Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory sym...Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory symptoms,including bronchiolitis and pneumonia.Baicalin(BA)exhibits significant therapeutic effects against RSV infection through mechanisms of viral inhibition and anti-inflammatory action.Nonetheless,the clinical application of BA is constrained by its low solubility and bioavailability.In this study,we prepared BA nanodrugs(BA NDs)with enhanced water solubility utilizing the supramolecular self-assembled strategy,and we further conducted a comparative analysis of this pharmacological activity between free drugs and NDs of BA.Both in vitro and in vivo results demonstrated that BA NDs significantly enhanced the dual effects of viral inhibition and inflammation relief compared to free BA,attributed to prolonged lung retention,improved cellular uptake,and increased targeting affinity.Our study confirms that the nanosizing strategy,a straightforward approach to enhance drug solubility,can also increase biological activity compared to free drugs with the same content,thereby providing a potential ND for RSV treatment.This correlation analysis between the existing forms of drugs and their biological activity offers a novel perspective for research on the active ingredients of traditional Chinese medicine.展开更多
Rheumatoid arthritis(RA)is a sophisticated autoimmune disorder involving in the pathological characteristics of joint inflammation,synovial hyperplasia,pannus formation,cartilage destruction and bone erosion.Current r...Rheumatoid arthritis(RA)is a sophisticated autoimmune disorder involving in the pathological characteristics of joint inflammation,synovial hyperplasia,pannus formation,cartilage destruction and bone erosion.Current rheumatic therapy drugs such as non-steroidal anti-inflammatory drugs,glucocorticoids,disease-modifying antirheumatic drugs,or biologics are remarkably restricted by their poor blood circulation capability,unsatisfied drug loading efficiency,off-target irritation,and carrier-related toxicity.Recently,great efforts have concentrated on carrier-free nanoparticulated delivery strategy,and multifarious carrier-free nanodrugs including nanocrystal,nanoparticle,and nanomicelle have been manifested to possess boosted stability,extended circulation capability,enhanced drug accumulation at the inflammatory joint,and high-efficiency and low-toxicity therapeutic outcomes in RA models.Hence,this review provides a comprehensive summary of carrier-free nanodrugs for efficient RA treatment,with an emphasis on nanocrystal,nanoparticle,and nanomicelle,and then the ongoing challenges and prospects of carrier-free nanodrugs are discussed.展开更多
Numerous reports have demonstrated the construction of supramolecular nanodrugs(SNDs)via theπ-πstacking of drug molecules for antitumor applications because most drugs possess aromatic rings or other planar conjugat...Numerous reports have demonstrated the construction of supramolecular nanodrugs(SNDs)via theπ-πstacking of drug molecules for antitumor applications because most drugs possess aromatic rings or other planar conjugate units.However,the destruction ofπ-πstacking and the subsequent disassembly of SNDs under tumor microenvironment(TME),which is the precondition for drug release,have not been clearly described.In this work,based on a disassembly model ofπ-πstacked naphthoquinone SNDs,the influence of co-assembled drugs on disassembly is delineated.Both the experimental observation and computational simulation indicate that the disassembly of SNDs under simulated TME highly depends on the disassembly activation energy(ΔE_(dis))of neighboringπ-πstacked molecules.Owing to the highΔE_(dis),the disassembly of self-assembled naphthoquinone SNDs is greatly restricted.Meaningfully,theΔE_(dis)is the sum of a series of activation energy according to the specific stimuli of TME.Thus,a concept of stimuli-responsive drug-mates is proposed for boosting the disassembly ofπ-πstacked SNDs,namely the foremost co-assembly ofπ-conjugated drugs with additional drug molecules that possess relatively weakπ-πinteraction but high TME responsiveness.Further computational simulation reveals that the introduction of stimuli-responsive drug-mates significantly lowers theΔE_(dis),thus accelerating the disassembly of SNDs and the release of drug payloads.Holding the advantages ofπ-conjugated drug library,the concept of stimuli-responsive drug-mates gives an extensive design ofπ-πstacked SNDs toward heterogeneous nidus microenvironment responsiveness,which highlights the superiority of widely used drug co-assembly strategy in constructing multifunctional SNDs.展开更多
The considerable development of carrier-free nanodrugs has been achieved due to their high drug-loading capability,simple preparation method,and offering“all-in-one”functional platform features.However,the native de...The considerable development of carrier-free nanodrugs has been achieved due to their high drug-loading capability,simple preparation method,and offering“all-in-one”functional platform features.However,the native defects of carrier-free nanodrugs limit their delivery and release behavior throughout the in vivo journey,which significantly compromise the therapeutic efficacy and hinder their further development in cancer treatment.In this review,we summarized and discussed the recent strategies to enhance drug delivery and release of carrier-free nanodrugs for improved cancer therapy,including optimizing the intrinsic physicochemical properties and external modification.Finally,the corresponding challenges that carrier-free nanodrugs faced are discussed and the future perspectives for its application are presented.We hope this review will provide constructive information for the rational design of more effective carrier-free nanodrugs to advance therapeutic treatment.展开更多
