Preparation of pH-Sensitive Polysaccharide-Small Molecule Nanoparticles and Their Applications for Tumor Chemo- and Immunotherapy.

Hydrophobic chemotherapy drugs face significant challenges in cancer treatment, including low bioavailability, unavoidable toxic side effects, and the development of drug resistance. To address these issues, a multifunctional nanoplatform was developed for cancer therapy, aimed at achieving effective drug delivery and enhancing antitumor efficacy. polysaccharide (PCP), a natural polymer known for its immunomodulatory properties, was utilized as an immunoreactive vector for drug delivery after being cross-linked with 1,4-phenylenebisboronic acid (BDBA). Subsequently, a small-molecule chemotherapy drug, esculetin (EL), was confirmed through density functional theory (DFT) simulations to be encapsulated within the PCP-BDBA nanoparticles via weak interactions. The results demonstrated that the synthesized nanoparticles were spherical, with an average particle size of 162.0 nm. In addition to exhibiting excellent stability, the nanoparticles also displayed pH-responsive drug release properties. experiments indicated that EL@PCP-BDBA NPs exhibited antitumor effects. Furthermore, EL@PCP-BDBA NPs showed superior antitumor activity compared to EL at the cellular level. Additionally, EL@PCP-BDBA NPs were found to increase intracellular reactive oxygen species (ROS) levels, induce cell apoptosis, and suppress cell migration to combat cancer. Meanwhile, EL@PCP-BDBA NPs enhanced immune function . In summary, this study developed a nano-pharmaceutical that combined chemotherapy and immunotherapy functions, which was considered a promising tool for cancer therapy.