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
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
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
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
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
Acute lung injury(ALI)is a devastating inflammatory disease.MicroRNA155(miR155)in alveolar macrophages and lung epithelial cells enhances inflammatory reactions by inhibiting the suppressor of cytokine signaling 1(SOC...Acute lung injury(ALI)is a devastating inflammatory disease.MicroRNA155(miR155)in alveolar macrophages and lung epithelial cells enhances inflammatory reactions by inhibiting the suppressor of cytokine signaling 1(SOCS1)in ALI.Anti-miR155 oligonucleotide(AMO155)have been suggested as a potential therapeutic reagent for ALI.However,a safe and efficient carrier is required for delivery of AMO155 into the lungs for ALI therapy.In this study,cell membrane-derived nanovesicles(CMNVs)were produced from cell membranes of LA4 mouse lung epithelial cells and evaluated as a carrier of AMO155 into the lungs.For preparation of CMNVs,cell membranes were isolated from LA4 cells and CMNVs were produced by extrusion.Cholesterol-conjugated AMO155(AMO155c)was loaded into CMNVs and extracellular vesicles(EVs)by sonication.The physical characterization indicated that CMNVs with AMO155c(AMO155c/CMNV)were membrane-structured vesicles with a size of�120nm.The delivery efficiency and therapeutic efficacy of CMNVs were compared with those of EVs or polyethylenimine(25kDa,PEI25k).The delivery efficiency of AMO155c by CMNVs was similar to that by EVs.As a result,the miR155 levels were reduced by AMO155c/CMNV and AMO155c/EV.AMO155c/CMNV were administered intratracheally into the ALI models.The SOCS1 levels were increased more efficiently by AMO155c/CMNV than by the others,suggesting that miR155 effectively was inhibited by AMO155c/CMNV.In addition,the inflammatory cytokines were reduced more effectively by AMO155c/CMNV than they were by AMO155c/EV and AMO155c/PEI25k,reducing inflammation reactions.The results suggest that CMNVs are a useful carrier of AMO155c in the treatment of ALI.展开更多
Although various anti-osteoporosis drugs are available,the limitations of these therapies,including drug resistance and collateral responses,require the development of novel anti-osteoporosis agents.Rhizoma Drynariae ...Although various anti-osteoporosis drugs are available,the limitations of these therapies,including drug resistance and collateral responses,require the development of novel anti-osteoporosis agents.Rhizoma Drynariae displays a promising anti-osteoporosis effect,while the effective component and mechanism remain unclear.Here,we revealed the therapeutic potential of Rhizoma Drynariae-derived nanovesicles(RDNVs)for postmenopausal osteoporosis and demonstrated that RDNVs potentiated osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)by targeting estrogen receptor-alpha(ERα).RDNVs,a natural product isolated from fresh Rhizoma Drynariae root juice by differential ultracentrifugation,exhibited potent bone tissue-targeting activity and anti-osteoporosis efficacy in an ovariectomized mouse model.RDNVs,effectively internalized by hBMSCs,enhanced proliferation and ERαexpression levels of hBMSC,and promoted osteogenic differentiation and bone formation.Mechanistically,via the ERαsignaling pathway,RDNVs facilitated mRNA and protein expression of bone morphogenetic protein 2 and runt-related transcription factor 2 in hBMSCs,which are involved in regulating osteogenic differentiation.Further analysis revealed that naringin,existing in RDNVs,was the active component targeting ERαin the osteogenic effect.Taken together,our study identified that naringin in RDNVs displays exciting bone tissue-targeting activity to reverse osteoporosis by promoting hBMSCs proliferation and osteogenic differentiation through estrogen-like effects.展开更多
