Enhanced in vitro therapeutic efficacy of triphenyltin (IV) loaded vitamin E TPGS against breast cancer therapy

Triphenyltin (Ph3SnL (IV) is a synthetic hydrophobic compound functionalized with a diazo and amino group having potentials to use in anticancer chemotherapy, but its hydrophobic property hindrance the therapeutic efficacy for wider use against cancer treatment. Therefore, in our present work we aimed to develop TPGS micelles loaded with Ph3SnL (IV) to enhanced the therapeutic efficacy in breast cancer cells as compare to docetaxel. Solvent casting method was employed to develop TPGS-Ph3SnL1 (IV), TPGS-Ph3SnL5 (IV) and TPGS-DTX micelles to increase the aqueous solubility of hydrophobic drugs. The size of TPGS-Ph3SnL1 (TSD-30-F) and TPGS-Ph3SnL5 (TSD-34-F) micelles were initially evaluated by dynamic light scattering which were found to be below 50 nm. The morphological characteristics of micelles were observed by TEM, SEM and AFM respectively. Further, drug encapsulation and in vitro drug release profiles of micelles were assessed using dialysis bag diffusion technique under sink condition at pH7.4 at 37 °C over 72 h and analysed through UV–visible spectrophotometry. The anticancer efficacy of TSD-30-F, TSD-34-F and DTX-F were tested against two breast cancer cell lines (MCF-7 and MDA-MB-231) and cervical cancer cell line (HeLa) by MTT assay. IC50 values of TSD-30-F and TSD-34-F displayed very high activity towards breast cancer cells as compared to DTX-F, while moderate in case of HeLa cells. Acridine orange/ethidium bromide as well as flow cytometry observation delineates that micelles induced apoptotic mode of cell death after elevating intracellular reactive oxygen level. Higher cellular uptake of micelles in breast cancer cells was evaluated through TPGS-coumarin6 as compared to coumarin6 without TPGS. Therefore, our study suggests that TPGS micelles may increase therapeutics efficacy of Ph3SnL (IV) in breast cancer cells and can be a promising candidate for targeted drug delivery against breast cancer cells.