Salmonella Bacteria Membrane-Fusion Paclitaxel Loaded Liposomes for Enhanced Therapy of Intraperitoneal Metastatic Ovarian Cancer.

ABSTRACT

Ovarian cancer (OvCa) remains a leading cause of gynecological cancer mortality, particularly due to its aggressive peritoneal metastasis. Conventional treatments, including surgery and paclitaxel‐based chemotherapy, are often limited by poor drug penetration into solid tumors, multidrug resistance, and the highly immunosuppressive tumor microenvironment. To overcome these challenges, we engineered a novel bacteria membrane‐fused biomimetic paclitaxel liposome (PLip@DMV) by incorporating bacteria membrane‐derived vesicles from attenuated Salmonella VNP20009. Administered via intraperitoneal injection, PLip@DMV not only delivered paclitaxel effectively but also leveraged the immunomodulatory properties of the Salmonella membrane. This led to significant antitumor immune activation within the metastatic tumor microenvironment, synergistically enhancing therapeutic efficacy and markedly prolonging the survival of tumor‐bearing mice. Furthermore, the enhanced delivery efficiency and sustained‐release characteristics of PLip@DMV resulted in significantly reduced systemic toxicity and tissue accumulation compared to free paclitaxel. Our findings demonstrate that PLip@DMV represents a more efficient, safer, and immunologically potentiated strategy for treating peritoneal metastatic ovarian cancer. This novel biomimetic nanocarrier holds significant promise for improving clinical outcomes in advanced OvCa.