Androgenic alopecia(AGA)is a highly prevalent form of non-scarring alopecia but lacks effective treatments.Stem cell exosomes have similar repair effects to stem cells,suffer from the drawbacks of high cost and low yi...Androgenic alopecia(AGA)is a highly prevalent form of non-scarring alopecia but lacks effective treatments.Stem cell exosomes have similar repair effects to stem cells,suffer from the drawbacks of high cost and low yield yet.Cell-derived nanovesicles acquired through mechanical extrusion exhibit favorable biomimetic properties similar to exosomes,enabling them to efficiently encapsulate substantial quantities of therapeutic proteins.In this study,we observed that JAM-A,an adhesion protein,resulted in a significantly increased the adhesion and resilience of dermal papilla cells to form snap structures against damage caused by dihydrotestosterone and macrophages,thereby facilitating the process of hair regrowth in cases of AGA.Consequently,adipose-derived stem cells were modified to overexpress JAM-A to produce engineered JAM-A overexpressing nanovesicles(JAM-A^(OE)@NV).The incorporation of JAM-A^(OE)@NV into a thermosensitive hydrogel matrix(JAM-A^(OE)@NV Gel)to effectively addresses the limitations associated with the short half-life of JAM-A^(OE)@NV,and resulted in the achievement of a sustained-release profile for JAM-A^(OE)@NV.The physicochemical characteristics of the JAM-A^(OE)@NV Gel were analyzed and assessed for its efficacy in promoting hair regrowth in vivo and vitro.The JAM-A^(OE)@NV Gel,thus,presents a novel therapeutic approach and theoretical framework for promoting the treatment of low cell adhesion diseases similar to AGA.展开更多
Plant-derived nanovesicles(PDNVs)derived from natural green products have emerged as an attractive nanoplatform in biomedical application.They are usually characterized by unique structural and biological functions,su...Plant-derived nanovesicles(PDNVs)derived from natural green products have emerged as an attractive nanoplatform in biomedical application.They are usually characterized by unique structural and biological functions,such as the bioactive lipids/proteins/nucleic acids as therapeutics and targeting groups,immune-modulation,and long-term circulation.With the rapid development of nanotechnology,materials,and synthetic chemistry,PDNVs can be engineered with multiple functions for efficient drug delivery and specific killing of diseased cells,which represent an innovative biomaterial with high biocompatibility for fighting against cancer.In this review,we provide an overview of the state-of-theart studies concerning the development of PDNVs for cancer therapy.The original sources,methods for obtaining PDNVs,composition and structure are introduced systematically.With an emphasis on the featured application,the inherent anticancer properties of PDNVs as well as the strategies in constructing multifunctional PDNVs-based nanomaterials will be discussed in detail.Finally,some scientific issues and technical challenges of PDNVs as promising options in improving anticancer therapy will be discussed,which are expected to promote the further development of PDNVs in clinical translation.展开更多
Parkinson’s disease(PD)is one of the most prevalent neurodegenerative diseases.It is usually accompanied by motor and non-motor symptoms that seriously threaten the health and the quality of life.Novel medications ar...Parkinson’s disease(PD)is one of the most prevalent neurodegenerative diseases.It is usually accompanied by motor and non-motor symptoms that seriously threaten the health and the quality of life.Novel medications are urgently needed because current pharmaceuticals can relieve symptoms but cannot stop disease progression.The microbiota-gut-brain axis(MGBA)is closely associated with the occurrence and development of PD and is an effective therapeutic target.Tetrahedral framework nucleic acids(tFNAs)can modulate the microbiome and immune regulation.However,such nucleic acid nanostructures are very sensitive to acids which hinder this promising approach.Therefore,we prepared exosome-like nanovesicles(Exo@tac)from ginger that are acid resistant and equipped with tFNAs modified by antimicrobial peptides(AMP).We verified that Exo@tac regulates intestinal bacteria associated with the microbial-gut-brain axis in vitro and significantly improves PD symptoms in vivo when administered orally.Microbiota profiling confirmed that Exo@tac normalizes the intestinal flora composition of mouse models of PD.Our findings present a novel strategy for the development of PD drugs and the innovative delivery of nucleic acid nanomedicines.展开更多
