnbbles and liposomes as MDDSs for cancer diagnosis and therapy. Recently, researchers have focused on enhanced targeting efficacy and theranostics by applying step-by-step sequential treatment, and by magnetically mod- ulating dosing regimens, which are the current challenges for clinical applications.展开更多
In the present study, β-cyclodextrin-grafted chitosan nanoparticles （β-CD- g-CS NPs） were prepared using a new ionic gelation strategy involving a synergistic effect of NaCI （150 mmol/L）, 4-（2-hydroxyethyl）-1-...In the present study, β-cyclodextrin-grafted chitosan nanoparticles （β-CD- g-CS NPs） were prepared using a new ionic gelation strategy involving a synergistic effect of NaCI （150 mmol/L）, 4-（2-hydroxyethyl）-1-piperazineethanesulfonic acid （HEPES, 10 mmol/L）, and water bath sonication. This new strategy afforded smaller and more monodisperse β-CD-g-CS NPs vs. the classical ionic gelation method. New HA8β-CD-g-CS NPs were also prepared using the above-mentioned strategy by adding hyaluronic acid （HA） to the β-CD-g-CS copolymer at different weight ratios until the ZP values conversion. The best result was obtained with the weight ratio of w（HA）：w（β-CD-g-CS） = 2：1 and furnished new spherical and smooth HA/β-CD-g-CS NPs. Furthermore, the stability of β- CD-g-CS NPs and HA/β-CD-g-CS NPs at 4℃ in physiological medium （pH 7.4） was compared for 3 weeks period and showed that HA/β-CD-g-CS NPs were more stable all maintaining their monodispersity and high negative ZP values compared to β-CD-g-CS NPs. Finally, preliminary study of HA/β-CD-g-CS NPs as carrier for the controlled release of the anticancer drug doxorubicin was investigated. These new HA/β-CD-g-CS NPs can potentially be used as drug delivery and targeting systems for cancer treatment.展开更多
文摘Diabetic macular edema(DME)is a very important and well-known cause of visual loss in diabetics.Blood-retina barrier disruption and consequent intraretinal fluid accumulation may lead to retinal thickening at the posterior pole namely DME.Even though it is not clearly understood,current evidence suggests that chronic low-grade inflammation characterized with various cytokines has a major role in the occurrence of DME.Clinical trials are continuously shaping our treatment approaches for the eyes with DME.Today,vascular endothelial growth factor(VEGF)inhibitor and steroid administrations are the main alternatives in DME treatment.Dexamethasone(DEX)implant(Ozurdex®;Allergan,Inc.,Irvine,CA,United States)was approved by the United States Food&Drug Administration in 2014 for DME treatment.The implant is made up of a biodegradable solid copolymer that is broken down by releasing its active ingredient into the vitreous cavity over time.Biphasic release feature of this sustained-release drug delivery system ensures its efficacy for up to 6 mo with an acceptable and manageable safety profile.DEX implant provides a favorable anatomical and functional outcome in DME as shown in several randomized-controlled studies but has a relatively higher ocular side-effect profile such as increased risk of cataract formation and raised intraocular pressure when compared to the gold standard anti-VEGF agents.Thus,DEX implant becomes the second-line treatment option demonstrating inadequate clinical response to anti-VEGF therapy.However,it can be preferred as the first-line treatment in vitrectomized and pseudophakic eyes.Even in some selected conditions DEX implant is favored over anti-VEGF agents where the use of VEGF-inhibitors is either inappropriate or contraindicated such as the patients with a recent history of a major cardiovascular or cerebrovascular event,pregnancy and noncompliant to frequent visits.This mini-review briefly overviews the efficacy,safety profile and complications of DEX implant and summarizes the outcome of DEX implant administration in major clinical studies on DME treatment.
基金supported by the National Natural Science Foundation of China(No.82274104,82074024,82374042,82104688,China)National Ten Thousand Talents Program for Young Top-notch Talents,the Natural Science Foundation of Jiangsu Province(No.BK20240144,China)+2 种基金Jiangsu 333 High level Talent Training Project,the Innovation Projects of State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture(No.NZYSKL240103,China)Nanjing University of Chinese Medicine’s Project(No.RC202407,China)supported by the College Students’Innovative Entrepreneurial Training(No.202210315056Y,202310315055Z,China).
文摘Extracellular vesicles(EVs)are crucial for facilitating intercellular communication,promoting cell migration,and orchestrating the immune response.Recently,EVs can diagnose and treat tumors.EVs can be measured as biomarkers to provide information about the type of disease and therapeutic efficacy.Furthermore,EVs with lower immunogenicity and better biocompatibility are natural carriers of chemicals and gene drugs.Herein,we review the molecular composition,biogenesis,and separation methods of EVs.We also highlight the important role of EVs from different origins as biomarkers and drug delivery systems in tumor therapy.Finally,we provide deep insights into how EVs play a role in reversing the immunosuppressive microenvironment.