Nanodrugs capable of aggregating in the tumor microenvironment(TME)have demonstrated great efficiency in improving the therapeutic outcome.Among vari-ous approaches,the strategy utilizing electrostatic interaction as ...Nanodrugs capable of aggregating in the tumor microenvironment(TME)have demonstrated great efficiency in improving the therapeutic outcome.Among vari-ous approaches,the strategy utilizing electrostatic interaction as a driving force to achieve intratumor aggregation of nanodrugs has attracted great attention.However,the great difference between the two nanodrugs with varied physicochemical prop-erties makes their synchronous transport in blood circulation and equal-opportunity tumor uptake impossible,which significantly detracts from the beneficial effects of nanodrug aggregation inside tumors.We herein propose a new strategy to construct a pair of extremely similar nanodrugs,referred to as“twins-like nanodrugs(TLNs)”,which have identical physicochemical properties including the same morphology,size,and electroneutrality to render them the same blood circulation time and tumor entrance.The 1:1 mixture of TLNs(TLNs-Mix)intravenously injected into a mouse model efficiently accumulates in tumor sites and then transfers to oppositely charged nanodrugs for electrostatic interaction-driven coalescence via responding to matrix metalloproteinase-2(MMP-2)enriched in tumor.In addition to enhanced tumor retention,the thus-formed micron-sized aggregates show high echo intensity essen-tial for ultrasound imaging as well as ultrasound-triggered penetrative drug delivery.Owing to their distinctive features,the TLNs-Mix carrying sonosensitizer,immune adjuvant,and ultrasound contrast agent exert potent sonodynamic immunotherapy against hypovascular hepatoma,demonstrating their great potential in treating solid malignancies.展开更多
A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynami...A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynamic therapy(PDT).The obtained nanomicelle possessed a spherical structure with a diameter of(18.0±2.2)nm and a zeta potential of approximately -18 mV.Besides,the nanomicelle exhibited excellent photostability,biocompatibility,and phototoxicity,and could effectively reach the tumor region via the enhanced permeability and retention effect.Additionally,it could be found that the TPGS/Ppa nanomicelle exhibited higher phototoxicity against 4T1 murine mammary cancer cells than free Ppa.In the 4T1 tumor-bearing mouse model,the nanomicelle showed an excellent antitumor therapeutic effect.This study develops a new type of photodynamic nanomicelle TPGS/Ppa,which can increase the accumulation of drugs and prolong their tumor retention time,providing a feasible strategy for realizing the delivery of small-molecule hydrophobic drugs and tumor PDT.展开更多
Traditional Chinese medicines(TCMs)have been used for centuries to treat and manage various diseases.However,their effective delivery to targeted sites may be a major challenge due to their poor water solubility,low b...Traditional Chinese medicines(TCMs)have been used for centuries to treat and manage various diseases.However,their effective delivery to targeted sites may be a major challenge due to their poor water solubility,low bio-availability,and potential toxicity.Nanocarriers,such as liposomes,polymeric nanoparticles,inorganic nanoparticles,and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations.This article summarizes the recent progress in nanocarrier-based delivery systems.Nanotechnology can broaden the scope of applications of traditional Chinese medicine.The concept of nano-traditional Chinese medicine(nano-TCM)is introduced,and the progress of nanomedicine,the advantages,and the development direction of nano-TCM are reviewed,providing new ideas for the development of nano-TCM.展开更多
Although nanodrugs based on antiangiogenic and oxidative stress have received widespread attention in oncotherapy,low delivery efficiency and drug payload have greatly hindered their further applications.The self-targ...Although nanodrugs based on antiangiogenic and oxidative stress have received widespread attention in oncotherapy,low delivery efficiency and drug payload have greatly hindered their further applications.The self-targeting carrier-free metal-organic nanodrugs are constructed via the dynamic ligand-driven self-assembly of anti-angiogenesis pseudolaric acid B(PAB),Fenton-like agent copper ion,and the chemo-drug pemetrexed(PEM)to enhance anti-angiogenic-oxidative stress oncotherapy.After intravenous injection,it is found that such nanodrugs can be efficiently accumulated in tumor site and internalized into tumor cells by folate receptors-mediated self-targeting.After that,nanodrugs are disassembled to achieve the burst release of drugs under stimuli of acidic lysosome and endogenous glutathione(GSH).Interestingly,the released Cu[II]can efficiently decompose the endogenous hydrogen peroxide(H2O2)into hydroxyl radicals(·OH)and significantly weaken reactive oxygen species(ROS)elimination by downregulating endogenous GSH to self-amplify intracellular oxidative stress.Meanwhile,the released PAB can obviously inhibit the secretion of vascular endothelial growth factor(VEGF),block the formation of new blood vessels,and regulate the conformation of VEGF receptor 2(VEGFR2)to inhibit the angiogenesis signaling pathway.After two weeks of treatment,PEM-Cu[II]-PAB(PCP)nanodrugs achieved a 95%tumor inhibition rate and 100%survival rate in tumor-bearing mice.Taken together,our study can expect to provide a promising method for targeted oncotherapy based on the synergistic therapy of antiangiogenic or oxidative stress.展开更多
Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions.Herein,we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation ...Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions.Herein,we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation followed by circularly amplified ROS-triggered drug release via positive-feedback loop.The di-selenide-bridged prodrug synthesized from vitamin E succinate and methotrexate(MTX)self-assembles into nanoparticles(VSeM);decorating acidity-cleavable PEG onto VSeM surface temporarily shields the targeting ability of MTX to evade immune clearance and consequently elongate circulation time.Upon reaching tumor sites,acidity-triggered detachment of PEG results in targeting recovery to enhance tumor cell uptake.Afterward,the VSeM could be dissociated in response to intracellular ROS to trigger VES/MTX release;then the released VES could produce extra ROS to accelerate the collapse of VSeM.Finally,the excessive ROS produced from VES could synergize with the released MTX to efficiently suppress tumor growth via orchestrated oxidation-chemotherapy.Our study provides a novel strategy to engineer cascade-responsive nanodrug for synergistic cancer treatment.展开更多
