Asthma, one of the most prevalent chronic inflammatory diseases, remains challenging to manage effectively. Current therapies commonly alleviate symptoms through broad immunosuppression and bronchodilation but fail to...Asthma, one of the most prevalent chronic inflammatory diseases, remains challenging to manage effectively. Current therapies commonly alleviate symptoms through broad immunosuppression and bronchodilation but fail to target disease-specific molecular pathways. Genetic intervention using small interfering RNA(siRNA) has emerged as a promising strategy for asthma therapy. However, its success is largely hindered by the lack of an efficient delivery approach targeting airway epithelial cells(AECs). Here, we developed a novel inhalable siRNA delivery system based on artificially prepared nanovesicles through designed extrusion processes of mesenchymal stem cells. To enable an effective inhalation delivery of siRNA via nanovesicles, various parameters, including extrusion cycles,membrane pore sizes, and centrifugal forces were examined through orthogonal testing.Results revealed that the artificially prepared nanovesicles demonstrated remarkable capability to deliver thymic stromal lymphopoietin-targeted siRNA into AECs and substantially suppressed the inflammatory pathways and goblet cell hyperplasia, and eventually achieved a significant inhibition of asthma symptoms in ovalbumin-induced asthma models. Thus, the present study provides a novel nebulized nanovesicle-based carrier for effective delivery of siRNA through local inhalation, offering a promising therapeutic delivery platform for asthma and potentially other respiratory diseases.展开更多
Established evidence has unveiled two strategies for treating cancer:depleting tumor-associated macrophages(TAMs)and reprogramming M2-like TAMs into an antitumor M1 phenotype.Here,we designed novel p H-sensitive biomi...Established evidence has unveiled two strategies for treating cancer:depleting tumor-associated macrophages(TAMs)and reprogramming M2-like TAMs into an antitumor M1 phenotype.Here,we designed novel p H-sensitive biomimetic hybrid nanovesicles(EDHPA)loaded with doxorubicin(DOX).DOX@EDHPA can specifically target TAMs by activating macrophage-derived exosomes(M1-Exos)and anisamide(AA)as cancer-specific targeting ligands.In vitro and in vivo studies demonstrated that DOX@EDHPA could efficiently be delivered to the tumor site and taken up by cells.Meanwhile,it synergistically enhanced immunogenic cell death(ICD)and induced a subsequent antigen-specific T cell immune response.The tumor inhibitory rate of the DOX@EDHPA group was 1.42 times that of the free DOX group.Further analysis showed that the excellent antitumor effects of DOX@EDHPA should ascribe to the homing effect of M1-Exos on macrophages and the repolarization to antitumor M1 TAMs,which induced the elevated secretion of pro-infiammatory factors.Therefore,the hybrid EDHPA targeting TAMs to reshape the tumor microenvironment constituted a novel immunochemotherapy strategy to inhibit tumor growth.展开更多
Metabolic dysfunction-associated fatty liver disease(MASLD)and alcohol-associated liver disease(ALD)are prevalent chronic liver diseases that can progress to steatohepatitis,fibrosis,cirrhosis,and ultimately liver fai...Metabolic dysfunction-associated fatty liver disease(MASLD)and alcohol-associated liver disease(ALD)are prevalent chronic liver diseases that can progress to steatohepatitis,fibrosis,cirrhosis,and ultimately liver failure.Here,we demonstrated that oral administration of GNVs provided substantial protection against liver injury and fibrosis in MASLD and ALD mouse models.In a Western-style high-fat diet-induced MASLD model and a chronic binge alcohol-induced ALD model,GNVs treatment significantly reduced gut leakiness by restoring intestinal junctional complex proteins and rebalancing the gut microbiome.GNVs attenuated hepatic lipid accumulation,oxidative stress and fibrogenicmarkers.GNV treatment downregulated the fibrosis-associated tissue inhibitor of metalloproteinase-2(TIMP2)pathway in hepatic stellate cells,which is linked to enhanced matrix degradation and reduced fibrogenesis.GNVs prevent MASLD-and ALD-associated gut barrier dysfunction and liver fibrosis through modulation of the gut-liver axis and the TIMP2 pathway.Edible GNVs represent a novel,multifaceted therapeutic strategy for managing chronic liver diseases.展开更多
Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost,sustainability,and tissue targeting.Thus,they hold promise for disease treatment and drug d...Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost,sustainability,and tissue targeting.Thus,they hold promise for disease treatment and drug delivery.In this study,we proposed a time-efficient method,PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles(GDNVs).Subsequently,curcumin(CUR)was loaded onto GDNV by ultrasonic incubation.The optimum conditions for ginger-derived nanovesicles loaded with curcumin(CG)were ultrasound time of 3 min,a carrier-to-drug ratio(GDNV:CUR)of 1:1.The study achieved a high loading capacity(94.027%±0.094%)and encapsulation efficiency(89.300%±0.344%).Finally,the drugs'in vivo distribution and anti-colitis activity were investigated in mice.CG was primarily distributed in the colon after oral administration.Compared to CUR and GDNV,CG was superior in improving disease activity,colon length,liver and spleen coefficients,myeloperoxidase activity,and biochemical factor levels in ulcerative colitis(UC)mice.In addition,CG plays a protective role against UC by modulating serum metabolite levels and gut flora.In summary,our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.展开更多
AIM:To investigate the preparation,physicochemical characterization and cytotoxicity in vitro of Gemcitabine-loaded poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-PDLLA) nanovesicles. METHODS:The nanovesicle carri...AIM:To investigate the preparation,physicochemical characterization and cytotoxicity in vitro of Gemcitabine-loaded poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-PDLLA) nanovesicles. METHODS:The nanovesicle carriers were prepared from the amphiphilic block copolymer of PEG-PDLLA by a double emulsion technique,and gemcitabine was used as the model drug. The morphology of the nanovesicles was determined by scanning and transmission electron microscopy,and the drug content,drug entrapment and drug-release curve in vitro were detected by UV-Vis-NIR spectrophotometry. Cytotoxicity in the human pancreatic cancer cell line SW1990 was tested by 3-(4,5-dimethyl) ethiazole (MTT) assay.RESULTS:The gemcitabine-loaded nanovesicles were hollow nanospheres with a mean size of 200.6 nm,drugloading of 4.14% and drug embedding ratio of 20.54%. The nanovesicles showed excellent controlled release that was characterized by a fast initial release during the first 72 h,followed by a slower and continuous release. The MTT assay demonstrated that gemcitabine-loaded nanovesicles exhibited dose-dependent and time-delayed cytotoxicity in the human pancreatic cancer cell line SW1990.CONCLUSION:Gemcitabine-loaded PEG-PDLLA nanovesicles prepared by a double emulsion technique exhibited good performance for controlled drug release,and had similar cytotoxic activity to free gem-citabine.展开更多
Gold nanovesicles(GVs) with unique plasmonic property and large cavity hold great potential as a stimuli-responsive nanocarrier to deliver drugs for efficient tumor chemotherapy and other therapies synergistically.Her...Gold nanovesicles(GVs) with unique plasmonic property and large cavity hold great potential as a stimuli-responsive nanocarrier to deliver drugs for efficient tumor chemotherapy and other therapies synergistically.Herein,we developed doxorubicin-loaded gold nanovesicles(DGVs),offering infrared thermal(IRT) and photoacoustic(PA) dual-modal imaging guided mild hype rthermia-enhanced chemophotothermal cancer synergistic therapy.The DGVs are self-assembled by gold nanoparticles modified with amphiphilic copolymer in a predetermined concentration of doxorubicin through film rehydration method.Under the influence of laser excitation,the as-prepared DGVs exhibited good photothermal effect,which triggered the structural disruption of GVs and thus,allowed the efficient release of encapsulated DOX to enhance cell uptake for fluorescence imaging and tumor chemotherapy,respectively.In addition,DGVs also showed a strong PA and IRT signals in vivo.Our study demonstrated the potential of DGVs as stimuli-responsive drug delivery systems and cancer theranostics.展开更多
