NIR nanoadjuvant-mediated synergistic chemo/photothermal therapy with self-amplified immunogenic cell death to augment antitumor efficiency

Abstract

Photothermal therapy (PTT) can reprogram the immunosuppressive “cold” tumor microenvironment (TME) by releasing heat shock protein (HSP)-related danger-associated molecular patterns (DAMPs) into an immunoreactive “hot” TME for immunogenic cell death (ICD). However, PTT is hampered by a lack of irradiation laser power with obvious energy loss at the tumor site, which results in a limited ICD effect. To overcome this obstacle, chemotherapy-based doxorubicin hydrochloride (DOX) can evoke an antitumor immune response by expressing DAMPs, such as calreticulin (CRT), high-mobility-group box 1 (HMGB1), and adenosine triphosphate (ATP) to initiate intra-tumoral ICD, which also can induce DNA damage to promote cellular apoptosis undoubtedly improving the PTT effect for cascaded amplified tumor ablation outcome. Herein we prepare near-infrared nanoadjuvant CA DOX NPs, which are constructed using near-infrared (NIR) phototherapeutic agent CA and clinical chemotherapeutic drug DOX to cooperatively fight cancer. The CA DOX NPs display enhanced PTT efficiency owing to the strengthened apoptosis and ICD with DNA damage based on DOX. More importantly, the chemotherapeutic effects of DOX can also be specifically promoted during cellular heat stress. Hence, the multimodal NIR CA DOX NPs can initiate synergistic therapeutic outcomes to augment the cancer ablation effect, which provides a promising avenue in cancer therapy for further preclinical investigation.