基金Shanghai Xuhui medical research project(SHXH202110 and SHXH202230,China)Natural Science Foundation of Shanghai(21ZR1447900,China)Key Discipline Construction Project(SHXHZDXK202310,China)of Shanghai Xuhui Health System.
文摘Intravesical drug delivery(IDD),as a noninvasive,local pathway of administration,has great clinical significance for bladder diseases,especially bladder cancer.Despite the many advantages of IDD such as enhanced focal drug exposure and avoidance of systemic adverse drug reactions,the effectiveness of drug delivery is greatly challenged by the physiological barriers of the bladder.In this review,the routes and barriers encountered in IDD are first discussed,and attention is paid to the potential internal/mucosal retention and absorption-transport mechanisms of drugs.On this basis,the avoidance,overcoming and utilization of the"three barriers"is further emphasized,and current design and fabrication strategies for intravesical drug delivery systems(IDDSs)are described mainly from the perspectives of constructing drug reservoirs,enhancing permeability and targeting,with the hope of providing systematic understanding and inspirations for the research of novel IDDSs and their treatment of bladder diseases.
基金National Natural Science Foundation of China(NSFC,Nos.82373798,52103182)the Special Project for Significant New Drug Research and Development in the Major National Science and Technology Projects of China(project No.2020ZX09201007)Innovation Transformation Research Project of Zhongnan Hospital of Wuhan University(project No.YXCXZH2024003,China).
文摘High glucose level, bacterial infection, and persistent inflammation within the microenvironment are key factors contributing to the delay of diabetic ulcers healing, while traditional therapeutic methods generally fail to address these issues simultaneously. Here, we present a spatiotemporally responsive cascade bilayer microneedle (MN) patch for accelerating diabetic wound healing via local glucose depletion and sustained nitric oxide (NO) release for long-term antibacterial and anti-inflammatory effects. The MN patch (G/AZ-MNs) possesses a degradable tip layer loading glucose oxidase (GOx), as well as a dissolvable base layer encapsulating l-arginine (Arg)-loaded nanoparticles (NPs). After wound administration, the base part rapidly dissolved, resulting in prompt separation of the MN tip within the wound tissue, which subsequently responded to the overexpressed matrix metalloproteinase-9 (MMP-9) in diabetic lesions, leading to the responsive release of GOx. The released enzyme catalyzed glucose into gluconic acid and hydrogen peroxide (H_(2)O_(2)), which not only reduced glucose level within the diabetic wound, but also initiated the cascade reaction between H_(2)O_(2) with the Arg that was released from NPs, thereby achieving continuous production of NO for 7 days. Our findings demonstrate that a single administration of the MN patch could effectively heal non-infected or biofilm-infected diabetic wounds with the multifunctional properties.
基金National Natural Science Foundation of China(82174095,China)Natural Science Foundation of Zhejiang Province(LZ22H290001,China)Zhejiang Province Traditional Chinese Medicine Science and Technology Project(2023ZL362,China).
文摘Over the past decade,research has increasingly identified unique dysregulations in lipid metabolism within the tumor microenvironment(TME).Lipids,diverse biomolecules,not only constitute biological membranes but also function as signaling molecules and energy sources.Enhanced synthesis or uptake of lipids in the TME significantly promotes tumorigenesis and proliferation.Moreover,lipids secreted into the TME influence tumor-resident immune cells(TRICs),thereby aiding tumor survival against chemotherapy and immunotherapy.This review aims to highlight recent advancements in under-standing lipid metabolism in both tumor cells and TRICs,with a particular emphasis on exogenous lipid uptake and endogenous lipid de novo synthesis.Targeting lipid metabolism for intervention in anticancer therapies offers a promising therapeutic avenue for cancer treatment.Nano-drug delivery systems(NDDSs)have emerged as a means to maximize anti-tumor effects by rewiring tumor metabolism.This review provides a comprehensive overview of recent literature on the development of NDDSs targeting tumor lipid metabolism,particularly in the context of tumor immunotherapy.It covers four key aspects:reprogramming lipid uptake,reprogramming lipolysis,reshaping fatty acid oxidation(FAO),and reshuf-fing lipid composition on the cell membrane.The review concludes with a discussion of future prospects and challenges in this burgeoning field of research.