Squamous cell carcinoma (SCC) and melanoma are malignant human cancers of the skin with an annual mortality that exceeds 10,000 cases every year in the USA alone. In this study, the lysosomal protein saposin C (SapC) ...Squamous cell carcinoma (SCC) and melanoma are malignant human cancers of the skin with an annual mortality that exceeds 10,000 cases every year in the USA alone. In this study, the lysosomal protein saposin C (SapC) and the phospholipid dioloylphosphatidylserine (DOPS) were assembled into cancer-selective nanovesicles (SapC-DOPS) and successfully tested using several in vitro and in vivo skin cancer models. Using MTT assay that measures the percentage of cell death, SapC-DOPS cytotoxic effect on three skin tumor cell lines (squamous cell carcinoma, SK-MEL-28, and MeWo) was compared to two normal nontumorigenic skin cells lines, normal immortalized keratinocyte (NIK) and human fibroblast cell (HFC). We observed that the nanovesicles selectively killed the skin cancer cells by inducing apoptotic cell death whereas untransformed skin cancer cells remained unaffected. Using subcutaneous skin tumor xenografts, animals treated with SapC-DOPS by subcutaneous injection showed a 79.4% by volume tumor reduced compared to the control after 4 days of treatment. We observed that the nanovesicles killed skin cancer cells by inducing apoptotic cell death compared to the control as revealed by TUNEL staining of xenograft tumor sections.展开更多
Herbal medicine(HM)has been extensively researched and widely used since ancient times.Currently,as one of the emerging directions in HM modernization research,herbal medicine-derived nanovesicles(HMDNV),a type of nan...Herbal medicine(HM)has been extensively researched and widely used since ancient times.Currently,as one of the emerging directions in HM modernization research,herbal medicine-derived nanovesicles(HMDNV),a type of nanoparticle obtained from destructed plant tissues,hold considerable promise for disease treatment and drug delivery.The recent studies related to HMDNV and miRNAs are summarized in this review,with a special emphasis on their basic characteristics and biological activities,to provide ideas for future scientific research on HMDNV and enrich the content of active components of Traditional Chinese Medicine(TCM).展开更多
Oligonucleotide therapeutics have great potential to target the currently undruggable genes and to generate entirely new therapeutic paradigms in multiple types of disease,thus having attracted much attention in recen...Oligonucleotide therapeutics have great potential to target the currently undruggable genes and to generate entirely new therapeutic paradigms in multiple types of disease,thus having attracted much attention in recent years.However,their applications are greatly hindered by a lack of safe and efficient oligonucleotide-delivery vectors.Polyplex nanovesicles formed from oligonucleotides and the cationic block have shown exceptional features for the delivery of therapeutic oligonucleotides and other biopharmaceuticals.Nevertheless,these polyplex nanovesicles are deeply fraught with difficulty in tolerating physiological ionic strength.Inspired by the high binding ability between the dipicolylamine(DPA)/zinc(Ⅱ)complex and the phosphodiester moieties of oligonucleotides,herein,we designed a coordinative cationic block to solve the intrinsic stability dilemma.Moreover,we found the stability of the resulted polyplex nanovesicles could be easily tuned by the content of coordinated zinc ions.In vitro cellular studies implied that the prepared zinc(Ⅱ)-coordinative polyplex nanovesicles preferred to retain in the lysosomes upon internalization,making them ideal delivery candidates for the lysosome-targeting oligonucleotide therapeutics.展开更多
Lipidic nanovesicles (so called liposomes) were one the earliest forms of nanovectors. One of their limits was our lack of knowledge on the delivery pathway of their content to the target cell cytoplasm. The present c...Lipidic nanovesicles (so called liposomes) were one the earliest forms of nanovectors. One of their limits was our lack of knowledge on the delivery pathway of their content to the target cell cytoplasm. The present communication describes an efficient way to enhance the delivery. Pulsed electric fields (PEF) are known since the early 80’s to mediate a fusogenic state of plasma membranes when applied to a cell suspension or a tissue. Polykaryons are detected when PEF are applied on cells in contact during or after the pulses. Heterofusion can be obtained when a cell mixture is pulsed. When lipidic nanovesicles, either small unilamellar vesicles (SUVs) or large unilamellar vesicles (LUVs), are electrostatically brought in contact with electropermeabilized cells by a salt bridge, their content is delivered into the cytoplasm in electropermeabilized cells. The PEF parameters are selected to affect specifically the cells leaving the vesicles unaffected. It is the electropermeabilized state of the cell membrane that is the trigger of the merging between the plasma membrane and the lipid bilayer. The present investigation shows that the transfer of macromolecules can be obtained;i.e. 20 kD dextrans can be easily transferred while a direct transfer does not take place under the same electrical parameters. Cell viability was not affected by the treatment. As delivery is present only on electropermeabilized cells, a targeting of the effect is obtained in the volume where the PEF parameters are over the critical value for electropermeabilization. A homogeneous cytoplasm labeling is observed under digitised videomicroscopy. The process is a content and “membrane” mixing, following neither a kiss and run or an endocytotic pathway.展开更多
Extracellular vesicles(EVs)are naturally occurring,phospholipid bilayer-enclosed vesicles that offer high bioavailability and minimal invasiveness,making them promising candidates for disease treatment,drug delivery v...Extracellular vesicles(EVs)are naturally occurring,phospholipid bilayer-enclosed vesicles that offer high bioavailability and minimal invasiveness,making them promising candidates for disease treatment,drug delivery vectors,and effective biomarkers for disease detection and diagnosis.As researchers continue to discover and characterize EVs from various origins and biogenesis,their role in intercellular communication for diagnostic and therapeutic purposes becomes increasingly clear.Plant-derived exosome-like nanovesicles(PELNs)are of particular interest due to their compatibility,low toxicity,high bioavailability,ease of absorption,and inherent therapeutic activities.Among the diverse plant sources,lemons stand out for their high nutritional value and wealth of phytochemicals and bioactive components.Recently,there has been significant research into PELNs,focusing on their pharmacological properties and potential applications in drug delivery.This review centres on lemon-derived exosome-like nanovesicles(LELNs),exploring their extraction methods,biological and therapeutic potential,and applications as effective drug delivery systems.By highlighting these aspects,we aim to encourage further research into LELNs to uncover additional properties and potential biomedical applications.展开更多
