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 aggressivesubtypeof breast cancer, with ineffective treatment and poor prognosis. Itis in great demand to develop a novel theranostic strategy for accuratediagnosis and targeted treatment of TNBC. In the present study, onenanoplatform (HA-ICG-Fe-PDA), endowed with multimodal imaging-guidedchemodynamic/photodynamic/photothermal (CDT/PDT/PTT) synergistic therapycapacity toward TNBC, was innovatively constructed. The nanoplatformwas prepared by covalently conjugating ICG-decorated hyaluronic acid(HA) on Fe3+-chelated polydopamine (PDA). HA facilitatedthe targeting and accumulating of the nanoplatform in tumor tissueand cells of TNBC, thus producing enhanced magnetic resonance signal.Upon entering into TNBC cells, the intracellular hyaluronidase-catalyzedcleavage of HA-ICG-Fe-PDA activated the prequenched near-infrared(NIR) fluorescence signal, allowing for the activatable NIR fluorescenceimaging. On the other hand, Fe3+ in the nanoplatform couldbe reduced to reactive Fe2+ in tumor microenvironment,guaranteeing efficient Fenton reaction-mediated CDT. The combinationof ICG with Fe-PDA enhanced the NIR absorption of the nanoplatformso that considerable PTT/PDT and photothermal imaging were achievedunder 808 nm laser irradiation. In vitro and in vivo experiments have verified that the proposed nanoplatformintegrates the potential of TNBC-targeting, precise NIR fluorescence/magneticresonance/photothermal trimodal imaging, efficient treatment via synergisticCDT/PDT/PTT, as well as excellent biocompatibility. Therefore, thismultifunctional nanoplatform provides a simple and versatile strategyfor imaging-guided theranostics of TNBC.