IR-775 - Hyptis loaded bioactive nanoparticles for enhanced phyto-photothermal therapy of breast cancer cells.

Photo-responsive therapy is an emerging treatment modality due to its bioimaging and therapeutic properties. Phototherapy induces localized hyperthermia and selectively eradicates cancer cells. The current study showed that multifunctional biodegradable liposome nanosystem (HIL NPs) containing Hyptis suaveolens bioactive molecules and IR-775, a NIR dye showed efficient bioavailability to cancer ells and allowed tumor ablation upon NIR laser irradiation. The resulting entities present in the nanosystem, i.e., bioactive molecules of Hyptis, serve as an anticancer agent, and IR-775 helps in the photothermal ablation of highly metastatic breast cancer cells. Hyptis suaveolens is a weed that grows rampantly, impeding the growth of neighboring plants; nonetheless, its bioactive compounds have demonstrated therapeutic benefits. The obtained HIL NPs, photothermally active liposome nanosystem showed a high fluorescence absorption peak in the NIR range and delivered a photothermal conversion efficiency of 55.20 % upon NIR laser irradiation. TEM and particle size analyzer revealed that HIL NPs have a size of 141 ± 30 nm with a spherical shape. The results of in-ovo (zebrafish) experiments have shown efficient bioimaging capabilities with minimal concentrations of HIL NPs compared to respective controls. Furthermore, in-vitro studies of HIL NPs against triple-negative breast cancer (4T1) indicated effective anticancer activity by a combined cytotoxic effect and hyperthermia. Tumor ablation was facilitated by reactive oxygen species production and hyperthermia, leading to DNA damage and apoptosis due to overexpression of É£-H2AX, Cathepsin B, and p53, which halted cancer cell proliferation. Therefore, HIL NPs demonstrated effective anticancer effects induced by combined phyto-photothermal therapy when evaluated against an in-vitro breast cancer model.

PLGA nanoparticle loaded with antioxidants and photosensitizer for ROS shock mediated phototherapy of triple negative breast cancer.

The potential use of antioxidants for photodynamic therapy (PDT) is investigated in this study. PDT causes reactive oxygen species (ROS)-mediated cell death; on the contrary, antioxidants scavenge ROS. The use of a photosensitizer along with an antioxidant photosensitizer compensates for the loss of ROS due to the use of antioxidant, eventually leading to cell death. In this work, for PDT and photothermal therapy (PTT), we have combined the photosensitizer IR 792 perchlorate dye with the antioxidants alpha-tocopherol (A) andp-coumaric acid (C) encapsulated in a polymeric nanocarrier (AC IR NPs). We have reported the synthesis of AC IR NPs using poly lactic-co-glycolic acid (PLGA) by nanoprecipitation method. The size of the polymeric nanoparticles was found to be 80.4 ± 15.6 nm, with a spherical morphology observed by scanning electron microscopy and transmission electron microscopy. The synthesized AC IR NPs demonstrated good biocompatibility in fibroblast cell lines (L929). Furthermore, the efficacy assessment of the as prepared nanosystemin vitroon breast cancer cell lines (4T1) revealed a significant cell death of nearly 80%. This could be attributed to the ROS generation leading to oxidative stress and inhibition of metastasis. This study provides evidence that the combination of antioxidant drugs along with photosensitizers have the potential to be an effective therapy for treating triple negative breast cancer.

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 γ-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.