Myelosuppression is a common and severe side effect of cancer chemotherapy,with current treatments hindered by limitations such as depletion of hematopoietic reserves,poor patient compliance,delayed therapeutic onset,...Myelosuppression is a common and severe side effect of cancer chemotherapy,with current treatments hindered by limitations such as depletion of hematopoietic reserves,poor patient compliance,delayed therapeutic onset,and high cost.To overcome these challenges,we developed Epimedium-derived nanovesicles(ENVs)from the traditional Chinese medicinal herb Epimedium,addressing the solubility and bioavailability issues associated with conventional extracts.ENVs encapsulate bioactive constituents,including icariin and hematopoiesis-promoting ceramides.In a cyclophosphamide(CTX)-induced myelosuppression mouse model,prophylactic and therapeutic oral administration of ENVs effectively alleviated hematopoietic suppression,significantly outperforming the Epimedium-based herbal extract“Joungal”(Shengbai Formula)despite equivalent icariin content.Notably,ENVs promoted hematopoietic stem cell(HSC)proliferation—an outcome rarely achieved with existing therapies.Mechanistically,ENVs modulated the gut microbiota,enriching lactobacillus species and enhancing lactate production.This microbiota-driven lactate signaling stimulated LepR+mesenchymal stem cells(MSCs)in the bone marrow niche to secrete stromal cellderived factor-1(SDF-1)and stem cell factor(SCF),thereby supporting HSC expansion and restoring hematopoietic function.In vivo safety evaluations confirmed the excellent biocompatibility of ENVs.Our findings uncover a gut-lactate-bone marrow axis through which ENVs enhance hematopoiesis and promote HSC regeneration.This work introduces a cost-effective,scalable,and orally administrable biomaterial platform with strong translational potential for the prevention and treatment of chemotherapy-induced myelosuppression.展开更多
Objective:To explore the potential of honeysuckle-derived exosome-like nanovesicles(HELNVs)for preventing cisplatin-induced acute kidney injury(AKI).Methods:The renoprotective efficacy of HELNVs against cisplatin-indu...Objective:To explore the potential of honeysuckle-derived exosome-like nanovesicles(HELNVs)for preventing cisplatin-induced acute kidney injury(AKI).Methods:The renoprotective efficacy of HELNVs against cisplatin-induced AKI was assessed in human kidney cell-2(HK-2)cells exposed to 100μmol/L cisplatin for 24 h,followed by HELNVs(50-200μg/mL)for another 24 h;the optimal therapeutic concentration was determined as 100μg/mL.At this concentration,oxygen species(ROS)levels were measured by flow cytometry.Male C57BL/6 mice received a single intraperitoneal injection of cisplatin(30 mg/kg)to establish an AKI model and were then computer-randomized into 3 groups(n=6 per group):control group,daily intraperitoneal administration of normal saline(0.9%NaCl);the cisplatin-injured group,same NaCl regimen;the HELNVs treatment group,daily intraperitoneal administration of HELNVs(30 mg/kg)for 5 consecutive days,with euthanasia on day 6.Renal accumulation of HELNVs was tracked by small-animal multispectral imaging(peak uptakee at 8-10h).Functional assessment included serum creatinine and blood urea nitrogen(BUN)quantified with an automated biochemical analyzer.Molecular analyses included enzyme-linked immunosorbent assay(ELISA)quantification of interleukin(IL)-1β,IL-6,IL-10,and tumor necrosis factor-α(TNF-α).Results:HELNVs significantly reduced ROS,inflammatory responses,and apoptosis in cisplatin-treated HK-2 cells(P<0.01).In cisplatin-induced AKI mice,HELNVs were efficiently absorbed by kidney cells,effectively prevented oxidative damage and mitochondrial dysfunction(P<0.01).Following treatment with 30 mg/kg HELNVs,serum creatinine and BUN levels were markedly reduced(P<0.01).ELISA results showed decreased levels of IL-1β,IL-6,and TNF-α,along with up-regulated IL-10(P<0.01).Conclusion:HELNVs may serve as a promising therapeutic approach for ameliorating cisplatininduced AKI,offering a potential novel treatment option for managing this condition in clinical settings.展开更多
Human appetite is tightly regulated by Ghrelin(GHRL),a 28aa peptide hormone.In an empty stomach,GHRL is secreted by the stomach epithelial glandular cells which acts on the hypothalamus,leading to appetite stimulation...Human appetite is tightly regulated by Ghrelin(GHRL),a 28aa peptide hormone.In an empty stomach,GHRL is secreted by the stomach epithelial glandular cells which acts on the hypothalamus,leading to appetite stimulation and food intake.Loss of appetite,known as anorexia is a debilitating problem in patients undergoing chemotherapy as well as soldiers working at high altitudes(HA),primarily caused by lower plasma GHRL.Though restoration of plasma GHRL may re-establish appetite,naked GHRL delivery via enteral route is not possible due to its degradation in the gastrointestinal(GI)tract while parenteral route administration is discouraged due to its low plasma half-life.Plant-derived nanovesicles(PDNVs)are exosome-mimetic vesicles naturally present in plants.PDNVs are emerging as natural nanocarriers for the delivery of distinct cargoes for both in vitro and in vivo applications.Cardamom seeds are a nutraceutical spice with known appetite-stimulating attributes.Herein,we encapsulated GHRL peptide in small cardamom-derived PDNVs(SCDNVs)by active sonication and evaluated its in vitro bioavailability and gastrointestinal stability.SCDNVs exhibited high encapsulation efficiency for GHRL and were non-toxic to Caco-2 cells.Compared to native GHRL,SCDNVencapsulated GHRL displayed better intracellular delivery potential in Caco2 cells and was resistance to the simulated gastrointestinal digestion process in vitro.Further,SCDNVs also possessed appetite-stimulating phytochemicals such asα-terpinyl acetate andα-terpinol.Hence,GHRL-encapsulated SCDNVs represent a synergistic cocktail of an appetite-inducing hormone and phytochemicals in bioavailable form for anorexia therapy.展开更多
Membrane-derived biomimetic nanovesicles have emerged as a promising platform in cancer immunotherapy due to their intrinsic biocompatibility,functional plasticity,and capability to modulate immune responses.By integr...Membrane-derived biomimetic nanovesicles have emerged as a promising platform in cancer immunotherapy due to their intrinsic biocompatibility,functional plasticity,and capability to modulate immune responses.By integrating various immunotherapeutic agents,including immune checkpoint inhibitors,tumor antigens,and immunostimulatory adjuvants,these vesicles can be engineered to mimic natural immune communication and overcome key barriers in the tumor immune microenvironment.This review summarizes recent advances in the design,functionalization,and application of biomimetic nanovesicles for anti-tumor immunity.We particularly highlight strategies that harness these vesicles to enhance innate and adaptive immune responses,reverse immune suppression,and synergize with existing immunotherapy modalities.Furthermore,we discuss the challenges associated with biosafety,large-scale manufacturing,and clinical translation.Continued innovation in vesicle engineering and immunological modulation will be crucial for transforming biomimetic nanovesicles into viable next-generation cancer immunotherapeutics.展开更多
Alcoholic liver disease(ALD)is a common chronic liver disease worldwide that urgently needs safe and effective strategies.Clams are popular seafood with hepatoprotective effects,while the effective components and mech...Alcoholic liver disease(ALD)is a common chronic liver disease worldwide that urgently needs safe and effective strategies.Clams are popular seafood with hepatoprotective effects,while the effective components and mechanisms remain unclear.Herein,we demonstrated that clam-derived exosome-like nanovesicles(CENs)ameliorated alcohol-induced liver injury by preventing mitochondrial dysfunction and inhibiting mitochondrial apoptotic pathway.Results showed that CENs exhibited exosome-like morphology with a particle size of 120.08±1.60 nm.Mass spectrometry revealed that CENs naturally carry multiple functional lipids and proteins.Furthermore,CENs were found to survive in the gastrointestinal environment and accumulate in the liver of mice following oral administration.Importantly,administration of CENs effectively alleviated alcohol-induced liver injury and hepatocyte death in mice by restoring mitochondrial function,as indicated by increased ATP levels,enhanced mitochondrial complex I activity,and reduced mitochondrial ROS production.Further cell experiments indicated that CENs could be phagocytosed by HepG2 cells and effectively alleviated alcohol-induced hepatocyte apoptosis by inhibiting mitochondrial apoptotic pathway.Collectively,these results indicate that CENs possess potent hepatoprotective properties and may serve as a novel functional ingredient for managing alcoholic liver disease.展开更多
