Immunostimulatory photochemotherapeutic nanocapsule for enhanced colon cancer treatment

Abstract

Immunotherapy has made great progress in recent years while most cancer patients cannot benefit from it. Photochemotherapy combination strategy holds great promise for developing novel immunotherapy for the patients bearing immunosuppressive tumors such as colon cancer. In this research, a novel core/shell-structured polydopamine (PDA)-based nanoplatform is constructed to load two Food and Drug Administration (FDA)-approved cytotoxic drugs, i.e. immunostimulatory doxorubicin (Dox) and immunomodulatory curcumin (Cur) to achieve immunostimulatory photochemotherapy of primary colon tumors upon 808 nm near infrared (NIR) irradiation (1 W/cm2 for 5 min) and subsequent prevention of rechallenged distant colon tumors. The experimental data have shown that PDA-mediated photothermal therapy (PTT) synergized two therapeutic drugs in inducing colon cancer cell death and very efficiently inhibited the primary tumor growth (by ∼92%) at very low doses of therapeutics (0.25, 5, and 30 mg/kg of Dox, Cur, and PDA, respectively). More significantly, the combined photochemotherapy promoted strong adaptive antitumor immune responses and successfully prevented tumorigenesis in the setting of tumor rechallenge model. Our research has thus demonstrated the promising efficacy of this photochemotherapeutic nanoformulation for colon cancer treatment and provided a way to improve immunostimulatory effects of conventional chemotherapeutic drugs.