Black Phosphorus Nanosheets-Based Platform For Targeted Chemo-Photothermal Synergistic Cancer Therapy

As a new member of two-dimensional (2D) nanomaterials, black phosphorus (BP) has been considered as efficient photothermal therapy (PTT) agents owing to its excellent photothermal efficiency and biodegradability. Herein, a multifunctional nanoplatform based on black phosphorus nanosheets (BP NSs) was developed for chemo-photothermal synergistic cancer therapy. The BP NSs were successfully prepared by a liquid exfoliation technique. Doxorubicin (DOX), as a model drug, was loaded into the cavity of poly (amidoamine) (PAMAM) dendrimer using thin film hydration method. Then, PAMAM@DOX was coated on the surface of BP NSs using an electrostatic adsorption method that combined bath sonication with magnetic stirring. Hyaluronic acid (HA) was also modified onto the BP NS-PAMAM@DOX through electrostatic adsorption. PAMAM and HA layer could effectively isolate BP NSs from water and air to improve physiological stability. BP NSs and BP NS-PAMAM@DOX-HA were characterized by particle size, zeta potential, morphology, UV-vis-NIR absorption spectra, stability, photothermal performance and photothermal stability. This nanosystem exhibited a good pH and near infrared (NIR) dual-responsive drug release property. In addition, the obtained BP NS-PAMAM@D OX-HA nanocomposites possessed excellent PTT efficiency both in vitro and in vivo. The in vitro cell experiments suggested that the targeted BP NS-PAMAM@DOX-HA presented greater cytotoxicity and higher cellular uptake efficiency. Tumor xenograft model was established in BALB/C mice. The therapeutic effect of BP NS-PAMAM@DOX-HA was further augmented under 808 nm laser irradiation, displaying superior antitumor effect in comparison with chemotherapy or PTT alone. Such a biodegradable BP NS-based platform provide new insights for the rational design of PTT-based combinational cancer therapy.