Photosynthetic bacteria(PSB)has shown significant potential as a drug or drug delivery system owing to their photothermal capabilities and antioxidant properties.Nevertheless,the actualization of their potential is im...Photosynthetic bacteria(PSB)has shown significant potential as a drug or drug delivery system owing to their photothermal capabilities and antioxidant properties.Nevertheless,the actualization of their potential is impeded by inherent constraints,including their considerable size,heightened immunogenicity and compromised biosafety.Conquering these obstacles and pursuing more effective solutions remains a top priority.Similar to extracellular vesicles,bacterial outer membrane vesicles(OMVs)have demonstrated a great potential in biomedical applications.OMVs from PSB encapsulate a rich array of bioactive constituents,including proteins,nucleic acids,and lipids inherited from their parent cells.Consequently,they emerge as a promising and practical alternative.Unfortunately,OMVs have suffered from low yield and inconsistent particle sizes.In response,bacteria-derived nanovesicles(BNVs),created through controlled extrusion,adeptly overcome the challenges associated with OMVs.However,the differences,both in composition and subsequent biological effects,between OMVs and BNVs remain enigmatic.In a groundbreaking endeavor,our study meticulously cultivates PSB-derived OMVs and BNVs,dissecting their nuances.Despite minimal differences in morphology and size between PSB-derived OMVs and BNVs,the latter contains a higher concentration of active ingredients and metabolites.Particularly noteworthy is the elevated levels of lysophosphatidylcholine(LPC)found in BNVs,known for its ability to enhance cell proliferation and initiate downstream signaling pathways that promote angiogenesis and epithelialization.Importantly,our results indicate that BNVs can accelerate wound closure more effectively by orchestrating a harmonious balance of cell proliferation and migration within NIH-3T3 cells,while also activating the EGFR/AKT/PI3K pathway.In contrast,OMVs have a pronounced aptitude in anti-cancer efforts,driving macrophages toward the M1 phenotype and promoting the release of inflammatory cytokines.Thus,our findings not only provide a promising methodological framework but also establish a definitive criterion for discerning the optimal application of OMVs and BNVs in addressing a wide range of medical conditions.展开更多
As a high-risk trauma,deep burns are always hindered in their repair process by decreased tissue regeneration capacity and persistent infections.In this study,we developed a simultaneous strategy for deep burn wounds ...As a high-risk trauma,deep burns are always hindered in their repair process by decreased tissue regeneration capacity and persistent infections.In this study,we developed a simultaneous strategy for deep burn wounds treatment using functional nanovesicles with antibacterial and tissue remodeling properties,delivered via a click-chemistry hydrogel.An aggregation-induced emission photosensitizer of 4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1-(2-hydroxyethyl)pyridin-1-ium bromide(THB)with excellent photodynamic properties was first prepared,and then combined with readily accessible adipose stem cells-derived nanovesicles to generate the THB functionalized nanovesicles(THB@ANVs).The THB@ANVs showed strong antibacterial activity against Gram-positive bacteria(up to 100%killing rate),and also beneficial effects on tissue remodeling,including promoting cell migration,cell proliferation,and regulating immunity.In addition,we prepared a click-hydrogel of carboxymethyl chitosan for effective delivery of THB@ANVs on wounds.This hydrogel could be injected to conform to the wound morphology while responding to the acidic microenvironment.In vivo evaluations of wound healing revealed that the THB@ANVs hydrogel dressing efficiently accelerated the healing of second-degree burn wounds by reducing bacterial growth,regulating inflammation,promoting early angiogenesis,and collagen deposition.This study provides a promising candidate of wound dressing with diverse functions for deep burn wound repair.展开更多
