Terminalia chebula Polyphenol and Near-Infrared Dye-Loaded Poly(lactic acid) Nanoparticles for Imaging and Photothermal Therapy of Cancer Cells

Photothermal/photodynamic therapies (PTT/ PDT) are multimodal approaches employing near-infrared (NIR) light-responsive photosensitizers for cancer treatment. In the current study, IR-775, a hydrophobic photosensitizer, was used in combination with a polyphenols (p)-rich ethyl acetate extract from Terminalia chebula to treat cancer. IR-775 dye and polyphenols were encapsulated in a poly(lactic acid) polymeric nanosystem (PpIR NPs) to increase the cell bioavailability. The hydrodynamic diameter of PpIR NPs is 142.6 +/- 2 nm and exhibited physical stability. The nanosystem showed enhanced cellular uptake in a lung cancer cell line (A549). Cell cytotoxicity results indicate that PpIR NPs showed more than 82.46 +/- 3% cell death upon NIR light treatment compared to the control groups. Both PDT and PTT generate reactive oxygen species (ROS) and cause hyperthermia, thereby enhancing cancer cell death. Qualitative and quantitative analyses have depicted that PpIR NPs with NIR light irradiation have decreased protein expression of HSP70 and PARP, and increased gamma-H2AX, which collectively lead to cell death. After NIR light irradiation, the relative gene expression patterns of HSP70 and CDK2Na were also downregulated. Further, PpIR NPs uptake has been studied in 3D cells and in ovo bioimaging in zebrafish models. In conclusion, the PpIR NPs show good cancer cell cytotoxicity and present a potential nanosystem for bioimaging.