A batch-by-batch free route for the continuous production of black phosphorus nanosheets for targeted combination cancer therapy

Although 2D materials such as graphenes, chalcogenides, and black phosphorus (BP) have been intensively studied for a wide range of future technological applications, the multiple harsh reactions and post-treatments required to produce exfoliated nanosheets (NSs) represent challenging barriers to their realization. In the present study, a batch-by-batch free route to produce BP NSs was demonstrated, and the NSs were employed as base materials for the chemo-phototherapy of breast cancer. Specifically, a single-pass catalytic conversion of an all-in-one precursor (red P, Au–Sn, and iodine) in a heated tubular reactor (at a 650 °C wall temperature for 15.5 s) continuously produced crumpled BP NSs, and the NS-laden gas stream was passed through an activated carbon-packed tube to remove the reacted gases. Subsequently, doxorubicin (D), poly-l-lysine (L), and hyaluronic acid (H) were incorporated without further purification of these NSs to form BP-DLH, which was then employed in both in vitro and in vivo chemo-phototherapies. The biocompatibility and near-infrared-induced photothermal activity of BP NSs facilitate targeted delivery to CD44-overexpressing breast cancer cells to assist in the therapeutic efficacy of D. A simple method of synthesizing nanosheets of black phosphorus, demonstrated by researchers in South Korea, could help the development of a therapy that destroys cancer cells. Black phosphorus comprises weakly bound layers of atoms. Nanosheets just a few layers thick are known to be useful in photothermal therapy: the black phosphorus absorbs laser light, gets hot and destroys any nearby cells. Existing methods of synthesizing these nanosheets are time-consuming and require harsh chemicals. Instead, Jeong Hoon Byeon from Yeungnam University, Gyeongsan, and colleagues continuously produced black phosphorus nanosheets by simply heating red phosphorus, an alloy of gold and tin, and iodine. The team demonstrated that injection of these nanosheets under the skin in mice and subsequent illumination with infrared laser light led to tumor regression. A batch-by-batch free route for the continuous production black phosphorus nanosheets in a single-pass gas stream was designed, and the resulting nanosheets were directly employed in targeted chemo-phototherapy upon incorporating with doxorubicin, poly-l-lysine, and hyaluronic acid.