Tumor Cell Targeting and Responsive Nanoplatform for Multimodal-Imaging Guided Chemodynamic/Photodynamic/Photothermal Therapy toward Triple Negative Breast Cancer

Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with ineffective treatment and poor prognosis. It is in great demand to develop a novel theranostic strategy for accurate diagnosis and targeted treatment of TNBC. In the present study, one nanoplatform (HA-ICG-Fe-PDA), endowed with multimodal imaging-guided chemodynamic/photodynamic/photothermal (CDT/PDT/PTT) synergistic therapy capacity toward TNBC, was innovatively constructed. The nanoplatform was prepared by covalently conjugating ICG-decorated hyaluronic acid (HA) on Fe³⁺-chelated polydopamine (PDA). HA facilitated the targeting and accumulating of the nanoplatform in tumor tissue and cells of TNBC, thus producing enhanced magnetic resonance signal. Upon entering into TNBC cells, the intracellular hyaluronidase-catalyzed cleavage of HA-ICG-Fe-PDA activated the prequenched near-infrared (NIR) fluorescence signal, allowing for the activatable NIR fluorescence imaging. On the other hand, Fe³⁺ in the nanoplatform could be reduced to reactive Fe²⁺ in tumor microenvironment, guaranteeing efficient Fenton reaction-mediated CDT. The combination of ICG with Fe-PDA enhanced the NIR absorption of the nanoplatform so that considerable PTT/PDT and photothermal imaging were achieved under 808 nm laser irradiation. In vitro and in vivo experiments have verified that the proposed nanoplatform integrates the potential of TNBC-targeting, precise NIR fluorescence/magnetic resonance/photothermal trimodal imaging, efficient treatment via synergistic CDT/PDT/PTT, as well as excellent biocompatibility. Therefore, this multifunctional nanoplatform provides a simple and versatile strategy for imaging-guided theranostics of TNBC.