Background:Bacterial infections pose a considerable threat to skin wounds,particularly in the case of challenging-to-treat diabetic wounds.Systemic antibiotics often struggle to penetrate deep wound tissues and topica...Background:Bacterial infections pose a considerable threat to skin wounds,particularly in the case of challenging-to-treat diabetic wounds.Systemic antibiotics often struggle to penetrate deep wound tissues and topically applied antibiotics may lead to sensitization,necessitating the development of novel approaches for effectively treating germs in deep wound tissues.Neutrophils,the predominant immune cells in the bloodstream,rapidly release an abundance of molecules via degranulation upon activation,which possess the ability to directly eliminate pathogens.This study was designed to develop novel neutrophil cell engineered nanovesicles(NVs)with high production and explore their bactericidal properties and application in promoting infectious wound healing.Methods:Neutrophils were isolated from peripheral blood and activated in vitro via phorbol myristate acetate(PMA)stimulation.Engineered NVs were prepared by sequentially extruding activated neutrophils followed by ultracentrifugation and were compared with neutrophil-derived exosomes in terms of morphology,size distribution and protein contents.The bactericidal effect of NVs in vitro was evaluated using the spread plate technique,LIVE/DEAD backlight bacteria assay and observation of bacterial morphology.The therapeutic effects of NVs in vivo were evaluated using wound contraction area measurements,histopathological examinations,assessments of inflammatory factors and immunochemical staining.Results:Activated neutrophils stimulated with PMA in vitro promptly release a substantial amount of bactericidal proteins.NVs are similar to exosomes in terms of morphology and particle size,but they exhibit a significantly higher enrichment of bactericidal proteins.In vitro,NVs demonstrated a significant bactericidal effect,presumably mediated by the enrichment of bactericidal proteins such as lysozyme.These NVs significantly accelerated wound healing,leading to a marked reduction in bacterial load,downregulation of inflammatory factors and enhanced collagen deposition in a fullthickness infectious skin defect model.Conclusions:We developed engineered NVs derived from activated neutrophils to serve as a novel debridement method targeting bacteria in deep tissues,ultimately promoting infectious wound healing.展开更多
Natural phytoconstituents exhibit distinct advantages in the management and prevention of inflammatory bowel disease(IBD),attributed to their robust biological activity,multi-target effects,and elevated safety profile...Natural phytoconstituents exhibit distinct advantages in the management and prevention of inflammatory bowel disease(IBD),attributed to their robust biological activity,multi-target effects,and elevated safety profile.Although promising,the clinical application of phytoconstituents have been impeded by poor water solubility,low oral bioavailability,and inadequate colonic targeting.Recent advancements in nanotechnology has offered prospective avenues for the application of phytoconstituents in the treatment of IBD.A common strategy involves encapsulating or conjugating phytoconstituents with nanocarriers to enhance their stability,prolong intestinal retention,and facilitate targeted delivery to colonic inflammatory tissues.Furthermore,drawing inspiration from the self-assembling nanostructures that emerge during the decoction process of Chinese herbs,a variety of natural active compounds-based nanoassemblies have been developed for the treatment of IBD.They exhibit high drug-loading capacities and surmount the challenges posed by poor water solubility and low bioavailability.Notably,phyto-derived nanovesicles,owing to their unique structure and biological functions,can serve as therapeutic agents or novel delivery vehicles for the treatment of IBD.Consequently,this review provides an extensive overview of emerging phytoconstituent-derived nano-medicines/vesicles for the treatment of IBD,intending to offer novel insights for the clinical management of IBD.展开更多
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 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.
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.
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 Basic Science&Engineering Research Program(NRF-2022R1A2B5B01001920)the National Research Foundation,funded by the Ministry of Science and ICT in Korea.