基金This work was supported by the National Postdoctoral Foundation of China(No.2023M730375)Liaoning Province Department of Education Project(No.LJKMZ20221365,China)+3 种基金the State Key Laboratory of Natural and Biomimetic Drugs(No.K202215,China)the National Natural Science Foundation of China(No.82173766)Liaoning Province Applied Basic Research Program(No.2022JH2/101300097,China)the Natural Science Foundation of Shandong Province(No.ZR2021QH084,China)。
文摘The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins.In recent years,toxins have been widely used as warheads for antibody-drug conjugates(ADCs)due to their eff-cient killing activity against various cancer cells.Although ADCs confer certain targeting properties to the toxins,low drug loading capacity,possible immunogenicity,and other drawbacks also limit the po-tential application of ADCs.Recently,non-ADC delivery strategies for toxins have been extensively investigated.To further understand the application of toxins in anti-tumor,this paper provided an over-view of prodrugs,nanodrug delivery systems,and biomimetic drug delivery systems.In addition,toxins and their combination strategies with other therapies were discussed.Finally,the prospect and challenge of toxins in cancertreatmentwerealso summarized.
基金supported by Beijing Nova Program(Z211100002121127 and 20220484219,China)Beijing Natural Science Foundation(L212059,China)+1 种基金Fundamental Research Funds for the Central Universities(3332021101,China)CAMS Innovation Fund for Medical Sciences(CIFMS,2021-I2M-1-026 and 2021-I2M-1-028,China).
文摘Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and biodegradability.Calcium-based materials can also deliver contrast agents,which can enhance real-time imaging and exert a Ca^(2+)-interfering therapeutic effect.Based on these characteristics,amorphous calcium carbonate(ACC),as a brunch of calcium-based biomaterials,has the potential to become a widely used biomaterial.Highly functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However,the standalone presence of ACC is unstable in vivo.Additives are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its destination.ACC has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo,such as Ca^(2+) with an immune-regulating ability and CO_(2) with an imaging-enhancing ability.Owing to these characteristics,ACC has been studied for selfsacrificing templates of carrier construction,targeted delivery of oncology drugs,immunomodulation,tumor imaging,tissue engineering,and calcium supplementation.Emphasis in this paper has been placed on the origin,structural features,and multiple applications of ACC.Meanwhile,ACC faces many challenges in clinical translation,and long-term basic research is required to overcome these challenges.We hope that this study will contribute to future innovative research on ACC.
基金supported by the National Natural Science Foundation of China (U1501243, 51603181)the National Basic Research Program (2014CB931900)+1 种基金the National Natural Science Foundation of China (51603181)the Fundamental Research Funds for the Central Universities (2016QNA4024) for financial support
文摘Paclitaxel(PTX) is one of the most effective anticancer drugs for the treatment of various solid tumors, but its clinical use is limited by its poor solubility, low bioavailability, and severe systemic toxicity. Encapsulation of PTX in polymeric nanoparticles is used to overcome these problems but these micelles still need improvements in stability, pharmacokinetics, therapeutic efficacy, and safety profiles. In this study, we demonstrate a facile fabrication of a stable PTX-binding micelle made from poly(ethylene glycol)-block-dendritic polylysine, whose primary amines were reacted with phenethyl isothiocyanate(PEITC), a hydrophobic anticancer agent under clinical study. The amphiphilic conjugate(PEG-Gx-PEITC; Gx, the generation of the polylysine dendron) formed well-defined micelles whose core was composed of phenyl groups and thiourea groups binding PTX via π-π stacking and hydrogen bonding. Compared with the PTX-loaded poly(ethylene glycol)-block-poly(D,L-lactide)(PEGPDLLA/PTX) micelles in clinical use, PTX-loaded PEG-Gx-PEITC third-generation(PEG-G3-PEITC/PTX) micelles showed slowed blood clearance, enhanced tumor accumulation, and thus much improved in vivo therapeutic efficacy in both subcutaneous and orthotopic human breast cancer xenografts. Therefore, PEG-G3-PEITC is a promising drug delivery system for PTX in the treatment of breast cancer.
基金supported by the projects of National Natural Science Foundation of China(No.81973259,82073789,81803472)the project for Innovative Research Group at Higher Educational Institutions in Chongqing(CXQT20006,China).
