Biocompatible Astragalus polysaccharide-based nanogels for oncology: synthesis, characterization, and therapeutic potential.

In recent years, drug delivery systems have become an important platform for cancer diagnosis and treatment. However, developing a novel nanoplatform that synergistically integrates multimodal therapies for precision tumor treatment remains a significant challenge. To address this, we employed Astragalus polysaccharide (ASP) with immunomodulatory function as the framework to load podophyllotoxin (PPT) and IR780, and constructed a novel ROS/GSH/NIR triple-response nanoplatform (IR780@PPTASP). Under simulated tumor microenvironment conditions, IR780@PPTASP underwent controlled collapse and drug release. The loaded IR780 photosensitizer endowed IR780@PPTASP with exceptional photothermal and photodynamic properties. To further investigate the molecular mechanism of IR780@PPTASP on A549 cells, we conducted a series of experiments. The results demonstrated that IR780@PPTASP could significantly inhibit A549 cell proliferation and migration, induce the production of reactive oxygen species (ROS), and promote A549 cell apoptosis. Furthermore, in vivo experiments revealed that IR780@PPTASP could effectively inhibit the proliferation and metastasis of zebrafish transplanted tumors. Notably, IR780@PPTASP promoted the release of nitric oxide (NO), and increased the expression of CD40, CD80, CD86, and MHC-II, thereby promoting macrophage maturation and activating T cell function. The developed ROS/GSH/NIR triple-response nanoplatform enables a synergistic approach to chemo-phototherapy-immunotherapy, offering significant promise for the precision treatment of tumors, effectively achieving multiple therapeutic effects simultaneously.