Local precise drug delivery is conducive to improving therapeutic efficacy and minimizing off-target toxicity.Current local delivery approaches are focused mostly on superficial or postoperative tumor lesions,due to t...Local precise drug delivery is conducive to improving therapeutic efficacy and minimizing off-target toxicity.Current local delivery approaches are focused mostly on superficial or postoperative tumor lesions,due to the challenges posed by the inaccessibility of deep-seated tumors.Herein,we report a magnetic continuum soft robot capable of non-invasive and site-specific delivery of prodrug nanoassemblies-loaded hydrogel.The nanoassemblies are co-assembled from redox-responsive docetaxel prodrug and oxaliplatin prodrug,and subsequently embedded into a hydrogel matrix.The hydrogel precursor and crosslinker are synchronously delivered using the soft robot under magnetic guidance and in situ crosslinked at the gastric cancer lesions,forming a drug depot for sustained release and long-lasting treatment.As the hydrogel gradually degrades,the nanoassemblies are internalized by tumor cells.The redox response ability enables them to be selectively activatedwithin tumor cells to trigger the release of docetaxel and oxaliplatin,exerting a synergistic anti-tumor effect.We find that the combination effectively induces immunogenic cell death of gastric tumor,enhancing antitumor immune responses.This strategy offers an intelligent and controllable integration platform for precise drug delivery and combined chemo-immunotherapy.展开更多
Cells and exosomes derived from them are extensively used as biological carrier systems.Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins,wh...Cells and exosomes derived from them are extensively used as biological carrier systems.Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins,while exosomes,due to their small size,cross barriers and penetrate tumors efficiently.However,challenges remain,cells’large size restricts tissue penetration,and exosomes have limited targeting accuracy and short circulation times.To address these challenges,we developed a novel concept termed exosomal spheres.This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine(PS)and linked via pH-sensitive bonds for drug delivery applications.The study demonstrated that,compared with exosomes,the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine,thereby minimizing immune clearance.Moreover,the increased expression of P-selectin promoted adhesion to circulating tumor cells,thereby enhancing targeting efficiency.Upon reaching the tumor site,the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment,leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets.These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.展开更多
The tumor microenvironment-sensitive prodrug-based nanoparticles(NPs)have emerged as a promising drug delivery system(DDS).The shape of these particles plays a crucial role in their in vivo behavior.However,non-spheri...The tumor microenvironment-sensitive prodrug-based nanoparticles(NPs)have emerged as a promising drug delivery system(DDS).The shape of these particles plays a crucial role in their in vivo behavior.However,non-spherical organic NPs are rarely reported due to the inherent flexibility and variability of organic molecules.Herein,we fabricate reduction-sensitive prodrug NPs and explore the impact of their morphology properties on their in vivo fate.Prodrugs are self-assembled into spherical NPs with distearoyl phosphoethanolamine-PEG2000(DSPE-PEG2k),or into rod-shaped NPs with D-a-tocopherol polyethylene glycol 2000 succinate(TPGS2k)due to the stronger binding energy.In comparison with spherical NPs,the endocytosis of rod-shaped NPs predominantly relies on caveolae-mediated pathways rather than clathrin-mediated ones,potentially avoiding degradation by lysosomes.Additionally,the rod-shaped NPs exhibit prolonged circulation time,increased tumor accumulation,and enhanced antitumor ability.Our current findings reveal the significant effect of particle shape on the behavior of prodrug NPs and introduce a novel paradigm for high-efficacy cancer therapy of prodrug NPs.展开更多
Smart catalysts that can simultaneously utilize multiple energy sources will have a significant positive impact on the inefficiencies of conventional environmental remediation approaches,and will address their high en...Smart catalysts that can simultaneously utilize multiple energy sources will have a significant positive impact on the inefficiencies of conventional environmental remediation approaches,and will address their high energy demands.In this work,we have manufactured multiferroic magnetoelectric photocatalysts that can be simultaneously activated using multiple energy sources for the degradation of organic pollutants.The catalysts are composed of CoFe2O4@BiFeO3(CFO@BFO)nanooctahedrons(NOs),CFO@BFO nanocubes(NCs),and CFO@BFO nanowires(NWs),and were successful in harnessing energy from three different energy sources,including UV-vis light,acoustically mediated mechanical vibrations and magnetic fields.The CFO@BFO NOs displayed the most enhanced degradation,reaching 93%,96%,and 99%degradation of RhB dye within 1 h under light,ultrasound,and magnetic fields,respectively.When these energy sources were used simultaneously,significantly increased reaction rates were observed compared to the single-energy source stimulation.Results of radical trapping experiments indicate that radical species i.e.,OH·and O2·^-play a dominant role in catalytic degradation of organic pollutant,RhB,under all three stimuli.These results will contribute significantly to the development of new environmental technologies that are highly versatile in nature and able to adapt to changing environments to deliver efficient environmental remediation.展开更多
基金supported by National Natural Science Foundation of China(No.82161138029)Liaoning Revitalization Talents Program(No.XLYC2402040)the Project of China-Japan Joint International Laboratory of Advanced Drug Delivery System Research and Translation of Liaoning Province(No.2024JH2/102100007).
