Self‐Carrier Nanoparticles for Delivery of Paclitaxel and IDO Inhibitor to Boost Antitumor Chemo‐Immunotherapy

Abstract

The combination of chemotherapy and immunotherapy holds great potential in clinical treatment of advanced cancers. Whereas, the therapeutic outcome of chemotherapeutic and immune regulator is suboptimal due to their poor tumor availability and severe off‐target toxicity. Herein, self‐carrier nanoparticles (PSMT NPs) integrating a paclitaxel (PTX) prodrug and indoleamine 2,3‐dioxygenase 1 (IDO) inhibitor (1‐methyl‐tryptophan, 1MT) for tumor‐specific chemo‐immunotherapy is constructed. After internalization by cancer cells, PSMT NPs can respond to endogenous redox stimulus, and release PTX and 1MT. The released PTX can not only promote cell apoptosis via the intervention of cell mitosis but also initiate immunogenic cell death to facilitate the recruitment and activation of tumor‐infiltrating cytotoxic T lymphocytes. The concomitant 1MT can inhibit the IDO activity to exhaust regulatory T cells, thereby synergistically activating cytotoxic T lymphocytes. PSMT NPs exhibit potentiated antitumor output toward triple‐negative breast cancer and negligible systemic toxicity. This facile and versatile nanoplatform provides a promising strategy to cooperatively activate antitumor immunity for potentiated chemo‐immunotherapy.