Exosomes are natural nano-size particles secreted by human cells,containing numerous bioactive cargos.Serving as crucial mediators of intercellular communication,exosomes are involved in many physiological and patholo...Exosomes are natural nano-size particles secreted by human cells,containing numerous bioactive cargos.Serving as crucial mediators of intercellular communication,exosomes are involved in many physiological and pathological processes,such as inflammation,tissue injury,cardiovascular diseases,tumorigenesis and tumor development.Exosomes have exhibited promising results in the diagnosis and treatment of cancer,cardiovascular diseases and others.They are a rapidly growing class of drug delivery vehicles with many advantages over conventional synthetic carriers.Exosomes used in therapeutic applications encounter several challenges,such as the lack of tissue targeting capabilities and short residence time.In this review,we discuss recent advances in exosome engineering to improve tissue targeting and describe the current types of engineered exosome-like nanovesicles,and summarize their preclinical applications in the treatment of diseases.Further,we also highlight the latest engineering strategies developed to extend exosomes retention time in vivo and exosome-like nanovesicles.展开更多
Dysregulated autophagy is a hallmark of Alzheimer’s disease(AD),yet the extent of impairment in macroautophagy and chaperonemediated autophagy(CMA)remains unclear.Here,we show that both pathways are disrupted in AD m...Dysregulated autophagy is a hallmark of Alzheimer’s disease(AD),yet the extent of impairment in macroautophagy and chaperonemediated autophagy(CMA)remains unclear.Here,we show that both pathways are disrupted in AD model mice,precedingβ-amyloid accumulation and driving disease progression.However,therapeutic autophagy modulation is severely restricted by the blood–brain barrier(BBB).To overcome this,we developed Microglia-Liposome Fusion Extrusion(MiLi-FE),a method to engineer microglia-derived nanovesicles(AR@ENV)for the codelivery of AR7(a CMA inducer)and rapamycin(a macroautophagy inducer).Leveraging its microglial membrane origin,AR@ENV effectively crosses the BBB and targets inflammatory sites in the AD brain,where it is internalized by neurons.Once inside,they synchronously activate both autophagy pathways:AR7 antagonizes retinoic acid receptor alpha(RARα)to enhance CMA,while rapamycin inhibits mTOR to promote macroautophagy.This coordinated activation enhances clearance ofβ-amyloid and other toxic aggregates,restores proteostasis,and provides robust neuroprotection.Furthermore,the strategy ameliorates neuroinflammation and significantly rescues cognitive deficits in two distinct AD mouse models.By integrating synchronized dual autophagy activation with targeted biomimetic delivery,AR@ENV represents a promising therapeutic candidate for AD.Moreover,the MiLi-FE platform offers a versatile and scalable approach for delivering diverse therapeutics to the central nervous system,extending its potential applicability to a range of neurological disorders.展开更多
Stroke remains one of the leading causes of adult disability worldwide,with neovascularization is crucial for brain repair after stroke.However,neutrophil infiltration hinders effective neovascularization,necessitatin...Stroke remains one of the leading causes of adult disability worldwide,with neovascularization is crucial for brain repair after stroke.However,neutrophil infiltration hinders effective neovascularization,necessitating timely clearance by microglia through phagocytosis.Unfortunately,microglial phagocytic function is often impaired by metabolic defects,hindering post-stroke recovery.Ginsenoside Rg1,derived from Panax ginseng,exhibits neuroprotective properties and regulates cellular metabolism in vitro but its therapeutic application is limited by poor brain penetration.Here,we present a targeted delivery system utilizing neutrophil-like cell membrane vesicles(NCM),prepared via nitrogen cavitation,to enhance Rg1 delivery to the brain.These bio-mimetic vesicles exploit the inherent targeting ability of neutrophil membranes to reach brain injury sites and are subsequently taken up by microglia.Our findings demonstrate that Rg1-loaded vesicles enhance microglial clearance of neutrophils,reduce neutrophil extracellular traps release,and mitigate tissue damage.These effects improve the post-stroke microenvironment,promote vascular remodeling,and ultimately contribute to func-tional recovery.This strategy highlights the potential of targeted reprogramming microglial cells to enhance their endogenous repair capabilities,offering a promising therapeutic avenue for ischemic stroke management.展开更多
Plant-derived nanovesicles(PDNVs),including plant extracellular vesicles(EVs)and plant exosome-like nanovesicles(ELNs),are natural nano-sized membranous vesicles containing bioactive molecules.PDNVs consist of a bilay...Plant-derived nanovesicles(PDNVs),including plant extracellular vesicles(EVs)and plant exosome-like nanovesicles(ELNs),are natural nano-sized membranous vesicles containing bioactive molecules.PDNVs consist of a bilayer of lipids that can effectively encapsulate hydrophilic and lipophilic drugs,improving drug stability and solubility as well as providing increased bioavailability,reduced systemic toxicity,and enhanced target accumulation.Bioengineering strategies can also be exploited to modify the PDNVs to achieve precise targeting,controlled drug release,and massive production.Meanwhile,they are capable of crossing the blood-brain barrier(BBB)to transport the cargo to the lesion sites without harboring human pathogens,making them excellent therapeutic agents and drug delivery nanoplatform candidates for brain diseases.Herein,this article provides an initial exposition on the fundamental characteristics of PDNVs,including biogenesis,uptake process,isolation,purification,characterization methods,and source.Additionally,it sheds light on the investigation of PDNVs’utilization in brain diseases while also presenting novel perspectives on the obstacles and clinical advancements associated with PDNVs.展开更多
基金supported by National Natural Science Foundation of China (U22A20383)Natural Science Foundation of Zhejiang Province (LY24H300001)+2 种基金Fundamental Research Funds for the Central Universities (226-2022-00125)Zhejiang Province Postdoctoral Research Excellence Funding Project (ZJ2023151)Pharmacy 80 Basic Research Funding in College of Pharmaceutical Sciences, Zhejiang University Education Foundation。
文摘Asthma, one of the most prevalent chronic inflammatory diseases, remains challenging to manage effectively. Current therapies commonly alleviate symptoms through broad immunosuppression and bronchodilation but fail to target disease-specific molecular pathways. Genetic intervention using small interfering RNA(siRNA) has emerged as a promising strategy for asthma therapy. However, its success is largely hindered by the lack of an efficient delivery approach targeting airway epithelial cells(AECs). Here, we developed a novel inhalable siRNA delivery system based on artificially prepared nanovesicles through designed extrusion processes of mesenchymal stem cells. To enable an effective inhalation delivery of siRNA via nanovesicles, various parameters, including extrusion cycles,membrane pore sizes, and centrifugal forces were examined through orthogonal testing.Results revealed that the artificially prepared nanovesicles demonstrated remarkable capability to deliver thymic stromal lymphopoietin-targeted siRNA into AECs and substantially suppressed the inflammatory pathways and goblet cell hyperplasia, and eventually achieved a significant inhibition of asthma symptoms in ovalbumin-induced asthma models. Thus, the present study provides a novel nebulized nanovesicle-based carrier for effective delivery of siRNA through local inhalation, offering a promising therapeutic delivery platform for asthma and potentially other respiratory diseases.
