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

Abstract 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 β‐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.