文摘Nano-drug delivery strategies have been highlighted in cancer treatment, and much effort has been made in the optimization of bioavailability, biocompatibility, pharmacokinetics profiles, and in vivo distributions of anticancer nano-drug delivery systems. However, problems still exist in the delicate balance between improved anticancer efficacy and reduced toxicity to normal tissues, and opportunities arise along with the development of smart stimuli-responsive delivery strategies. By on-demand responsiveness towards exogenous or endogenous stimulus, these smart delivery systems hold promise for advanced tumor-specificity as well as controllable release behavior in a spatial-temporal manner. Meanwhile, the blossom of nanotechnology, material sciences, and biomedical sciences has shed light on the diverse modern drug delivery systems with smart characteristics, versatile functions, and modification possibilities. This review summarizes the current progress in various strategies for smart drug delivery systems against malignancies and introduces the representative endogenous and exogenous stimuli-responsive smart delivery systems. It may provide references for researchers in the fields of drug delivery, biomaterials, and nanotechnology.
基金supported by grants from National Key R&D Program of China(Grant NO.2022YFC2504200 to Yi Liu)the National Nature Science Foundation of China(81991504 and 81974149 to Yi Liu,82073978 to Sheng Lin,82201053 to Yitong Liu,81803397 to Guiyang Xia,82122015 to Junji Xu)+6 种基金the Innovation Research Team Project of Beijing Stomatological Hospital,Capital Medical University(CXTD202202 to Yi Liu,China)the Innovation Foundation of Beijing Stomatological Hospital,Capital Medical University(21-09-18 to Lijia Guo,China)the Beijing Stomatological Hospital,Capital Medical University Young Scientist Program(YSP202105 to Yitong Liu,China)the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(ZYLX202121 to Yi Liu,China)Beijing Municipal Administration of Hospitals'Ascent Plan(DFL20181501 to Yi Liu,China)Beijing Municipal Administration of Hospitals'Youth Programme(QML20181501 to Lijia Guo,QML20231506 to Yitong Liu,China)Beijing Municipal Administration of Hospitals Incubating Program(PX2023054 to Lijia Guo,China).
文摘Delayed wound healing in diabetes is a global challenge,and the development of related drugs is a clinical problem to be solved.In this study,purpurolide C(PC),a small-molecule secondary metabolite of the endophytic fungus Penicillium purpurogenum,was found to promote diabetic wound healing.To investigate the key regulation targets of PC,in vitro RNA-seq,molecular docking calcula-tions,TLR4-MD2 dimerization SDS-PAGE detection,and surface plasmon resonance(SPR)were per-formed,indicating that PC inhibited inflammatory macrophage activation by inhibiting both TLR4-MD2 dimerization and MYD88 phosphorylation.Tlr4 knockout in vivo attenuated the promotion effect of PC on wound healing.Furthermore,a delivery system consisting of macrophage liposome and GelMA-based microneedle patches combined with PC(PC@MLIP MN)was developed,which overcame the poor water solubility and weak skin permeability of PC,so that successfully punctured the skin and delivered PC to local tissues,and accurately regulated macrophage polarization in diabetic wound management.Overall,PC is an anti-inflammatory small molecule compound with a well-defined structure and dualtarget regulation,and the PC@MLIP MN is a promising novel biomaterial for the management of diabetic wound.
基金supported by National Natural Science Foundation of China(82274103,82074272,China)Program of Shanghai Academic Research Leader(21XD1403400,China)+1 种基金the Science and Technology Commission of Shanghai Municipality(20S21900300,China)Shanghai Sailing Program(20YF1412100,China)。
文摘Extracellular vesicles(EVs)are phospholipid bilayer vesicles actively secreted by cells,that contain a variety of functional nucleic acids,proteins,and lipids,and are important mediums of intercellular communication.Based on their natural properties,EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers.Among them,plant-derived nanovesicles(PNVs)are characterized as natural disease therapeutics with many advantages such as simplicity,safety,eco-friendliness,low cost,and low toxicity due to their abundant resources,large yield,and low risk of immunogenicity in vivo.This review systematically introduces the biogenesis,isolation methods,physical characterization,and components of PNVs,and describes their administration and cellular uptake as therapeutic agents.We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers,including anti-inflammatory,anticancer,wound healing,regeneration,and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19.Finally,the toxicity and immunogenicity,the current clinical application,and the possible challenges in the future development of PNVs were analyzed.We expect the functions of PNVs to be further explored to promote clinical translation,thereby facilitating the development of a new framework for the treatment of human diseases.
基金This work was supported by the Development Plan of Youth Innovation Team in Colleges and Universities of Shandong Province(2020KJC003).
