Gastric cancer is a highly heterogeneous and aggressive malignancy,with conventional therapies often hampered by poor drug targeting and an immunosuppressive tumor microenvironment(TME).To address these limitations,we...Gastric cancer is a highly heterogeneous and aggressive malignancy,with conventional therapies often hampered by poor drug targeting and an immunosuppressive tumor microenvironment(TME).To address these limitations,we developed a biomimetic nanoplatform(PLGA-UA@MA)composed of poly(lactic-co-glycolic acid)(PLGA)nanoparticles encapsulating the natural antitumor agent ursolic acid(UA),further cloaked with homologous gastric cancer cell membranes doped with the immunoadjuvant monophosphoryl lipid A(MPLA).This engineered system synergistically combines tumor-specific targeting,immune modulation,and stimuliresponsive drug release,presenting a precision therapeutic strategy for gastric cancer.PLGA-UA@M-A exhibits selective homing to primary tumor sites,facilitated by membrane fusion-mediated enhanced cellular uptake.In vitro studies demonstrated potent inhibition of MFC gastric cancer cell proliferation,induction of apoptosis,and suppression of metastatic behavior,underscoring its enhanced antitumor efficacy.Moreover,the nanoplatform triggered immunogenic cell death(ICD),while MPLA acted as an immunostimulant to promote dendritic cell maturation and T-cell priming—effectively reprogramming the immunosuppressive TME.In vivo evaluations confirmed excellent tumor accumulation,robust antitumor activity,and negligible systemic toxicity,highlighting its favorable biosafety profile.Collectively,PLGA-UA@M-A represents a multifunctional biomimetic delivery system that integrates chemotherapy with immune activation,offering a promising therapeutic paradigm for gastric cancer treatment.展开更多
基金supported by the National Natural Science Foundation of China(No.82360498)Gansu Joint Scientific Research Fund Major Project(No.23JRRA1537)+5 种基金the 2025 Central-Guided Local Science and Technology Development Found(No.25ZYJA003)Gansu Provincial Health Industry Science and Technology Innovation Major Project(No.GSWSZD2024-01)Gansu Province Key Talent Project(No.2025RCXM067)2024 Gansu Provincial Hospital Special Fund of NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor(No.23GSSYA-10)the 2021 Central-Guided Local Science and Technology Development Found(No.ZYYDDFFZZJ-1)Zhejiang Provincial Natural Science Foundation of China(No.LTGY23H160032).
文摘Gastric cancer is a highly heterogeneous and aggressive malignancy,with conventional therapies often hampered by poor drug targeting and an immunosuppressive tumor microenvironment(TME).To address these limitations,we developed a biomimetic nanoplatform(PLGA-UA@MA)composed of poly(lactic-co-glycolic acid)(PLGA)nanoparticles encapsulating the natural antitumor agent ursolic acid(UA),further cloaked with homologous gastric cancer cell membranes doped with the immunoadjuvant monophosphoryl lipid A(MPLA).This engineered system synergistically combines tumor-specific targeting,immune modulation,and stimuliresponsive drug release,presenting a precision therapeutic strategy for gastric cancer.PLGA-UA@M-A exhibits selective homing to primary tumor sites,facilitated by membrane fusion-mediated enhanced cellular uptake.In vitro studies demonstrated potent inhibition of MFC gastric cancer cell proliferation,induction of apoptosis,and suppression of metastatic behavior,underscoring its enhanced antitumor efficacy.Moreover,the nanoplatform triggered immunogenic cell death(ICD),while MPLA acted as an immunostimulant to promote dendritic cell maturation and T-cell priming—effectively reprogramming the immunosuppressive TME.In vivo evaluations confirmed excellent tumor accumulation,robust antitumor activity,and negligible systemic toxicity,highlighting its favorable biosafety profile.Collectively,PLGA-UA@M-A represents a multifunctional biomimetic delivery system that integrates chemotherapy with immune activation,offering a promising therapeutic paradigm for gastric cancer treatment.
