JQ1-Loaded Polydopamine Nanoplatform Inhibits c-MYC/Programmed Cell Death Ligand 1 to Enhance Photothermal Therapy for Triple-Negative Breast Cancer.

Abstract

Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy; however, the response of triple-negative breast cancer (TNBC) to PD-L1 antibodies is limited. To address this challenge, we use the bromodomain and extra-terminal inhibitor JQ1 to down-regulate the expression of PD-L1 and thus elicit the immune response to TNBC instead of using antibodies to block PD-L1. JQ1 also inhibits the growth of TNBC as a targeted therapeutic agent by inhibiting the BRD4-c-MYC axis. The polydopamine nanoparticles (PDMNs) are introduced as a biodegradable and adaptable platform to load JQ1 and induce photothermal therapy (PTT) as another synergistic therapeutic modality. Because the JQ1-loaded PDMNs (PDMN-JQ1) are self-degradable and release JQ1 continuously, this synergistic treatment can lead to remarkable activation of cytotoxic T lymphocytes and induce a strong immune-memory effect to protect mice from tumor re-challenge. Taken together, our study demonstrates a compact and simple nanoplatform for triple therapy, including targeted therapy, PTT, and immunotherapy, for TNBC treatment.