基金supported by the National Natural Science Foundation of China(No.NSFC31872754)。
文摘Established evidence has unveiled two strategies for treating cancer:depleting tumor-associated macrophages(TAMs)and reprogramming M2-like TAMs into an antitumor M1 phenotype.Here,we designed novel p H-sensitive biomimetic hybrid nanovesicles(EDHPA)loaded with doxorubicin(DOX).DOX@EDHPA can specifically target TAMs by activating macrophage-derived exosomes(M1-Exos)and anisamide(AA)as cancer-specific targeting ligands.In vitro and in vivo studies demonstrated that DOX@EDHPA could efficiently be delivered to the tumor site and taken up by cells.Meanwhile,it synergistically enhanced immunogenic cell death(ICD)and induced a subsequent antigen-specific T cell immune response.The tumor inhibitory rate of the DOX@EDHPA group was 1.42 times that of the free DOX group.Further analysis showed that the excellent antitumor effects of DOX@EDHPA should ascribe to the homing effect of M1-Exos on macrophages and the repolarization to antitumor M1 TAMs,which induced the elevated secretion of pro-infiammatory factors.Therefore,the hybrid EDHPA targeting TAMs to reshape the tumor microenvironment constituted a novel immunochemotherapy strategy to inhibit tumor growth.
基金supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (project number RS-2024-00340542)supported in part (to B.J.S.) by the Intramural Fund of National Institute of Alcohol Abuse and Alcoholismsupported by the 2022 research grant from the Korean Society of Ginseng
文摘Metabolic dysfunction-associated fatty liver disease(MASLD)and alcohol-associated liver disease(ALD)are prevalent chronic liver diseases that can progress to steatohepatitis,fibrosis,cirrhosis,and ultimately liver failure.Here,we demonstrated that oral administration of GNVs provided substantial protection against liver injury and fibrosis in MASLD and ALD mouse models.In a Western-style high-fat diet-induced MASLD model and a chronic binge alcohol-induced ALD model,GNVs treatment significantly reduced gut leakiness by restoring intestinal junctional complex proteins and rebalancing the gut microbiome.GNVs attenuated hepatic lipid accumulation,oxidative stress and fibrogenicmarkers.GNV treatment downregulated the fibrosis-associated tissue inhibitor of metalloproteinase-2(TIMP2)pathway in hepatic stellate cells,which is linked to enhanced matrix degradation and reduced fibrogenesis.GNVs prevent MASLD-and ALD-associated gut barrier dysfunction and liver fibrosis through modulation of the gut-liver axis and the TIMP2 pathway.Edible GNVs represent a novel,multifaceted therapeutic strategy for managing chronic liver diseases.
基金supported by the Science and Technology Program of Tianjin in China(Grant No.:23ZYJDSS00030).
文摘Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost,sustainability,and tissue targeting.Thus,they hold promise for disease treatment and drug delivery.In this study,we proposed a time-efficient method,PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles(GDNVs).Subsequently,curcumin(CUR)was loaded onto GDNV by ultrasonic incubation.The optimum conditions for ginger-derived nanovesicles loaded with curcumin(CG)were ultrasound time of 3 min,a carrier-to-drug ratio(GDNV:CUR)of 1:1.The study achieved a high loading capacity(94.027%±0.094%)and encapsulation efficiency(89.300%±0.344%).Finally,the drugs'in vivo distribution and anti-colitis activity were investigated in mice.CG was primarily distributed in the colon after oral administration.Compared to CUR and GDNV,CG was superior in improving disease activity,colon length,liver and spleen coefficients,myeloperoxidase activity,and biochemical factor levels in ulcerative colitis(UC)mice.In addition,CG plays a protective role against UC by modulating serum metabolite levels and gut flora.In summary,our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.
文摘AIM:To investigate the preparation,physicochemical characterization and cytotoxicity in vitro of Gemcitabine-loaded poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-PDLLA) nanovesicles. METHODS:The nanovesicle carriers were prepared from the amphiphilic block copolymer of PEG-PDLLA by a double emulsion technique,and gemcitabine was used as the model drug. The morphology of the nanovesicles was determined by scanning and transmission electron microscopy,and the drug content,drug entrapment and drug-release curve in vitro were detected by UV-Vis-NIR spectrophotometry. Cytotoxicity in the human pancreatic cancer cell line SW1990 was tested by 3-(4,5-dimethyl) ethiazole (MTT) assay.RESULTS:The gemcitabine-loaded nanovesicles were hollow nanospheres with a mean size of 200.6 nm,drugloading of 4.14% and drug embedding ratio of 20.54%. The nanovesicles showed excellent controlled release that was characterized by a fast initial release during the first 72 h,followed by a slower and continuous release. The MTT assay demonstrated that gemcitabine-loaded nanovesicles exhibited dose-dependent and time-delayed cytotoxicity in the human pancreatic cancer cell line SW1990.CONCLUSION:Gemcitabine-loaded PEG-PDLLA nanovesicles prepared by a double emulsion technique exhibited good performance for controlled drug release,and had similar cytotoxic activity to free gem-citabine.
基金financially supported by the National Natural Science Foundation of China (Nos.31771036,51703132)the Basic Research Program of Shenzhen (Nos.JCYJ20180507182413022,JCYJ20170412111100742)the Guangdong Province Natural Science Foundation of Major Basic Research and Cultivation Project (No.2018B030308003)。
文摘Gold nanovesicles(GVs) with unique plasmonic property and large cavity hold great potential as a stimuli-responsive nanocarrier to deliver drugs for efficient tumor chemotherapy and other therapies synergistically.Herein,we developed doxorubicin-loaded gold nanovesicles(DGVs),offering infrared thermal(IRT) and photoacoustic(PA) dual-modal imaging guided mild hype rthermia-enhanced chemophotothermal cancer synergistic therapy.The DGVs are self-assembled by gold nanoparticles modified with amphiphilic copolymer in a predetermined concentration of doxorubicin through film rehydration method.Under the influence of laser excitation,the as-prepared DGVs exhibited good photothermal effect,which triggered the structural disruption of GVs and thus,allowed the efficient release of encapsulated DOX to enhance cell uptake for fluorescence imaging and tumor chemotherapy,respectively.In addition,DGVs also showed a strong PA and IRT signals in vivo.Our study demonstrated the potential of DGVs as stimuli-responsive drug delivery systems and cancer theranostics.
