Transferrin conjugated pH/NIR-responsive black phosphorus nanoplatform: A novel multimodal approach for breast cancer...

Cancer is one of the foremost causes of death, posing a significant challenge to global health. Breast cancer is predominant cancer type in women globally. Nanotheranostic platforms have emerged as a promising strategy for enhancing breast cancer therapy by integrating both diagnostic and therapeutic functionalities. Black phosphorous nanosheets (BPNSs) are nanotheranostic 2D materials that can adsorb a large number as well as quantity of therapeutic or theranostic agents due to their greater surface area. Herein, the authors developed an efficient pH and NIR-responsive nanotheranostic drug delivery platform for synergistic chemo/photothermal/photodynamic therapy of breast cancer. The exfoliated BPNSs were surface loaded with an anticancer drug, doxorubicin (DOX), functionalized with a photo-responsive polymer, polydopamine (PDA), and conjugated with a protein-based ligand, transferrin (TF). The prepared BP-based nanoformulation demonstrated excellent photothermal stability, improved targeting efficiency and desired therapeutic activity. A pH/NIR-responsive nature was observed during in vitro DOX release studies with negligible toxicity during hemolysis and CAM assay. Cell line studies on 4 T1 cells showed NIR-specific toxicity compared to non-irradiated groups with excellent ligand-mediated cellular uptake. Furthermore, an increase in the amount of necrotic and apoptotic cells in 4 T1 cells with elevated ROS levels were observed. 4 T1-tumour bearing BALB/c mice models administered with BP-based nanoformulation indicated an efficient reduction in tumour volume in NIR-irradiated groups and enhanced pharmacokinetic parameters. In vitro and in vivo studies demonstrated that the synergistic approach of merging chemotherapy with photothermal and photodynamic therapy exhibits remarkable antitumour effectiveness, excellent biocompatibility, and promising competence for clinical application.