In situ targeting nanoparticles-hydrogel hybrid system for combined chemo-immunotherapy of glioma

It is well known that glioma is currently the most malignant brain tumor. Because of the existence of blood-brain barrier (BBB) and tumor cell heterogeneity, systemic chemotherapy exerts unsatisfied therapeutic effect for the treatment of glioma after surgical resection and may even damage the body's immune system. Here, we developed an in situ sustained-release hydrogel delivery system for combined chemo-immunotherapy of glioma by combined chemotherapy drug and immunoadjuvant through the resection cavity local delivery. Briefly, glioma homing peptide modified paclitaxel targeting nanoparticles (PNP_PTX) and mannitolated immunoadjuvant CpG targeting nanoparticles (MNP_CpG) were embedded into PLGA₁₇₅₀-PEG₁₅₀₀-PLGA₁₇₅₀ thermosensitive hydrogel framework (PNP_PTX&MNP_CpG@Gel). The in vitro and in vivo results showed that the targeting nanoparticles-hydrogel hybrid system could cross-link into a gel drug reservoir when injected into the resection cavity of glioma. And then, the sustained-release PNP_PTX could target the residual infiltration glioma cells and produce tumor antigens. Meanwhile, MNP_CpG targeted and activated the antigen-presenting cells, which enhanced the tumor antigen presentation ability and activated CD8⁺T and NK cells to reverse immunosuppression of glioma microenvironment. This study indicated that the PNP_PTX&MNP_CpG@Gel system could enhance the therapeutic effect of glioma by chemo-immunotherapy.