Light-Responsive Hydrogel with Nano-Microstructures for Bacteria Eradication and Tumor Therapy

The insufficient immunogenicity of the tumor microenvironment coupled with intratumoral bacteria are important causes of poor prognosis in osteosarcoma patients. The strategy for eliminating intratumoral bacteria and enhancing the immunogenicity of the tumor microenvironment is key to improving the therapeutic effect in osteosarcoma treatment. In this study, light-responsive hydrogel with nano-microstructures was constructed by microfluidic technology, enabling targeting the eradication of tumor bacteria and optically controlled programmed reconstruction of tumor microenvironment, which was composed of a hyaluronic acid-coated microshell and a polyadenylation drug-loaded mesoporous silica nanoparticles core modified by bacteria-targeting LPS antibody and heat-responsive plate. This study aims to promote the selective retention and photoresponsive release of drugs in osteosarcoma and finally realize the combined effect of antibacterial and antineoplastic photoimmunochemotherapy. The distinctive structure of the hydrogel with nano-microstructures enables inhibiting the progression of osteosarcoma, simultaneously eliminating bacteria and enhancing the immunogenicity of the tumor microenvironment. In vitro and in vivo experiments showed that the hydrogel with nano-microstructures improved the therapeutic effect on osteosarcoma by eliminating intratumoral bacteria through the synergistic action of photoimmunochemotherapy. On the other hand, the hydrogel with nano-microstructures activated the expression of CD4 and CD8 in osteosarcoma, regulated the tumor microenvironment, and enhanced the antineoplastic effect. In summary, the hydrogel with nano-microstructures can achieve the combined effect of antibacterial and antineoplastic photoimmunochemotherapy by eliminating the intratumoral bacteria and regulating the microenvironment, which provides an idea for the clinical application of injectable hydrogel with nano-microstructures in the treatment of osteosarcoma.