文摘Squamous cell carcinoma (SCC) and melanoma are malignant human cancers of the skin with an annual mortality that exceeds 10,000 cases every year in the USA alone. In this study, the lysosomal protein saposin C (SapC) and the phospholipid dioloylphosphatidylserine (DOPS) were assembled into cancer-selective nanovesicles (SapC-DOPS) and successfully tested using several in vitro and in vivo skin cancer models. Using MTT assay that measures the percentage of cell death, SapC-DOPS cytotoxic effect on three skin tumor cell lines (squamous cell carcinoma, SK-MEL-28, and MeWo) was compared to two normal nontumorigenic skin cells lines, normal immortalized keratinocyte (NIK) and human fibroblast cell (HFC). We observed that the nanovesicles selectively killed the skin cancer cells by inducing apoptotic cell death whereas untransformed skin cancer cells remained unaffected. Using subcutaneous skin tumor xenografts, animals treated with SapC-DOPS by subcutaneous injection showed a 79.4% by volume tumor reduced compared to the control after 4 days of treatment. We observed that the nanovesicles killed skin cancer cells by inducing apoptotic cell death compared to the control as revealed by TUNEL staining of xenograft tumor sections.
基金supported by the Tianjin Committee of Science and Technology of China(No.21ZYJDJC00080 and No.22ZYJDSS00040).
文摘Herbal medicine(HM)has been extensively researched and widely used since ancient times.Currently,as one of the emerging directions in HM modernization research,herbal medicine-derived nanovesicles(HMDNV),a type of nanoparticle obtained from destructed plant tissues,hold considerable promise for disease treatment and drug delivery.The recent studies related to HMDNV and miRNAs are summarized in this review,with a special emphasis on their basic characteristics and biological activities,to provide ideas for future scientific research on HMDNV and enrich the content of active components of Traditional Chinese Medicine(TCM).
基金financially supported by the National Key Research and Development Program of China (No.2021YFA1201200)the National Natural Science Foundation of China (Nos. 51833008, 52173141 and 82102192)+1 种基金Zhejiang Provincial Key Research and Development Program (No.2020C01123)China Postdoctoral Science Foundation (No.2019M662059)
文摘Oligonucleotide therapeutics have great potential to target the currently undruggable genes and to generate entirely new therapeutic paradigms in multiple types of disease,thus having attracted much attention in recent years.However,their applications are greatly hindered by a lack of safe and efficient oligonucleotide-delivery vectors.Polyplex nanovesicles formed from oligonucleotides and the cationic block have shown exceptional features for the delivery of therapeutic oligonucleotides and other biopharmaceuticals.Nevertheless,these polyplex nanovesicles are deeply fraught with difficulty in tolerating physiological ionic strength.Inspired by the high binding ability between the dipicolylamine(DPA)/zinc(Ⅱ)complex and the phosphodiester moieties of oligonucleotides,herein,we designed a coordinative cationic block to solve the intrinsic stability dilemma.Moreover,we found the stability of the resulted polyplex nanovesicles could be easily tuned by the content of coordinated zinc ions.In vitro cellular studies implied that the prepared zinc(Ⅱ)-coordinative polyplex nanovesicles preferred to retain in the lysosomes upon internalization,making them ideal delivery candidates for the lysosome-targeting oligonucleotide therapeutics.
文摘Lipidic nanovesicles (so called liposomes) were one the earliest forms of nanovectors. One of their limits was our lack of knowledge on the delivery pathway of their content to the target cell cytoplasm. The present communication describes an efficient way to enhance the delivery. Pulsed electric fields (PEF) are known since the early 80’s to mediate a fusogenic state of plasma membranes when applied to a cell suspension or a tissue. Polykaryons are detected when PEF are applied on cells in contact during or after the pulses. Heterofusion can be obtained when a cell mixture is pulsed. When lipidic nanovesicles, either small unilamellar vesicles (SUVs) or large unilamellar vesicles (LUVs), are electrostatically brought in contact with electropermeabilized cells by a salt bridge, their content is delivered into the cytoplasm in electropermeabilized cells. The PEF parameters are selected to affect specifically the cells leaving the vesicles unaffected. It is the electropermeabilized state of the cell membrane that is the trigger of the merging between the plasma membrane and the lipid bilayer. The present investigation shows that the transfer of macromolecules can be obtained;i.e. 20 kD dextrans can be easily transferred while a direct transfer does not take place under the same electrical parameters. Cell viability was not affected by the treatment. As delivery is present only on electropermeabilized cells, a targeting of the effect is obtained in the volume where the PEF parameters are over the critical value for electropermeabilization. A homogeneous cytoplasm labeling is observed under digitised videomicroscopy. The process is a content and “membrane” mixing, following neither a kiss and run or an endocytotic pathway.
文摘Extracellular vesicles(EVs)are naturally occurring,phospholipid bilayer-enclosed vesicles that offer high bioavailability and minimal invasiveness,making them promising candidates for disease treatment,drug delivery vectors,and effective biomarkers for disease detection and diagnosis.As researchers continue to discover and characterize EVs from various origins and biogenesis,their role in intercellular communication for diagnostic and therapeutic purposes becomes increasingly clear.Plant-derived exosome-like nanovesicles(PELNs)are of particular interest due to their compatibility,low toxicity,high bioavailability,ease of absorption,and inherent therapeutic activities.Among the diverse plant sources,lemons stand out for their high nutritional value and wealth of phytochemicals and bioactive components.Recently,there has been significant research into PELNs,focusing on their pharmacological properties and potential applications in drug delivery.This review centres on lemon-derived exosome-like nanovesicles(LELNs),exploring their extraction methods,biological and therapeutic potential,and applications as effective drug delivery systems.By highlighting these aspects,we aim to encourage further research into LELNs to uncover additional properties and potential biomedical applications.
基金supported by National Natural Science Foundation of China(Nos.82104445 and 82470182]Basic Scientific Research Funds of Department of Education of Zhejiang Province(No.KYZD2024013)+2 种基金The Startup Foundation of Zhejiang Provincial People’s Hospital(Nos.C-2023-QDJJ12 and C-2024-ZZJJ05)Science and Technology Plan Project of Traditional Chinese Medicine in Zhejiang Province(No.2025ZR007)The National Administration of Traditional Chinese Medicine(No.GZY-ZJ-KJ-24044).
