Plug-and-Play Nanorization of Coarse Black Phosphorus for Targeted Chemo-photoimmunotherapy of Colorectal Cancer.

Because of their extraordinary physical properties and biocompatibility, black phosphorus (BP) nanosheets (NSs) have been intensively employed in chemo-phototherapies, such as plasmonic inorganic nanoparticles or graphene NSs, over the past few years. However, most biomedical studies using BP NSs are only concerned with the optical property of BP NSs to repeatedly demonstrate chemo-phototherapeutic efficacies, although BP NSs have different properties from inorganic nanoparticles or graphene NSs, such as corrugated crystal structure, hydrophilicity, and biodegradability. Moreover, it is still a challenging issue to efficiently fabricate uniform BP NSs for clinical translation because of the top-down nature of fabrication, despite the easy preparation of coarse BP flakes. It is thus essential to explore their most suitable bioapplications as well as suggest an easy-to-access strategy to produce uniform BP NSs for realization as advanced therapeutic materials. To rationalize these issues, this report introduces a plug-and-play nanorization, ultrasonic bubble bursting, of coarse BP flakes for continuous BP NS production, and the resulting uniform NSs (∼40 nm lateral dimension, ∼0.15 polydispersity index) were used as base materials to load drug (doxorubicin), targeting agent (chitosan-polyethylene glycol), and cancer growth inhibitor (programmed death ligand 1 and small interfering RNA) for achieving efficacious chemo-photoimmunotherapy of colorectal cancer.