文摘Acute lung injury(ALI)is a devastating inflammatory disease.MicroRNA155(miR155)in alveolar macrophages and lung epithelial cells enhances inflammatory reactions by inhibiting the suppressor of cytokine signaling 1(SOCS1)in ALI.Anti-miR155 oligonucleotide(AMO155)have been suggested as a potential therapeutic reagent for ALI.However,a safe and efficient carrier is required for delivery of AMO155 into the lungs for ALI therapy.In this study,cell membrane-derived nanovesicles(CMNVs)were produced from cell membranes of LA4 mouse lung epithelial cells and evaluated as a carrier of AMO155 into the lungs.For preparation of CMNVs,cell membranes were isolated from LA4 cells and CMNVs were produced by extrusion.Cholesterol-conjugated AMO155(AMO155c)was loaded into CMNVs and extracellular vesicles(EVs)by sonication.The physical characterization indicated that CMNVs with AMO155c(AMO155c/CMNV)were membrane-structured vesicles with a size of�120nm.The delivery efficiency and therapeutic efficacy of CMNVs were compared with those of EVs or polyethylenimine(25kDa,PEI25k).The delivery efficiency of AMO155c by CMNVs was similar to that by EVs.As a result,the miR155 levels were reduced by AMO155c/CMNV and AMO155c/EV.AMO155c/CMNV were administered intratracheally into the ALI models.The SOCS1 levels were increased more efficiently by AMO155c/CMNV than by the others,suggesting that miR155 effectively was inhibited by AMO155c/CMNV.In addition,the inflammatory cytokines were reduced more effectively by AMO155c/CMNV than they were by AMO155c/EV and AMO155c/PEI25k,reducing inflammation reactions.The results suggest that CMNVs are a useful carrier of AMO155c in the treatment of ALI.
基金This work was supported by the National Natural Science Foundation of China(Nos.82174119,81973633 and 82274220)Science and Technology Projects in Liwan District,Guangzhou(Nos.20230710 and 202201009,China)+2 种基金Young Talent Support Project of Guangzhou Association for Science and Technology(No.QT2023036,China)Special focus areas for General Universities in Guangdong Province(No.2022ZDZX2016,China)Guangdong Provincial Administration of Traditional Chinese Medicine Project(No.20233025,China).
文摘Although various anti-osteoporosis drugs are available,the limitations of these therapies,including drug resistance and collateral responses,require the development of novel anti-osteoporosis agents.Rhizoma Drynariae displays a promising anti-osteoporosis effect,while the effective component and mechanism remain unclear.Here,we revealed the therapeutic potential of Rhizoma Drynariae-derived nanovesicles(RDNVs)for postmenopausal osteoporosis and demonstrated that RDNVs potentiated osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)by targeting estrogen receptor-alpha(ERα).RDNVs,a natural product isolated from fresh Rhizoma Drynariae root juice by differential ultracentrifugation,exhibited potent bone tissue-targeting activity and anti-osteoporosis efficacy in an ovariectomized mouse model.RDNVs,effectively internalized by hBMSCs,enhanced proliferation and ERαexpression levels of hBMSC,and promoted osteogenic differentiation and bone formation.Mechanistically,via the ERαsignaling pathway,RDNVs facilitated mRNA and protein expression of bone morphogenetic protein 2 and runt-related transcription factor 2 in hBMSCs,which are involved in regulating osteogenic differentiation.Further analysis revealed that naringin,existing in RDNVs,was the active component targeting ERαin the osteogenic effect.Taken together,our study identified that naringin in RDNVs displays exciting bone tissue-targeting activity to reverse osteoporosis by promoting hBMSCs proliferation and osteogenic differentiation through estrogen-like effects.
基金supported by the Featured Clinical Discipline Project of Shanghai Pudong Fund(Grant No.PWYts2021-07)the East Hospital Affiliated to Tongji University Introduced Talent Research Startup Fund(Grant No.DFRC2019008)the National Natural Science Foundation of China(Grant No.32071186).