文摘Inspired by the adaptation of cells to the surrounding environment,the combination of cell membrane and nanomaterials has gradually become a new type of biomimetic nanocomposite.The construction of endogenous membrane biomimetic nanocarriers(EMBNs)not only retains the structure of membrane surface protein,but also has the properties of nanoparticles(NPs),also provides the ability of natural interaction between nanomaterials and organisms,thus overcoming the severe challenges faced by traditional nanodelivery systems in clinical application.In this paper,the construction methods of EMBNs are reviewed,focusing on a simple method to prepare membrane proteins.Secondly,EMBNs were classified according a variety of cell membranes.Finally,the unique advantages of EMBNs in nanomedicine are introduced,including improving biocompatibility,homologous targeting ability,prolonging blood circulation time and immune escape abilty.In nanomedicine,such as targeted delivery,phototherapy,immunotherapy and tumor imaging,multifaceted biological interfaces through membrane masking provide a new approach for the development of multifunctional NPs.
基金support from the National Natural Science Foundation of China(52201198,52027801,and 51631001)the National Key R&D Program of China(2017YFA0206301)the China-Germany Collaboration Project(M-0199).
文摘In recent years,magnetic nanoparticles(MNPs)have received great attention within the field of biomedicine,especially for cancer therapy.This is because MNPs have many excellent physical and chemical properties to provide sufficient imaging information along with satisfactory therapeutic efficacy.Moreover,by virtue of various modification strategies,the obtained multifunctional MNPs can further achieve synergized multimodal cancer theranostic,which is worthy of further study.In this review,we summarize the recent developments in imaging-guided strategies and synergistic cancer therapy based on multifunctional MNPs.Then,we discuss the challenge and perspective of the next generation of MNPs-based imaging-guided cancer therapy,hoping to provide guidance in potential applications.
基金financially funded by the National Natural Science Foundation of China (NSFC, 31370019, 61420106012)the project of National Key Basic Research Program of China (2013CB733804)+1 种基金The funding partially comes from the Fundamental Research Funds for the Central Universities (2242016K41072)Zhong Ying Young Scholar of Southeast University as well as the support fromthe Collaborative Innovation Center of Suzhou Nano Science and Technology
文摘There has been unprecedented progress in the development of biomedical nanotechnology and nanoma- terials over the past few decades, and nanoparticle-based drug delivery systems （DDSs） have great potential for clin- ical applications. Among these, magnetic drug delivery systems （MDDSs） based on magnetic nanoparticles （MNPs） are attracting increasing attention owing to their favor- able biocompatibility and excellent multifunctional loading capability. MDDSs primarily have a solid core of super paramagnetic maghemite （y-Fe^03） or magnetite （Fe304） nanoparticles ranging in size from 10 to 100nm. Their surface can be functionalized by organic and/or inorganic modification. Further conjugation with targeting ligands, drug loading, and MNP assembly can provide complex magnetic delivery systems with improved targeting efficacy and reduced toxicity. Owing to their sensitive response to external magnetic fields, MNPs and their assemblies have been developed as novel smart delivery systems. In this review, we first summarize the basic physicochemical and magnetic properties of desirable MDDSs that fulfill the requirements for specific clinical applications. Secondly, we discuss the surface modifications and functionalization issues that arise when designing elaborate MDDSs for future clinical uses. Finally, we highlight recent progress in the design and fabrication of MNPs, magnetic assemblies, and magnetic microbnbbles and liposomes as MDDSs for cancer diagnosis and therapy. Recently, researchers have focused on enhanced targeting efficacy and theranostics by applying step-by-step sequential treatment, and by magnetically mod- ulating dosing regimens, which are the current challenges for clinical applications.
文摘In the present study, β-cyclodextrin-grafted chitosan nanoparticles （β-CD- g-CS NPs） were prepared using a new ionic gelation strategy involving a synergistic effect of NaCI （150 mmol/L）, 4-（2-hydroxyethyl）-1-piperazineethanesulfonic acid （HEPES, 10 mmol/L）, and water bath sonication. This new strategy afforded smaller and more monodisperse β-CD-g-CS NPs vs. the classical ionic gelation method. New HA8β-CD-g-CS NPs were also prepared using the above-mentioned strategy by adding hyaluronic acid （HA） to the β-CD-g-CS copolymer at different weight ratios until the ZP values conversion. The best result was obtained with the weight ratio of w（HA）：w（β-CD-g-CS） = 2：1 and furnished new spherical and smooth HA/β-CD-g-CS NPs. Furthermore, the stability of β- CD-g-CS NPs and HA/β-CD-g-CS NPs at 4℃ in physiological medium （pH 7.4） was compared for 3 weeks period and showed that HA/β-CD-g-CS NPs were more stable all maintaining their monodispersity and high negative ZP values compared to β-CD-g-CS NPs. Finally, preliminary study of HA/β-CD-g-CS NPs as carrier for the controlled release of the anticancer drug doxorubicin was investigated. These new HA/β-CD-g-CS NPs can potentially be used as drug delivery and targeting systems for cancer treatment.
