Photothermal-Controlled Nanotubes with Surface Charge Flipping Ability for Precise Synergistic Therapy of Triple-Negative Breast Cancer

Owing to the highly malignant and invasive innate character of triple-negative breast cancers (TNBCs), it is easy to relapse after chemotherapy; thus, there are still no effective and specific targeted therapies. In this study, a carbon nanotube (CNT)-based nanosystem Se@CNTs with surface charge flipping and targeted ability is rationally designed and successfully synthesized for precise chemo-photothermal synergistic therapy of TNBCs. The acid-labile beta-carboxylic acid group is used to reversibly functionalize the amine groups, thus forming charge-reversal nanoparticles to enhance the bioresponsive cellular uptake. The internalized Se@CNTs combined with laser irradiation induces reactive oxygen species (ROS) overproduction, which activates apoptosis-related proteins to trigger cancer cell apoptosis synergistically. Meanwhile, Se@CNTs also suppresses the invasion and migration of TNBC cells by regulating the related signaling pathways. Importantly, in combination with laser irradiation, Se@CNTs effectively inhibits the tumor growth, as demonstrated by the high tumor ablation activity in vivo through chemo-phototherapy, but shows no significant histological change in the main organs. Taken together, this study provides a strategy for rational design of next-generation nanomedicines for precise chemo-photothermal synergistic therapy of malignant TNBCs.