文摘Androgenic alopecia(AGA)is a highly prevalent form of non-scarring alopecia but lacks effective treatments.Stem cell exosomes have similar repair effects to stem cells,suffer from the drawbacks of high cost and low yield yet.Cell-derived nanovesicles acquired through mechanical extrusion exhibit favorable biomimetic properties similar to exosomes,enabling them to efficiently encapsulate substantial quantities of therapeutic proteins.In this study,we observed that JAM-A,an adhesion protein,resulted in a significantly increased the adhesion and resilience of dermal papilla cells to form snap structures against damage caused by dihydrotestosterone and macrophages,thereby facilitating the process of hair regrowth in cases of AGA.Consequently,adipose-derived stem cells were modified to overexpress JAM-A to produce engineered JAM-A overexpressing nanovesicles(JAM-A^(OE)@NV).The incorporation of JAM-A^(OE)@NV into a thermosensitive hydrogel matrix(JAM-A^(OE)@NV Gel)to effectively addresses the limitations associated with the short half-life of JAM-A^(OE)@NV,and resulted in the achievement of a sustained-release profile for JAM-A^(OE)@NV.The physicochemical characteristics of the JAM-A^(OE)@NV Gel were analyzed and assessed for its efficacy in promoting hair regrowth in vivo and vitro.The JAM-A^(OE)@NV Gel,thus,presents a novel therapeutic approach and theoretical framework for promoting the treatment of low cell adhesion diseases similar to AGA.
基金This work was supported by the National Natural Science Foundation of China(Nos.81972547 and 82273306)the Hubei Province health and family planning scientific research project(WJ2023Q011,China).
文摘Plant-derived nanovesicles(PDNVs)derived from natural green products have emerged as an attractive nanoplatform in biomedical application.They are usually characterized by unique structural and biological functions,such as the bioactive lipids/proteins/nucleic acids as therapeutics and targeting groups,immune-modulation,and long-term circulation.With the rapid development of nanotechnology,materials,and synthetic chemistry,PDNVs can be engineered with multiple functions for efficient drug delivery and specific killing of diseased cells,which represent an innovative biomaterial with high biocompatibility for fighting against cancer.In this review,we provide an overview of the state-of-theart studies concerning the development of PDNVs for cancer therapy.The original sources,methods for obtaining PDNVs,composition and structure are introduced systematically.With an emphasis on the featured application,the inherent anticancer properties of PDNVs as well as the strategies in constructing multifunctional PDNVs-based nanomaterials will be discussed in detail.Finally,some scientific issues and technical challenges of PDNVs as promising options in improving anticancer therapy will be discussed,which are expected to promote the further development of PDNVs in clinical translation.
基金supported by the National Natural Science Foundation of China(82370929 and 82401144)Sichuan Science and Technology Program(2022NSFSC0002)+3 种基金Sichuan Province Youth Science and Technology Innovation Team(2022JDTD0021)Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD03202302 and RCDWJS2024-1)China Postdoctoral Science Foundation(CPSF)(2024M752238)Postdoctoral Fellowship Program of CPSF(GZC20231787).
文摘Parkinson’s disease(PD)is one of the most prevalent neurodegenerative diseases.It is usually accompanied by motor and non-motor symptoms that seriously threaten the health and the quality of life.Novel medications are urgently needed because current pharmaceuticals can relieve symptoms but cannot stop disease progression.The microbiota-gut-brain axis(MGBA)is closely associated with the occurrence and development of PD and is an effective therapeutic target.Tetrahedral framework nucleic acids(tFNAs)can modulate the microbiome and immune regulation.However,such nucleic acid nanostructures are very sensitive to acids which hinder this promising approach.Therefore,we prepared exosome-like nanovesicles(Exo@tac)from ginger that are acid resistant and equipped with tFNAs modified by antimicrobial peptides(AMP).We verified that Exo@tac regulates intestinal bacteria associated with the microbial-gut-brain axis in vitro and significantly improves PD symptoms in vivo when administered orally.Microbiota profiling confirmed that Exo@tac normalizes the intestinal flora composition of mouse models of PD.Our findings present a novel strategy for the development of PD drugs and the innovative delivery of nucleic acid nanomedicines.
