NIR-Responsive Black Phosphorus Nanosheet-Integrated Niosomes for Combinatorial Chemo-phototherapy of Cancers.

Cancer remains one of the major challenges in the field of clinical biomedicine. There is a great deal of scope for the development of various innovative therapies. To advance in the field of cancer therapeutics, the research trend has gradually shifted to the development of biocompatible, controlled, and stable carrier systems. To address such issues, herein, we report NIR-responsive black phosphorus (BP) nanosheet-integrated niosomes to mediate chemo-phototherapy of cancers. Niosome-coated black phosphorus nanosheets loaded with indocyanine green (ICG) and doxorubicin (DOX) (NBID) exhibit very high drug loading efficiency (>90%). Upon 808 nm NIR light irradiation, the NBID system initiates combinatorial effects where heat generation induced from BP nanosheets and ICG disrupts the niosomal coating, facilitating the controlled release of ICG and DOX in a pH- and light dual-responsive manner. This combinatorial approach induces DNA damage in cancer cells via DOX and also triggers photothermal (PTT) and photodynamic (PDT) effects, significantly enhancing tumor eradication. In a 2D cell culture model, the NBID formulation demonstrates excellent cytocompatibility in the dark, effective tumor cell uptake, and tumor cell death, showing potential for further application. To mimic the cancer microenvironment even more closely, the NBID nanoformulation has been tested against the 3D tumor spheroids, where NBID formulation shows tumor uptake and causes cancer cell death. The therapeutic efficacy of the NBID system can be controlled by laser, proving its light-responsive behavior to kill cancer cells in vitro. This integrated approach using NBID as a potent platform for combinatorial cancer therapy offers a promising advancement in achieving a safer, controlled, and stable drug delivery system.