Cell membrane-camouflaged nanoparticles boost combined chemo/immunotherapy for gastric cancer

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@M-A) 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 stimuli-responsive 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. <i>In vitro</i> 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. <i>In vivo</i> 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.