LAUSR

Abstract The severe issues facing conventional therapies for triple negative breast cancer (TNBC), such as poor response rate and side effects, calls for new strategies to realize better prognosis. Owing to the merits of good efficacy, safety and facile implementation, phototherapy represents an attractive modality for this goal. Black phosphorus (BP) is a class of novel interesting materials for biomedical uses with advantages of biodegradability and optical activity. However, its stability, safety and biological performance remained to be further optimized. In this work, we report a novel light-responsive nanosystem, named Cy@HBPN, for fluorescence imaging-guided synergistic photothermal and photodynamic therapy (PTT/PDT) against TNBC. Hyaluronic acid was coated onto NIR dye(cypate)-loaded BPN, resulting in favorable stability, excellent delivery efficiency into tumor cells and photothermal and photodynamic potential. Importantly, the safety profile of HBPN was greatly improved, compared to the counterpart without HA coating. Following NIR irradiation, localized generation of singlet oxygen and hyperthermia by Cy@HBPN had a significant antitumor effect against both 4T1 cell monolayers and 3D organoids in vitro. Additionally, Cy@HBPN showed significantly enhanced accumulation in tumor tissue and subsequently promoted light-triggered tumor ablation in a mouse model of TNBC. Taken together, this study demonstrates that novel nanophototherapeutics with great stability and safety profile such as Cy@HBPN represent a promising platform for imaging-guided phototherapy for breast cancer treatment.