文摘Myelosuppression is a common and severe side effect of cancer chemotherapy,with current treatments hindered by limitations such as depletion of hematopoietic reserves,poor patient compliance,delayed therapeutic onset,and high cost.To overcome these challenges,we developed Epimedium-derived nanovesicles(ENVs)from the traditional Chinese medicinal herb Epimedium,addressing the solubility and bioavailability issues associated with conventional extracts.ENVs encapsulate bioactive constituents,including icariin and hematopoiesis-promoting ceramides.In a cyclophosphamide(CTX)-induced myelosuppression mouse model,prophylactic and therapeutic oral administration of ENVs effectively alleviated hematopoietic suppression,significantly outperforming the Epimedium-based herbal extract“Joungal”(Shengbai Formula)despite equivalent icariin content.Notably,ENVs promoted hematopoietic stem cell(HSC)proliferation—an outcome rarely achieved with existing therapies.Mechanistically,ENVs modulated the gut microbiota,enriching lactobacillus species and enhancing lactate production.This microbiota-driven lactate signaling stimulated LepR+mesenchymal stem cells(MSCs)in the bone marrow niche to secrete stromal cellderived factor-1(SDF-1)and stem cell factor(SCF),thereby supporting HSC expansion and restoring hematopoietic function.In vivo safety evaluations confirmed the excellent biocompatibility of ENVs.Our findings uncover a gut-lactate-bone marrow axis through which ENVs enhance hematopoiesis and promote HSC regeneration.This work introduces a cost-effective,scalable,and orally administrable biomaterial platform with strong translational potential for the prevention and treatment of chemotherapy-induced myelosuppression.
基金Supported by Provincial Key R&D Program Project of Zhejiang Provincial Science and Technology Department(No.2019C03024)。
文摘Objective:To explore the potential of honeysuckle-derived exosome-like nanovesicles(HELNVs)for preventing cisplatin-induced acute kidney injury(AKI).Methods:The renoprotective efficacy of HELNVs against cisplatin-induced AKI was assessed in human kidney cell-2(HK-2)cells exposed to 100μmol/L cisplatin for 24 h,followed by HELNVs(50-200μg/mL)for another 24 h;the optimal therapeutic concentration was determined as 100μg/mL.At this concentration,oxygen species(ROS)levels were measured by flow cytometry.Male C57BL/6 mice received a single intraperitoneal injection of cisplatin(30 mg/kg)to establish an AKI model and were then computer-randomized into 3 groups(n=6 per group):control group,daily intraperitoneal administration of normal saline(0.9%NaCl);the cisplatin-injured group,same NaCl regimen;the HELNVs treatment group,daily intraperitoneal administration of HELNVs(30 mg/kg)for 5 consecutive days,with euthanasia on day 6.Renal accumulation of HELNVs was tracked by small-animal multispectral imaging(peak uptakee at 8-10h).Functional assessment included serum creatinine and blood urea nitrogen(BUN)quantified with an automated biochemical analyzer.Molecular analyses included enzyme-linked immunosorbent assay(ELISA)quantification of interleukin(IL)-1β,IL-6,IL-10,and tumor necrosis factor-α(TNF-α).Results:HELNVs significantly reduced ROS,inflammatory responses,and apoptosis in cisplatin-treated HK-2 cells(P<0.01).In cisplatin-induced AKI mice,HELNVs were efficiently absorbed by kidney cells,effectively prevented oxidative damage and mitochondrial dysfunction(P<0.01).Following treatment with 30 mg/kg HELNVs,serum creatinine and BUN levels were markedly reduced(P<0.01).ELISA results showed decreased levels of IL-1β,IL-6,and TNF-α,along with up-regulated IL-10(P<0.01).Conclusion:HELNVs may serve as a promising therapeutic approach for ameliorating cisplatininduced AKI,offering a potential novel treatment option for managing this condition in clinical settings.
基金the Director CSIR-CFTRI for facilities and supportsupported by Grant-in-aid extramural project received from DST-Science and Engineering Board,New Delhi,India(Grant no:CRG/2023/001282)the Department of Biotechnology,GoI,(BT/PR26926/NNT/28/1500/2017)for the equipment(SEM)support.
文摘Human appetite is tightly regulated by Ghrelin(GHRL),a 28aa peptide hormone.In an empty stomach,GHRL is secreted by the stomach epithelial glandular cells which acts on the hypothalamus,leading to appetite stimulation and food intake.Loss of appetite,known as anorexia is a debilitating problem in patients undergoing chemotherapy as well as soldiers working at high altitudes(HA),primarily caused by lower plasma GHRL.Though restoration of plasma GHRL may re-establish appetite,naked GHRL delivery via enteral route is not possible due to its degradation in the gastrointestinal(GI)tract while parenteral route administration is discouraged due to its low plasma half-life.Plant-derived nanovesicles(PDNVs)are exosome-mimetic vesicles naturally present in plants.PDNVs are emerging as natural nanocarriers for the delivery of distinct cargoes for both in vitro and in vivo applications.Cardamom seeds are a nutraceutical spice with known appetite-stimulating attributes.Herein,we encapsulated GHRL peptide in small cardamom-derived PDNVs(SCDNVs)by active sonication and evaluated its in vitro bioavailability and gastrointestinal stability.SCDNVs exhibited high encapsulation efficiency for GHRL and were non-toxic to Caco-2 cells.Compared to native GHRL,SCDNVencapsulated GHRL displayed better intracellular delivery potential in Caco2 cells and was resistance to the simulated gastrointestinal digestion process in vitro.Further,SCDNVs also possessed appetite-stimulating phytochemicals such asα-terpinyl acetate andα-terpinol.Hence,GHRL-encapsulated SCDNVs represent a synergistic cocktail of an appetite-inducing hormone and phytochemicals in bioavailable form for anorexia therapy.
基金upported by the following funds:National Natural Science Foundation of China(No.82172568 and 82404561)Liaoning Province Applied Basic Research Program(No.2025JH2/101330178)+2 种基金the Postdoctoral Fellowship Program(Grade B)of China Postdoctoral Science Foundation(GZB20240179)the China Postdoctoral Science Foundation(No.2025M773915)Prospective Basic Research Project of 2024 Scientific Research Project of Liaoning Department of Education(LJ212410163042,China).
文摘Membrane-derived biomimetic nanovesicles have emerged as a promising platform in cancer immunotherapy due to their intrinsic biocompatibility,functional plasticity,and capability to modulate immune responses.By integrating various immunotherapeutic agents,including immune checkpoint inhibitors,tumor antigens,and immunostimulatory adjuvants,these vesicles can be engineered to mimic natural immune communication and overcome key barriers in the tumor immune microenvironment.This review summarizes recent advances in the design,functionalization,and application of biomimetic nanovesicles for anti-tumor immunity.We particularly highlight strategies that harness these vesicles to enhance innate and adaptive immune responses,reverse immune suppression,and synergize with existing immunotherapy modalities.Furthermore,we discuss the challenges associated with biosafety,large-scale manufacturing,and clinical translation.Continued innovation in vesicle engineering and immunological modulation will be crucial for transforming biomimetic nanovesicles into viable next-generation cancer immunotherapeutics.
基金supported by grants from National Natural Science Foundation of China(32301975)Shenzhen Medical Research Funds(A2303058)+2 种基金Shenzhen Science and Technology Program(ZDSYS20220117155800001)Natural Science Foundation of Guangdong Province(2022A1515010303)China Postdoctoral Science Foundation(2024T170581).
