Decomposable black phosphorus nano-assembly for controlled delivery of cisplatin and inhibition of breast cancer metastasis

Abstract

Novel platforms for cisplatin delivery with a controllable manner and combinable with other treatment modality to achieve synergistic antitumor effect and inhibition metastasis for treatment of triple negative breast cancer (TNBC) are highly desirable. Herein, we report a black phosphorus (BP) nanosheets-based nano-assembly which consists of cisplatin, BP, polydopamine (PDA) and hyaluronic acid (HA), cisplatin/BP/PDA-HA (CBPH), for controlled delivery of cisplatin and inhibition tumor growth as well as lung metastasis of TNBC. For constructing CBPH, the surface of BP was dual modified by PDA and HA, resulting in enhanced stability, tumor target ability and photothermal efficiency of BP. Cisplatin was released in response both to internal and external stimuli existed in tumor microenvironment, including low pH, hydrogen peroxide and NIR light, as accompanied by decomposition of BP. In vitro experiments demonstrated CBPH-treated 4 T1 cells showed elevated intracellular content of Pt and Pt-DNA adduct, which was further improved when exposure to NIR light, leading to potent antitumor effect in a synergistic pattern. Anti-metastasis studies in 2D monolayers and 3D organoids revealed that CBPH plus NIR light treatment exhibited significantly decreased migration, invasion and regrowth ability of 4 T1 cells. Furthermore, TNBC-bearing mice with systemic administrate of CBPH showed enhanced tumor accumulation of cisplatin and light-triggered inhibition of tumor growth at primary site and lung metastasis, with alleviated toxicity. But CBPH is yet to be optimized for realizing smart cisplatin delivery in response to acidic and redox stimuli in vivo. Collectively, our study demonstrates that this novel BP-based nano-assembly with controllable tumor delivery of cisplatin and metastasis inhibition of breast cancer expand the use of BP in biomedicine field and hold great promise for further development.