Low temperature plasma(LTP)technology has shown an outstanding application value in the pharmaceutical filed in recent ten years.This paper reviews the research advances in LTP,including its effects on enhancing or in...Low temperature plasma(LTP)technology has shown an outstanding application value in the pharmaceutical filed in recent ten years.This paper reviews the research advances in LTP,including its effects on enhancing or inhibiting drug activity,its combined use with drugs to treat cancers,its effects on the improvement of drug delivery system,its use in preparation of new inactivated virus vaccines,its use with mass spectrometry for rapid detection of drug quality,and the anti-tumor and sterilization effects of plasma-activated liquids.The paper also analyzes the challenges of LTP in the pharmaceutical filed,hoping to promote related research.展开更多
Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppre...Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.展开更多
To design a new type of antitumor nanodrug carrier with good biocompatibility, a drug delivery system with a 2.19% drug-loading rate, measured by high-performance liquid chromatography(HPLC), was prepared by membrane ...To design a new type of antitumor nanodrug carrier with good biocompatibility, a drug delivery system with a 2.19% drug-loading rate, measured by high-performance liquid chromatography(HPLC), was prepared by membrane hydration using a mixed polymer: Pluronic■ F-127, which binds folic acid(FA), Pluronic■ F-68 and triptolide(TPL)(FA-F-127/F-68-TPL). As a control, another drug delivery system based on a single polymer(FA-F-127-TPL) with a 1.90% drug-loading rate was prepared by substituting F-68 with F-127. The average particle sizes of FA-F-127/F-68-TPL and FA-F-127-TPL measured by a particle size analyzer were 30.7 nm and 31.6 nm, respectively. Their morphology was observed by atomic force microscopy(AFM). The results showed that FA-F-127-TPL self-assembled into nanomicelles, whereas FA-F-127/F-68-TPL self-assembled into nanogels. An MTT assay showed that a very low concentration of FA-F-127/F-68-TPL or FA-F-127-TPL could significantly inhibit the proliferation of multidrug-resistant(MDR) breast cancer cells(MCF-7/ADR cells) and induce cell death. The effects were significantly different from those of free TPL(P < 0.01). Using the fluorescent probe Nile red(Nr) as the drug model, FA-F-127/F-68-Nr nanogels and FAF-127-Nr nanomicelles were prepared and then incubated with human hepatocarcinoma(HepG2) and MCF-7/ADR cells, and the fluorescence intensity in the cells was measured by a multifunctional microplate reader. The results indicated that both FA-F-127/F-68-Nr and FA-F-127-Nr had sustained release in the cells, but HepG2 and MCF-7/ADR cells exhibited significantly higher endocytosis of FA-F-127/F-68-Nr than that of FA-F-127-Nr(P < 0.01). A nude mice transplanted tumor model was prepared to monitor FA-F-127/F-68-Nr in the tumor tissue and organs by whole-body fluorescent imaging. The results showed that FA-F-127/F-68-Nr targeted tumor tissues. The prepared nanogels had small particle size, were easy to swallow, exhibited slow release property,targeted tumor cells, and could improve the antitumor effects of TPL;hence, they are ideal carriers for low-dose antineoplastic drugs.展开更多
Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and system...Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTXloaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and toxicokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.展开更多
Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new...Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity.Among them,thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection.This smart biomaterial could transform to semisolid phase when the temperature increased.Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe,efficient,and sustained inner ear drug administration.This article introduces the key techniques and the latest progress in this field.展开更多
Cancer stem cells(CSCs)are a small proportion of the cells that exist in cancer tissues.They are considered to be the culprit of tumor genesis,development,drug resistance,metastasis and recurrence because of their sel...Cancer stem cells(CSCs)are a small proportion of the cells that exist in cancer tissues.They are considered to be the culprit of tumor genesis,development,drug resistance,metastasis and recurrence because of their self-renewal,proliferation,and differentiation potential.The elimination of CSCs is thus the key to cure cancer,and targeting CSCs provides a new method for tumor treatment.Due to the advantages of controlled sustained release,targeting and high biocompatibility,a variety of nanomaterials are used in the diagnosis and treatments targeting CSCs and promote the recognition and removal of tumor cells and CSCs.This article mainly reviews the research progress of nanotechnology in sorting CSCs and nanodrug delivery systems targeting CSCs.Furthermore,we identify the problems and future research directions of nanotechnology in CSC therapy.We hope that this review will provide guidance for the design of nanotechnology as a drug carrier so that it can be used in clinic for cancer therapy as soon as possible.展开更多
Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a ty...Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.展开更多
Recently,immunotherapy has redefined cancer treatment by promoting the rapid killing of tumor cells through the immune system.Herbal medicines have been increasingly used as adjunct therapies to complement cancer trea...Recently,immunotherapy has redefined cancer treatment by promoting the rapid killing of tumor cells through the immune system.Herbal medicines have been increasingly used as adjunct therapies to complement cancer treatment along with chemotherapy and radiotherapy to delay tumor development,reduce pain,and prolong patient survival.However,the potential immunotherapeutic effects of these herbal derivatives are limited by their structural instability,poor membrane permeability,and low bioavailability.To address this issue,nanotechnology has been used to enhance the activity of active compounds.Therefore,this review focuses on the effectiveness of the active ingredients of herbal medicines in suppressing tumor progression by modulating both the innate and adaptive immune systems,challenges in their delivery,and the application of nanocarriers for the effective delivery of these herbal components.展开更多