文摘Alcoholic liver disease(ALD)is a common chronic liver disease worldwide that urgently needs safe and effective strategies.Clams are popular seafood with hepatoprotective effects,while the effective components and mechanisms remain unclear.Herein,we demonstrated that clam-derived exosome-like nanovesicles(CENs)ameliorated alcohol-induced liver injury by preventing mitochondrial dysfunction and inhibiting mitochondrial apoptotic pathway.Results showed that CENs exhibited exosome-like morphology with a particle size of 120.08±1.60 nm.Mass spectrometry revealed that CENs naturally carry multiple functional lipids and proteins.Furthermore,CENs were found to survive in the gastrointestinal environment and accumulate in the liver of mice following oral administration.Importantly,administration of CENs effectively alleviated alcohol-induced liver injury and hepatocyte death in mice by restoring mitochondrial function,as indicated by increased ATP levels,enhanced mitochondrial complex I activity,and reduced mitochondrial ROS production.Further cell experiments indicated that CENs could be phagocytosed by HepG2 cells and effectively alleviated alcohol-induced hepatocyte apoptosis by inhibiting mitochondrial apoptotic pathway.Collectively,these results indicate that CENs possess potent hepatoprotective properties and may serve as a novel functional ingredient for managing alcoholic liver disease.
基金supported by grants from the National Natural Science Foundation of China(32322045 to Z.Li,22207050 to L.Li,32301162 to F.Wang)Dongguan Science and Technology of Social Development Program(20231800925372 to Z.Li,20231800912372 to F.Wang).
文摘Exosomes are natural nano-size particles secreted by human cells,containing numerous bioactive cargos.Serving as crucial mediators of intercellular communication,exosomes are involved in many physiological and pathological processes,such as inflammation,tissue injury,cardiovascular diseases,tumorigenesis and tumor development.Exosomes have exhibited promising results in the diagnosis and treatment of cancer,cardiovascular diseases and others.They are a rapidly growing class of drug delivery vehicles with many advantages over conventional synthetic carriers.Exosomes used in therapeutic applications encounter several challenges,such as the lack of tissue targeting capabilities and short residence time.In this review,we discuss recent advances in exosome engineering to improve tissue targeting and describe the current types of engineered exosome-like nanovesicles,and summarize their preclinical applications in the treatment of diseases.Further,we also highlight the latest engineering strategies developed to extend exosomes retention time in vivo and exosome-like nanovesicles.
基金supported by the National Natural Science Foundation(NSFC-STINT 82311530116)the Sichuan Science and Technology Program(2025ZNSFSC0682)+1 种基金the 111 Project(B18035)the National Natural Science Foundation(82173761).
文摘Dysregulated autophagy is a hallmark of Alzheimer’s disease(AD),yet the extent of impairment in macroautophagy and chaperonemediated autophagy(CMA)remains unclear.Here,we show that both pathways are disrupted in AD model mice,precedingβ-amyloid accumulation and driving disease progression.However,therapeutic autophagy modulation is severely restricted by the blood–brain barrier(BBB).To overcome this,we developed Microglia-Liposome Fusion Extrusion(MiLi-FE),a method to engineer microglia-derived nanovesicles(AR@ENV)for the codelivery of AR7(a CMA inducer)and rapamycin(a macroautophagy inducer).Leveraging its microglial membrane origin,AR@ENV effectively crosses the BBB and targets inflammatory sites in the AD brain,where it is internalized by neurons.Once inside,they synchronously activate both autophagy pathways:AR7 antagonizes retinoic acid receptor alpha(RARα)to enhance CMA,while rapamycin inhibits mTOR to promote macroautophagy.This coordinated activation enhances clearance ofβ-amyloid and other toxic aggregates,restores proteostasis,and provides robust neuroprotection.Furthermore,the strategy ameliorates neuroinflammation and significantly rescues cognitive deficits in two distinct AD mouse models.By integrating synchronized dual autophagy activation with targeted biomimetic delivery,AR@ENV represents a promising therapeutic candidate for AD.Moreover,the MiLi-FE platform offers a versatile and scalable approach for delivering diverse therapeutics to the central nervous system,extending its potential applicability to a range of neurological disorders.
基金supported by the National Natural Science Founda-tion of China(U2202214,82074044,82374060,U21A20410)the Na-tional Key R&D Program of China(2022YFC3500300)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-020).
文摘Stroke remains one of the leading causes of adult disability worldwide,with neovascularization is crucial for brain repair after stroke.However,neutrophil infiltration hinders effective neovascularization,necessitating timely clearance by microglia through phagocytosis.Unfortunately,microglial phagocytic function is often impaired by metabolic defects,hindering post-stroke recovery.Ginsenoside Rg1,derived from Panax ginseng,exhibits neuroprotective properties and regulates cellular metabolism in vitro but its therapeutic application is limited by poor brain penetration.Here,we present a targeted delivery system utilizing neutrophil-like cell membrane vesicles(NCM),prepared via nitrogen cavitation,to enhance Rg1 delivery to the brain.These bio-mimetic vesicles exploit the inherent targeting ability of neutrophil membranes to reach brain injury sites and are subsequently taken up by microglia.Our findings demonstrate that Rg1-loaded vesicles enhance microglial clearance of neutrophils,reduce neutrophil extracellular traps release,and mitigate tissue damage.These effects improve the post-stroke microenvironment,promote vascular remodeling,and ultimately contribute to func-tional recovery.This strategy highlights the potential of targeted reprogramming microglial cells to enhance their endogenous repair capabilities,offering a promising therapeutic avenue for ischemic stroke management.
基金the National Natural Science Foundation of China(82125037,82274104,82074024,82374042)National Key R&D Program of China(2023YFC2308200)+3 种基金Jiangsu Provincial Medical Innovation Center(CXZX202225)the Natural Science Foundation of Jiangsu Province(BK20240144)the Innovation Projects of State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture(NZYSKL240103)Nanjing University of Chinese Medicine’s Project(RC202407).
文摘Plant-derived nanovesicles(PDNVs),including plant extracellular vesicles(EVs)and plant exosome-like nanovesicles(ELNs),are natural nano-sized membranous vesicles containing bioactive molecules.PDNVs consist of a bilayer of lipids that can effectively encapsulate hydrophilic and lipophilic drugs,improving drug stability and solubility as well as providing increased bioavailability,reduced systemic toxicity,and enhanced target accumulation.Bioengineering strategies can also be exploited to modify the PDNVs to achieve precise targeting,controlled drug release,and massive production.Meanwhile,they are capable of crossing the blood-brain barrier(BBB)to transport the cargo to the lesion sites without harboring human pathogens,making them excellent therapeutic agents and drug delivery nanoplatform candidates for brain diseases.Herein,this article provides an initial exposition on the fundamental characteristics of PDNVs,including biogenesis,uptake process,isolation,purification,characterization methods,and source.Additionally,it sheds light on the investigation of PDNVs’utilization in brain diseases while also presenting novel perspectives on the obstacles and clinical advancements associated with PDNVs.