文摘Local precise drug delivery is conducive to improving therapeutic efficacy and minimizing off-target toxicity.Current local delivery approaches are focused mostly on superficial or postoperative tumor lesions,due to the challenges posed by the inaccessibility of deep-seated tumors.Herein,we report a magnetic continuum soft robot capable of non-invasive and site-specific delivery of prodrug nanoassemblies-loaded hydrogel.The nanoassemblies are co-assembled from redox-responsive docetaxel prodrug and oxaliplatin prodrug,and subsequently embedded into a hydrogel matrix.The hydrogel precursor and crosslinker are synchronously delivered using the soft robot under magnetic guidance and in situ crosslinked at the gastric cancer lesions,forming a drug depot for sustained release and long-lasting treatment.As the hydrogel gradually degrades,the nanoassemblies are internalized by tumor cells.The redox response ability enables them to be selectively activatedwithin tumor cells to trigger the release of docetaxel and oxaliplatin,exerting a synergistic anti-tumor effect.We find that the combination effectively induces immunogenic cell death of gastric tumor,enhancing antitumor immune responses.This strategy offers an intelligent and controllable integration platform for precise drug delivery and combined chemo-immunotherapy.
基金support from National Key R&D Program of China(No.2022YFE0111600)National Natural Science Foundation of China(No.82273874)Liaoning Revitalization Talents Program(No.XLYC22202019,China).
文摘Cells and exosomes derived from them are extensively used as biological carrier systems.Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins,while exosomes,due to their small size,cross barriers and penetrate tumors efficiently.However,challenges remain,cells’large size restricts tissue penetration,and exosomes have limited targeting accuracy and short circulation times.To address these challenges,we developed a novel concept termed exosomal spheres.This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine(PS)and linked via pH-sensitive bonds for drug delivery applications.The study demonstrated that,compared with exosomes,the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine,thereby minimizing immune clearance.Moreover,the increased expression of P-selectin promoted adhesion to circulating tumor cells,thereby enhancing targeting efficiency.Upon reaching the tumor site,the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment,leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets.These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.
基金This research was supported by National Natural Science Foundation of China(Nos.82273874 and 82404561)Liaoning Revitalization Talents Program(No.XLYC22202019)+4 种基金the China National Postdoctoral Program for Innovative Talents(No.BX20240233)the Postdoctoral Fellowship Program(Grade B)of China Postdoctoral Science Foundation(No.GZB20240179)the China Postdoctoral Science Foundation(No.2023MD744230)Doctoral Scientific Research Launching Fund Project of Liaoning province(No.2024-BS-075)Prospective Basic research project of 2024 Scientific Research Project of Liaoning Department of Education(No.LJ212410163042).
文摘The tumor microenvironment-sensitive prodrug-based nanoparticles(NPs)have emerged as a promising drug delivery system(DDS).The shape of these particles plays a crucial role in their in vivo behavior.However,non-spherical organic NPs are rarely reported due to the inherent flexibility and variability of organic molecules.Herein,we fabricate reduction-sensitive prodrug NPs and explore the impact of their morphology properties on their in vivo fate.Prodrugs are self-assembled into spherical NPs with distearoyl phosphoethanolamine-PEG2000(DSPE-PEG2k),or into rod-shaped NPs with D-a-tocopherol polyethylene glycol 2000 succinate(TPGS2k)due to the stronger binding energy.In comparison with spherical NPs,the endocytosis of rod-shaped NPs predominantly relies on caveolae-mediated pathways rather than clathrin-mediated ones,potentially avoiding degradation by lysosomes.Additionally,the rod-shaped NPs exhibit prolonged circulation time,increased tumor accumulation,and enhanced antitumor ability.Our current findings reveal the significant effect of particle shape on the behavior of prodrug NPs and introduce a novel paradigm for high-efficacy cancer therapy of prodrug NPs.
基金This work has been financed by the European Research Council Starting Grant“Magnetoelectric Chemonanorobotics for Chemical and Biomedical Applications(ELECTROCHEMBOTS)”,by the ERC grant agreement no.336456.
文摘Smart catalysts that can simultaneously utilize multiple energy sources will have a significant positive impact on the inefficiencies of conventional environmental remediation approaches,and will address their high energy demands.In this work,we have manufactured multiferroic magnetoelectric photocatalysts that can be simultaneously activated using multiple energy sources for the degradation of organic pollutants.The catalysts are composed of CoFe2O4@BiFeO3(CFO@BFO)nanooctahedrons(NOs),CFO@BFO nanocubes(NCs),and CFO@BFO nanowires(NWs),and were successful in harnessing energy from three different energy sources,including UV-vis light,acoustically mediated mechanical vibrations and magnetic fields.The CFO@BFO NOs displayed the most enhanced degradation,reaching 93%,96%,and 99%degradation of RhB dye within 1 h under light,ultrasound,and magnetic fields,respectively.When these energy sources were used simultaneously,significantly increased reaction rates were observed compared to the single-energy source stimulation.Results of radical trapping experiments indicate that radical species i.e.,OH·and O2·^-play a dominant role in catalytic degradation of organic pollutant,RhB,under all three stimuli.These results will contribute significantly to the development of new environmental technologies that are highly versatile in nature and able to adapt to changing environments to deliver efficient environmental remediation.
