Dual-responsive triple-helix β-glucan-based self-assembled supramolecule for combination chemo-photothermal therapy against lung metastatic triple negative breast cancer.

The development of multifunctional therapies with targeted release materials is desirable for overcoming the high aggressiveness and poor prognosis of triple-negative breast cancer (TNBC). Herein, we have designed a self-assembled supramolecule (BSD), in which SWNTs can be wrapped by triple-helix β-Glucan (BFP) in a self-assembled manner, and doxorubicin (DOX) is attached onto SWNTs by means of π-stacking and hydrophobic interactions with high drug encapsulation efficiency (89.3 %). BFP could significantly improve the dispersion and stability of SWNTs and DOX, and reduce toxicity. BSD provides a drug-targeting mechanism due to the pH-responsive and near-infrared radiation (NIR) thermal-responsive release of DOX, and BSD displayed excellent photo-thermal conversion effect and cyclic stability, and exhibited higher antitumor activity under near-infrared radiation than chemotherapy alone. Photothermal therapy mainly blocked the synthesis of nutrients required for tumor DNA replication, while chemotherapy markedly induced oxidative stress production, which ultimately exacerbated DNA damage of tumor cells. As a result, the combined effect of chemo-photothermal therapy ultimately promote tumor cell apoptosis and suppress the growth of primary tumor and metastasis to the lungs in vitro and in vivo. This study provides a promising pH/NIR thermal-responsive sustained prodrug for combined chemo-photothermal therapy against aggressive triple negative breast cancer in practical therapy.