Nanopharmaceuticals containing quantum dot nanoparticles (Q-Dot NPs) for treating serious cancers such as breast cancer have made fantastic proposals. In this study, ZnO quantum dot NPs are formulated via ZnO@PVP nano...Nanopharmaceuticals containing quantum dot nanoparticles (Q-Dot NPs) for treating serious cancers such as breast cancer have made fantastic proposals. In this study, ZnO quantum dot NPs are formulated via ZnO@PVP nanopolymer as co-assistants coordinating with efficacious suitable wetting agents, PEG-binding compound, and W/O emulsifier for producing eco-friendly water-based nanodrug. Several characterization techniques containing SEM, TEM, FTIR, photoluminescence, zeta potential, and UV-Vis absorption were employed for ZnO Q-Dot NPs in nanodrug. This work aims to investigate the anti-tumor effects of such nanomedicine on the 4T1 breast cancer cell line in BALB/c mice, being elaborated through intraperitoneal, injection (IVP) and oral therapy. The impressive findings showed that ZnO nanodrug caused changes in blood factors, having the most effectiveness at 40 μg/ml concentration after two weeks of oral treatments. The significant increase in white blood cells (WBC) neutrophils and meaningful decreases in lymphocytes and especially cholesterol were powerful simultaneous impacts, successfully treating malignant breast cancer masses. In this significant animal model research for breast cancer, the sick mice recovered entirely and even had a safe space to mate. Histopathological results showed no evidence of breast tumor formation or metastasis in the group treated with nanodrug and their children. This nanomedicine has a therapeutic effect, and is ready to be applied for treating volunteer breast cancer patients. However, its prevention (inhibitory) effect can also be analyzed and added to current data in future studies.展开更多
Magnetic stimulation has made significant strides in the treatment of psychiatric disorders.Nonetheless,current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot real...Magnetic stimulation has made significant strides in the treatment of psychiatric disorders.Nonetheless,current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation.To address this,we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration.We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system(pMSS)with repetitive transcranial magnetic stimulation in mice.Oxytocin levels,dendritic morphology and density,and mouse behavior were measured before and after pMSS intervention.Our findings suggest that pMSS can activate oxytocinergic neurons,leading to upregulation of oxytocin secretion and neurite outgrowth.As a result,sociability was rapidly improved after a one-week pMSS treatment regimen.These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.展开更多
The development of sustainable and non-invasive method for delivering drugs to the brain is crucial for the effective treatment of Parkinson’s disease(PD).In this study,nanoparticles were formulated by using poly(eth...The development of sustainable and non-invasive method for delivering drugs to the brain is crucial for the effective treatment of Parkinson’s disease(PD).In this study,nanoparticles were formulated by using poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)(PEG-b-PPG-b-PEG)to facilitate an efficient intranasal delivery of rotigotine directly into the brain.It was found that the intranasal route enabled more effective accumulation of rotigotine in the brain than conventional intravenous administration,demonstrating its feasibility as an innovative delivery approach for PD treatment.Furthermore,the behavioral test,brain histology and immunochemistry analyses demonstrated a significant improvement in the symptoms of PD-like neurodegeneration in mice treated with intranasally delivered rotigotine-loaded nanoparticles.These outcomes affirm an outstanding therapeutic efficacy of the nano-formulation for intranasal delivery,highlighting its potential for the effective treatment of neurodegenerative disorders,particularly PD.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:82474195)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(Grant No.:021093002882)+2 种基金the Youth Medical Innovation Research Project of China(Grant No.:P24021887623)Taizhou Science and Technology Support Project,China(Grant No.:TS202420)grants from Nanjing Medical University,China(Grant Nos.:TZKY20230104 and 2024KF0292).
文摘Respiratory syncytial virus(RSV)is a ubiquitous respiratory virus that affects individuals of all ages;however,there is a notable lack of targeted treatments.RSV infection is associated with a range of respiratory symptoms,including bronchiolitis and pneumonia.Baicalin(BA)exhibits significant therapeutic effects against RSV infection through mechanisms of viral inhibition and anti-inflammatory action.Nonetheless,the clinical application of BA is constrained by its low solubility and bioavailability.In this study,we prepared BA nanodrugs(BA NDs)with enhanced water solubility utilizing the supramolecular self-assembled strategy,and we further conducted a comparative analysis of this pharmacological activity between free drugs and NDs of BA.Both in vitro and in vivo results demonstrated that BA NDs significantly enhanced the dual effects of viral inhibition and inflammation relief compared to free BA,attributed to prolonged lung retention,improved cellular uptake,and increased targeting affinity.Our study confirms that the nanosizing strategy,a straightforward approach to enhance drug solubility,can also increase biological activity compared to free drugs with the same content,thereby providing a potential ND for RSV treatment.This correlation analysis between the existing forms of drugs and their biological activity offers a novel perspective for research on the active ingredients of traditional Chinese medicine.
基金supported by the Young Elite Scientists Sponsorship Program by CACM(No.2022-QNRC2-B12)the Key Project of Anhui Province Department of Education(No.2022AH050528)+2 种基金Anhui Province Key Laboratory(No.2024ZYFBAHKLA11)the Domestic Visiting Project of Anhui Province Department of Education(No.gxgnfx2022015)the National Nature Science Foundation of China(No.82003675).