基金supported by the National Natural Science Foundation of China(32322045,32271420,31971304,and 21977024)The Beijing-Tianjin-Hebei Basic Research Cooperation Project(19JCZDJC64100)+5 种基金Cross-Disciplinary Project of Hebei University(DXK201916)One Hundred Talent Project of Hebei Province(E2018100002)National High-End Foreign Expert Recruitment Plan(G2022003007L)Science Fund for Creative Research Groups of Nature Science Foundation of Hebei Province(B2021201038)Natural Science Foundation of Hebei Province(B2023201108)Hebei Province Higher Education Science and Technology Research Project(JZX2023001).
文摘Photosynthetic bacteria(PSB)has shown significant potential as a drug or drug delivery system owing to their photothermal capabilities and antioxidant properties.Nevertheless,the actualization of their potential is impeded by inherent constraints,including their considerable size,heightened immunogenicity and compromised biosafety.Conquering these obstacles and pursuing more effective solutions remains a top priority.Similar to extracellular vesicles,bacterial outer membrane vesicles(OMVs)have demonstrated a great potential in biomedical applications.OMVs from PSB encapsulate a rich array of bioactive constituents,including proteins,nucleic acids,and lipids inherited from their parent cells.Consequently,they emerge as a promising and practical alternative.Unfortunately,OMVs have suffered from low yield and inconsistent particle sizes.In response,bacteria-derived nanovesicles(BNVs),created through controlled extrusion,adeptly overcome the challenges associated with OMVs.However,the differences,both in composition and subsequent biological effects,between OMVs and BNVs remain enigmatic.In a groundbreaking endeavor,our study meticulously cultivates PSB-derived OMVs and BNVs,dissecting their nuances.Despite minimal differences in morphology and size between PSB-derived OMVs and BNVs,the latter contains a higher concentration of active ingredients and metabolites.Particularly noteworthy is the elevated levels of lysophosphatidylcholine(LPC)found in BNVs,known for its ability to enhance cell proliferation and initiate downstream signaling pathways that promote angiogenesis and epithelialization.Importantly,our results indicate that BNVs can accelerate wound closure more effectively by orchestrating a harmonious balance of cell proliferation and migration within NIH-3T3 cells,while also activating the EGFR/AKT/PI3K pathway.In contrast,OMVs have a pronounced aptitude in anti-cancer efforts,driving macrophages toward the M1 phenotype and promoting the release of inflammatory cytokines.Thus,our findings not only provide a promising methodological framework but also establish a definitive criterion for discerning the optimal application of OMVs and BNVs in addressing a wide range of medical conditions.
基金National Natural Science Foundation of China,Grant/Award Numbers:82102256,82272276,81972019,82102444,88241059,82272281Basic and Applied Basic Research Foundation of Guangdong Province,Grant/Award Numbers:2023A1515012375,2021B1515120036,2021A1515011453,2022A1515012160,2021A1515010949+3 种基金Chinese Postdoctoral Science Foundation,Grant/Award Number:2021M693638Excellent Young Researchers Program of the 5th Affiliated Hospital of SYSU,Grant/Award Number:WYYXQN-2021008National Key Research and Development Program of China,Grant/Award Number:2021YFC2302200Natural Science Fund of Guangdong Province for Distinguished Young。
文摘As a high-risk trauma,deep burns are always hindered in their repair process by decreased tissue regeneration capacity and persistent infections.In this study,we developed a simultaneous strategy for deep burn wounds treatment using functional nanovesicles with antibacterial and tissue remodeling properties,delivered via a click-chemistry hydrogel.An aggregation-induced emission photosensitizer of 4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1-(2-hydroxyethyl)pyridin-1-ium bromide(THB)with excellent photodynamic properties was first prepared,and then combined with readily accessible adipose stem cells-derived nanovesicles to generate the THB functionalized nanovesicles(THB@ANVs).The THB@ANVs showed strong antibacterial activity against Gram-positive bacteria(up to 100%killing rate),and also beneficial effects on tissue remodeling,including promoting cell migration,cell proliferation,and regulating immunity.In addition,we prepared a click-hydrogel of carboxymethyl chitosan for effective delivery of THB@ANVs on wounds.This hydrogel could be injected to conform to the wound morphology while responding to the acidic microenvironment.In vivo evaluations of wound healing revealed that the THB@ANVs hydrogel dressing efficiently accelerated the healing of second-degree burn wounds by reducing bacterial growth,regulating inflammation,promoting early angiogenesis,and collagen deposition.This study provides a promising candidate of wound dressing with diverse functions for deep burn wound repair.
