Biodegradable nanoparticle-enhanced chemoimmunotherapy based on precise tumor killing and tumor microenvironment regulation strategy

Abstract

Although chemotherapy-based immunotherapy has promoted tumor therapeutic effects, it is counteracted by the negative immune regulation of the tumor microenvironment (TME). Herein, pH-responsive SN-38/CXB@mPEG-PAE nanocomplexes were fabricated to improve the immunosuppressive tumor microenvironment (ITM), thereby enhancing antitumor activity. In the acidic TME, chemotherapeutic drug 7-ethyl-10-hydroxycamptothecin (SN-38) and celecoxib (CXB, an inhibitor of cyclooxygenase-2) were released, indicating that these nanocomplexes precisely targeted tumor cells. Moreover, the released SN-38, in addition to directly eliminating cancer cells by inducing tumor cell apoptosis and cell cycle arrest, induced immunogenic cell death (ICD) in vitro. The released CXB could further activate dendritic cells (DCs) by inhibiting the COX-2/PGE₂ axis, which synergistically activated the immune system to promote treatment efficacy. This study provides a novel functional nanoplatform to improve the ITM for enhanced chemotherapy-based immunotherapy.