文摘Rheumatoid arthritis(RA)is a sophisticated autoimmune disorder involving in the pathological characteristics of joint inflammation,synovial hyperplasia,pannus formation,cartilage destruction and bone erosion.Current rheumatic therapy drugs such as non-steroidal anti-inflammatory drugs,glucocorticoids,disease-modifying antirheumatic drugs,or biologics are remarkably restricted by their poor blood circulation capability,unsatisfied drug loading efficiency,off-target irritation,and carrier-related toxicity.Recently,great efforts have concentrated on carrier-free nanoparticulated delivery strategy,and multifarious carrier-free nanodrugs including nanocrystal,nanoparticle,and nanomicelle have been manifested to possess boosted stability,extended circulation capability,enhanced drug accumulation at the inflammatory joint,and high-efficiency and low-toxicity therapeutic outcomes in RA models.Hence,this review provides a comprehensive summary of carrier-free nanodrugs for efficient RA treatment,with an emphasis on nanocrystal,nanoparticle,and nanomicelle,and then the ongoing challenges and prospects of carrier-free nanodrugs are discussed.
基金supported by the Science and Technology Development Program of Jilin Province(Grant Number***202302001)the Science and Technology Development Program of Changchun City(Grant Number 23***13),and the Special Project from MOST of China.
文摘Numerous reports have demonstrated the construction of supramolecular nanodrugs(SNDs)via theπ-πstacking of drug molecules for antitumor applications because most drugs possess aromatic rings or other planar conjugate units.However,the destruction ofπ-πstacking and the subsequent disassembly of SNDs under tumor microenvironment(TME),which is the precondition for drug release,have not been clearly described.In this work,based on a disassembly model ofπ-πstacked naphthoquinone SNDs,the influence of co-assembled drugs on disassembly is delineated.Both the experimental observation and computational simulation indicate that the disassembly of SNDs under simulated TME highly depends on the disassembly activation energy(ΔE_(dis))of neighboringπ-πstacked molecules.Owing to the highΔE_(dis),the disassembly of self-assembled naphthoquinone SNDs is greatly restricted.Meaningfully,theΔE_(dis)is the sum of a series of activation energy according to the specific stimuli of TME.Thus,a concept of stimuli-responsive drug-mates is proposed for boosting the disassembly ofπ-πstacked SNDs,namely the foremost co-assembly ofπ-conjugated drugs with additional drug molecules that possess relatively weakπ-πinteraction but high TME responsiveness.Further computational simulation reveals that the introduction of stimuli-responsive drug-mates significantly lowers theΔE_(dis),thus accelerating the disassembly of SNDs and the release of drug payloads.Holding the advantages ofπ-conjugated drug library,the concept of stimuli-responsive drug-mates gives an extensive design ofπ-πstacked SNDs toward heterogeneous nidus microenvironment responsiveness,which highlights the superiority of widely used drug co-assembly strategy in constructing multifunctional SNDs.
基金supported by grants from the National Key Research and Development Program of China(No.2018YFC1106103)the National Natural Science Foundation of China(Grant No.51973135).
文摘The considerable development of carrier-free nanodrugs has been achieved due to their high drug-loading capability,simple preparation method,and offering“all-in-one”functional platform features.However,the native defects of carrier-free nanodrugs limit their delivery and release behavior throughout the in vivo journey,which significantly compromise the therapeutic efficacy and hinder their further development in cancer treatment.In this review,we summarized and discussed the recent strategies to enhance drug delivery and release of carrier-free nanodrugs for improved cancer therapy,including optimizing the intrinsic physicochemical properties and external modification.Finally,the corresponding challenges that carrier-free nanodrugs faced are discussed and the future perspectives for its application are presented.We hope this review will provide constructive information for the rational design of more effective carrier-free nanodrugs to advance therapeutic treatment.
基金Key Areas Research and Development Program of Guangzhou,Grant/Award Number:202007020006National Natural Science Foundation of China,Grant/Award Numbers:51933011,31971296,52173125,82102194Natural Science Foundation of the Guangdong Province,Grant/Award Numbers:2021A1515111006,2023A1515011822。
文摘Nanodrugs capable of aggregating in the tumor microenvironment(TME)have demonstrated great efficiency in improving the therapeutic outcome.Among vari-ous approaches,the strategy utilizing electrostatic interaction as a driving force to achieve intratumor aggregation of nanodrugs has attracted great attention.However,the great difference between the two nanodrugs with varied physicochemical prop-erties makes their synchronous transport in blood circulation and equal-opportunity tumor uptake impossible,which significantly detracts from the beneficial effects of nanodrug aggregation inside tumors.We herein propose a new strategy to construct a pair of extremely similar nanodrugs,referred to as“twins-like nanodrugs(TLNs)”,which have identical physicochemical properties including the same morphology,size,and electroneutrality to render them the same blood circulation time and tumor entrance.The 1:1 mixture of TLNs(TLNs-Mix)intravenously injected into a mouse model efficiently accumulates in tumor sites and then transfers to oppositely charged nanodrugs for electrostatic interaction-driven coalescence via responding to matrix metalloproteinase-2(MMP-2)enriched in tumor.In addition to enhanced tumor retention,the thus-formed micron-sized aggregates show high echo intensity essen-tial for ultrasound imaging as well as ultrasound-triggered penetrative drug delivery.Owing to their distinctive features,the TLNs-Mix carrying sonosensitizer,immune adjuvant,and ultrasound contrast agent exert potent sonodynamic immunotherapy against hypovascular hepatoma,demonstrating their great potential in treating solid malignancies.