基金supported by National Natural Science Foundation of China(No.82072217,81772135 and U21A20370).
文摘Background:Bacterial infections pose a considerable threat to skin wounds,particularly in the case of challenging-to-treat diabetic wounds.Systemic antibiotics often struggle to penetrate deep wound tissues and topically applied antibiotics may lead to sensitization,necessitating the development of novel approaches for effectively treating germs in deep wound tissues.Neutrophils,the predominant immune cells in the bloodstream,rapidly release an abundance of molecules via degranulation upon activation,which possess the ability to directly eliminate pathogens.This study was designed to develop novel neutrophil cell engineered nanovesicles(NVs)with high production and explore their bactericidal properties and application in promoting infectious wound healing.Methods:Neutrophils were isolated from peripheral blood and activated in vitro via phorbol myristate acetate(PMA)stimulation.Engineered NVs were prepared by sequentially extruding activated neutrophils followed by ultracentrifugation and were compared with neutrophil-derived exosomes in terms of morphology,size distribution and protein contents.The bactericidal effect of NVs in vitro was evaluated using the spread plate technique,LIVE/DEAD backlight bacteria assay and observation of bacterial morphology.The therapeutic effects of NVs in vivo were evaluated using wound contraction area measurements,histopathological examinations,assessments of inflammatory factors and immunochemical staining.Results:Activated neutrophils stimulated with PMA in vitro promptly release a substantial amount of bactericidal proteins.NVs are similar to exosomes in terms of morphology and particle size,but they exhibit a significantly higher enrichment of bactericidal proteins.In vitro,NVs demonstrated a significant bactericidal effect,presumably mediated by the enrichment of bactericidal proteins such as lysozyme.These NVs significantly accelerated wound healing,leading to a marked reduction in bacterial load,downregulation of inflammatory factors and enhanced collagen deposition in a fullthickness infectious skin defect model.Conclusions:We developed engineered NVs derived from activated neutrophils to serve as a novel debridement method targeting bacteria in deep tissues,ultimately promoting infectious wound healing.
基金supported by the National Natural Science Foundation of China(Nos.82273824,31670359 and 82372111)the Liao Ning Revitalization Talents Program(No.XLYC 1905019)。
文摘Natural phytoconstituents exhibit distinct advantages in the management and prevention of inflammatory bowel disease(IBD),attributed to their robust biological activity,multi-target effects,and elevated safety profile.Although promising,the clinical application of phytoconstituents have been impeded by poor water solubility,low oral bioavailability,and inadequate colonic targeting.Recent advancements in nanotechnology has offered prospective avenues for the application of phytoconstituents in the treatment of IBD.A common strategy involves encapsulating or conjugating phytoconstituents with nanocarriers to enhance their stability,prolong intestinal retention,and facilitate targeted delivery to colonic inflammatory tissues.Furthermore,drawing inspiration from the self-assembling nanostructures that emerge during the decoction process of Chinese herbs,a variety of natural active compounds-based nanoassemblies have been developed for the treatment of IBD.They exhibit high drug-loading capacities and surmount the challenges posed by poor water solubility and low bioavailability.Notably,phyto-derived nanovesicles,owing to their unique structure and biological functions,can serve as therapeutic agents or novel delivery vehicles for the treatment of IBD.Consequently,this review provides an extensive overview of emerging phytoconstituent-derived nano-medicines/vesicles for the treatment of IBD,intending to offer novel insights for the clinical management of IBD.
