PDL1 Monoclonal Antibody-Modified mPEG–PLGA-NH2 Nanocomposite Loaded with Heterophyllin B for the Treatment of Gastric Cancer

Immune checkpoint inhibitors (ICIs) show effectiveness in gastric cancer (GC) treatment, yet enhancing their efficacy remains challenging. We encapsulated the anticancer compound Heterophyllin B (HB) in mPEG–PLGA-NH2 nanoparticles (NPs), modified with αPDL1, forming mPEG–PLGA-NH2@HB-αPDL1 NPs. These NPs displayed low toxicity to GES-1 cells and good blood compatibility. They effectively inhibited GC cell malignant phenotypes and downregulated PD-L1 expression via the PI3K/AKT pathway. In GC allograft mice, the HB and αPDL1 combination therapy outperformed monotherapy, with the NPs showing better efficacy than free drugs. Additionally, the NPs improved the tumor immune microenvironment. H&E staining confirmed no significant toxicity to major mouse organs. Thus, mPEG–PLGA-NH2@HB-αPDL1 offers a promising strategy for optimizing ICI therapy in GC treatment.

免疫检查点抑制剂（Immune checkpoint inhibitors, ICIs）在胃癌（gastric cancer, GC）治疗中已展现出一定疗效，但进一步提升其治疗效果仍颇具挑战。本研究将抗癌化合物异叶素B（Heterophyllin B, HB）包载于mPEG–PLGA-NH2纳米颗粒（NPs）中，并通过αPDL1对其进行修饰，制备得到mPEG–PLGA-NH2@HB-αPDL1 NPs。该纳米颗粒对GES-1细胞毒性较低，且具备良好的血液相容性。其可有效抑制胃癌细胞的恶性表型，并通过PI3K/AKT通路下调PD-L1的表达。在胃癌异体移植小鼠模型中，HB与αPDL1联合治疗的效果优于单一疗法，且纳米颗粒的治疗效果优于游离药物。此外，该纳米颗粒可改善肿瘤免疫微环境。苏木精-伊红（H&E）染色结果证实，其对小鼠主要脏器无明显毒性。综上，mPEG–PLGA-NH2@HB-αPDL1为优化胃癌免疫检查点抑制剂治疗提供了极具潜力的策略。