文摘A nanomicelle(denoted as TPGS/Ppa)was fabricated via the coassembly of the amphiphilic D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)and the hydrophobic photosensitizer pyropheophorbide a(Ppa)for photodynamic therapy(PDT).The obtained nanomicelle possessed a spherical structure with a diameter of(18.0±2.2)nm and a zeta potential of approximately -18 mV.Besides,the nanomicelle exhibited excellent photostability,biocompatibility,and phototoxicity,and could effectively reach the tumor region via the enhanced permeability and retention effect.Additionally,it could be found that the TPGS/Ppa nanomicelle exhibited higher phototoxicity against 4T1 murine mammary cancer cells than free Ppa.In the 4T1 tumor-bearing mouse model,the nanomicelle showed an excellent antitumor therapeutic effect.This study develops a new type of photodynamic nanomicelle TPGS/Ppa,which can increase the accumulation of drugs and prolong their tumor retention time,providing a feasible strategy for realizing the delivery of small-molecule hydrophobic drugs and tumor PDT.
基金supported by Young Talent Program of The Affiliated Hospital of Xuzhou Medical University,Advanced Program of The Affiliated Hospital of Xuzhou Medical University(PYJH2024210)Medical Research Project of Jiangsu Provincial Health Commission(H2023050)National Natural Science Foundation of China(No.32301278).
文摘Traditional Chinese medicines(TCMs)have been used for centuries to treat and manage various diseases.However,their effective delivery to targeted sites may be a major challenge due to their poor water solubility,low bio-availability,and potential toxicity.Nanocarriers,such as liposomes,polymeric nanoparticles,inorganic nanoparticles,and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations.This article summarizes the recent progress in nanocarrier-based delivery systems.Nanotechnology can broaden the scope of applications of traditional Chinese medicine.The concept of nano-traditional Chinese medicine(nano-TCM)is introduced,and the progress of nanomedicine,the advantages,and the development direction of nano-TCM are reviewed,providing new ideas for the development of nano-TCM.
基金supported by the Key Research and Development Program in the Xinjiang Uygur Autonomous Region(No.2023B02030-1)the National Natural Science Foundation of China(No.82560364).
文摘Although nanodrugs based on antiangiogenic and oxidative stress have received widespread attention in oncotherapy,low delivery efficiency and drug payload have greatly hindered their further applications.The self-targeting carrier-free metal-organic nanodrugs are constructed via the dynamic ligand-driven self-assembly of anti-angiogenesis pseudolaric acid B(PAB),Fenton-like agent copper ion,and the chemo-drug pemetrexed(PEM)to enhance anti-angiogenic-oxidative stress oncotherapy.After intravenous injection,it is found that such nanodrugs can be efficiently accumulated in tumor site and internalized into tumor cells by folate receptors-mediated self-targeting.After that,nanodrugs are disassembled to achieve the burst release of drugs under stimuli of acidic lysosome and endogenous glutathione(GSH).Interestingly,the released Cu[II]can efficiently decompose the endogenous hydrogen peroxide(H2O2)into hydroxyl radicals(·OH)and significantly weaken reactive oxygen species(ROS)elimination by downregulating endogenous GSH to self-amplify intracellular oxidative stress.Meanwhile,the released PAB can obviously inhibit the secretion of vascular endothelial growth factor(VEGF),block the formation of new blood vessels,and regulate the conformation of VEGF receptor 2(VEGFR2)to inhibit the angiogenesis signaling pathway.After two weeks of treatment,PEM-Cu[II]-PAB(PCP)nanodrugs achieved a 95%tumor inhibition rate and 100%survival rate in tumor-bearing mice.Taken together,our study can expect to provide a promising method for targeted oncotherapy based on the synergistic therapy of antiangiogenic or oxidative stress.
基金This work was partially supported by the National Natural Science Foundation of China(Grant Nos.81871483,81671813 and 61727823)the open project funding of The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province(Grant No.2018ZDSY2001).
文摘Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions.Herein,we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation followed by circularly amplified ROS-triggered drug release via positive-feedback loop.The di-selenide-bridged prodrug synthesized from vitamin E succinate and methotrexate(MTX)self-assembles into nanoparticles(VSeM);decorating acidity-cleavable PEG onto VSeM surface temporarily shields the targeting ability of MTX to evade immune clearance and consequently elongate circulation time.Upon reaching tumor sites,acidity-triggered detachment of PEG results in targeting recovery to enhance tumor cell uptake.Afterward,the VSeM could be dissociated in response to intracellular ROS to trigger VES/MTX release;then the released VES could produce extra ROS to accelerate the collapse of VSeM.Finally,the excessive ROS produced from VES could synergize with the released MTX to efficiently suppress tumor growth via orchestrated oxidation-chemotherapy.Our study provides a novel strategy to engineer cascade-responsive nanodrug for synergistic cancer treatment.
基金supported by the National Natural Science Foundation of China(Grant No.51677146)Project of Independent Innovative Experiment for Postgraduates in Medicine in Xi’an Jiaotong University(Grant No.JSCX-2018-014)the Special Scientific Research Project Funds of Shaanxi Province(Grant No.18JK1102).
文摘Low temperature plasma(LTP)technology has shown an outstanding application value in the pharmaceutical filed in recent ten years.This paper reviews the research advances in LTP,including its effects on enhancing or inhibiting drug activity,its combined use with drugs to treat cancers,its effects on the improvement of drug delivery system,its use in preparation of new inactivated virus vaccines,its use with mass spectrometry for rapid detection of drug quality,and the anti-tumor and sterilization effects of plasma-activated liquids.The paper also analyzes the challenges of LTP in the pharmaceutical filed,hoping to promote related research.
文摘Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis.Immunotherapy has shown great potential in the treatment of osteosarcoma.However,the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment.The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment.Here,we prepared a dual pH-sensitive nanocarrier,loaded with the photosensitizer Chlorin e6(Ce6)and CD47 monoclonal antibodies(aCD47),to deliver synergistic photodynamic and immunotherapy of osteosarcoma.On laser irradiation,Ce6 can generate reactive oxygen species(ROS)to kill cancer cells directly and induces immunogenic tumor cell death(ICD),which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47.Moreover,both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages,promote antigen presentation,and eventually induce T lymphocyte-mediated antitumor immunity.Overall,the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma,which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.
基金Funded by the National Natural Science Foundation of Hubei Province(No.2014CFB306)the National Natural Science Foundation of China(No.51772233)+1 种基金the National Key Research and Development Program of China(No.2016YFC1101605)the Science and Technology Support Program of Hubei Province(No.2015BAA085)
文摘To design a new type of antitumor nanodrug carrier with good biocompatibility, a drug delivery system with a 2.19% drug-loading rate, measured by high-performance liquid chromatography(HPLC), was prepared by membrane hydration using a mixed polymer: Pluronic■ F-127, which binds folic acid(FA), Pluronic■ F-68 and triptolide(TPL)(FA-F-127/F-68-TPL). As a control, another drug delivery system based on a single polymer(FA-F-127-TPL) with a 1.90% drug-loading rate was prepared by substituting F-68 with F-127. The average particle sizes of FA-F-127/F-68-TPL and FA-F-127-TPL measured by a particle size analyzer were 30.7 nm and 31.6 nm, respectively. Their morphology was observed by atomic force microscopy(AFM). The results showed that FA-F-127-TPL self-assembled into nanomicelles, whereas FA-F-127/F-68-TPL self-assembled into nanogels. An MTT assay showed that a very low concentration of FA-F-127/F-68-TPL or FA-F-127-TPL could significantly inhibit the proliferation of multidrug-resistant(MDR) breast cancer cells(MCF-7/ADR cells) and induce cell death. The effects were significantly different from those of free TPL(P < 0.01). Using the fluorescent probe Nile red(Nr) as the drug model, FA-F-127/F-68-Nr nanogels and FAF-127-Nr nanomicelles were prepared and then incubated with human hepatocarcinoma(HepG2) and MCF-7/ADR cells, and the fluorescence intensity in the cells was measured by a multifunctional microplate reader. The results indicated that both FA-F-127/F-68-Nr and FA-F-127-Nr had sustained release in the cells, but HepG2 and MCF-7/ADR cells exhibited significantly higher endocytosis of FA-F-127/F-68-Nr than that of FA-F-127-Nr(P < 0.01). A nude mice transplanted tumor model was prepared to monitor FA-F-127/F-68-Nr in the tumor tissue and organs by whole-body fluorescent imaging. The results showed that FA-F-127/F-68-Nr targeted tumor tissues. The prepared nanogels had small particle size, were easy to swallow, exhibited slow release property,targeted tumor cells, and could improve the antitumor effects of TPL;hence, they are ideal carriers for low-dose antineoplastic drugs.
基金supported by the National Science and Technology Major Project of China(Grant No.:2018ZX09711001)Beijing Nova Program(Grant No.:Z211100002121127)+2 种基金Beijing Natural Science Foundation(Grant No.:L212059)Fundamental Research Funds for the Central Universities(Grant No.:3332021101)CAMS Innovation Fund for Medical Sciences(CIFMS,Grant No.:2022-I2M-JB-011).
文摘Lipid nanoemulsions are promising nanodrug delivery carriers that can improve the efficacy and safety of paclitaxel(PTX).However,no intravenous lipid emulsion of PTX has been approved for clinical treatment,and systemic safety profiles have not yet been reported.Here we outline the development of a PTXloaded tumor-targeting intravenous lipid emulsion(PTX Emul)and describe its characteristics,colloidal stability,and systemic safety profiles in terms of acute toxicity,long-term toxicity,and toxicokinetics.We also compare PTX Emul with conventional PTX injection.Results showed that PTX Emul exhibited an ideal average particle size(approximately 160 nm)with narrow size distribution and robust colloidal stability under different conditions.Hypersensitivity reaction and hemolysis tests revealed that PTX Emul did not induce hypersensitivity reactions and had no hemolytic potential.In addition,where the alleviated systemic toxicity of PTX Emul may be attributed to the altered toxicokinetic characteristics in beagle dogs,including the decreased AUC and increased plasma clearance and volume of distribution,PTX Emul alleviated acute and long-term toxicity as evidenced by the enhanced the median lethal dose and approximate lethal dose,moderate body weight change,decreased bone marrow suppression and organ toxicity compared with those under PTX injection at the same dose.A fundamental understanding of the systemic safety profiles,high tumor-targeting efficiency,and superior antitumor activity in vivo of PTX Emul can provide powerful evidence of its therapeutic potential as a future treatment for breast cancer.
基金supported by the national key R&D program(2022YFC2402703).
文摘Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity.Among them,thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection.This smart biomaterial could transform to semisolid phase when the temperature increased.Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe,efficient,and sustained inner ear drug administration.This article introduces the key techniques and the latest progress in this field.
基金Natural Science Foundation of Nanjing University of Chinese Medicine China,No.XZR2020093.
文摘Cancer stem cells(CSCs)are a small proportion of the cells that exist in cancer tissues.They are considered to be the culprit of tumor genesis,development,drug resistance,metastasis and recurrence because of their self-renewal,proliferation,and differentiation potential.The elimination of CSCs is thus the key to cure cancer,and targeting CSCs provides a new method for tumor treatment.Due to the advantages of controlled sustained release,targeting and high biocompatibility,a variety of nanomaterials are used in the diagnosis and treatments targeting CSCs and promote the recognition and removal of tumor cells and CSCs.This article mainly reviews the research progress of nanotechnology in sorting CSCs and nanodrug delivery systems targeting CSCs.Furthermore,we identify the problems and future research directions of nanotechnology in CSC therapy.We hope that this review will provide guidance for the design of nanotechnology as a drug carrier so that it can be used in clinic for cancer therapy as soon as possible.
文摘Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.
基金the National Natural Science Foundation of China(82260695,82360781)the Jiangxi Provincial Natural Science Foundation(20232ACB206062)+4 种基金Jiangxi Provincial Department of Education(GJJ2400823)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202207)Young Jinggang Scholar of Jiangxi Province(Jing Zhang)and New Century Talents Project of Jiangxi Province(2017082,Xiang Li and 2020028,Jing Zhang)the Science and Technology Innovation Team of Jiangxi University of Chinese Medicine(CXTD22001 and CXTD22006)Jiangxi University of Traditional Chinese Medicine Special Zone Construction Project of Traditional Chinese Medicine(New Drug Creation Direction)(TQ-20).
文摘Recently,immunotherapy has redefined cancer treatment by promoting the rapid killing of tumor cells through the immune system.Herbal medicines have been increasingly used as adjunct therapies to complement cancer treatment along with chemotherapy and radiotherapy to delay tumor development,reduce pain,and prolong patient survival.However,the potential immunotherapeutic effects of these herbal derivatives are limited by their structural instability,poor membrane permeability,and low bioavailability.To address this issue,nanotechnology has been used to enhance the activity of active compounds.Therefore,this review focuses on the effectiveness of the active ingredients of herbal medicines in suppressing tumor progression by modulating both the innate and adaptive immune systems,challenges in their delivery,and the application of nanocarriers for the effective delivery of these herbal components.
文摘Nanopharmaceuticals containing quantum dot nanoparticles (Q-Dot NPs) for treating serious cancers such as breast cancer have made fantastic proposals. In this study, ZnO quantum dot NPs are formulated via ZnO@PVP nanopolymer as co-assistants coordinating with efficacious suitable wetting agents, PEG-binding compound, and W/O emulsifier for producing eco-friendly water-based nanodrug. Several characterization techniques containing SEM, TEM, FTIR, photoluminescence, zeta potential, and UV-Vis absorption were employed for ZnO Q-Dot NPs in nanodrug. This work aims to investigate the anti-tumor effects of such nanomedicine on the 4T1 breast cancer cell line in BALB/c mice, being elaborated through intraperitoneal, injection (IVP) and oral therapy. The impressive findings showed that ZnO nanodrug caused changes in blood factors, having the most effectiveness at 40 μg/ml concentration after two weeks of oral treatments. The significant increase in white blood cells (WBC) neutrophils and meaningful decreases in lymphocytes and especially cholesterol were powerful simultaneous impacts, successfully treating malignant breast cancer masses. In this significant animal model research for breast cancer, the sick mice recovered entirely and even had a safe space to mate. Histopathological results showed no evidence of breast tumor formation or metastasis in the group treated with nanodrug and their children. This nanomedicine has a therapeutic effect, and is ready to be applied for treating volunteer breast cancer patients. However, its prevention (inhibitory) effect can also be analyzed and added to current data in future studies.
基金supported by the China Science and Technology Innovation 2030-Major Project(2022ZD0211700)the Major Program of the National Natural Science Foundation of China(62394312)+2 种基金the National Natural Science Foundation of China(82471536)the Wenzhou Science and Technology Projects(ZY2023006,2024R2002)Oujiang Laboratory(OJQD2022002).
文摘Magnetic stimulation has made significant strides in the treatment of psychiatric disorders.Nonetheless,current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation.To address this,we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration.We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system(pMSS)with repetitive transcranial magnetic stimulation in mice.Oxytocin levels,dendritic morphology and density,and mouse behavior were measured before and after pMSS intervention.Our findings suggest that pMSS can activate oxytocinergic neurons,leading to upregulation of oxytocin secretion and neurite outgrowth.As a result,sociability was rapidly improved after a one-week pMSS treatment regimen.These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
基金fnancial support from the National Natural Science Foundation of China(82130059,82222033,82172003)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘The development of sustainable and non-invasive method for delivering drugs to the brain is crucial for the effective treatment of Parkinson’s disease(PD).In this study,nanoparticles were formulated by using poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol)(PEG-b-PPG-b-PEG)to facilitate an efficient intranasal delivery of rotigotine directly into the brain.It was found that the intranasal route enabled more effective accumulation of rotigotine in the brain than conventional intravenous administration,demonstrating its feasibility as an innovative delivery approach for PD treatment.Furthermore,the behavioral test,brain histology and immunochemistry analyses demonstrated a significant improvement in the symptoms of PD-like neurodegeneration in mice treated with intranasally delivered rotigotine-loaded nanoparticles.These outcomes affirm an outstanding therapeutic efficacy of the nano-formulation for intranasal delivery,highlighting its potential for the effective treatment of neurodegenerative disorders,particularly PD.
