Mitochondrial Dysfunction–Induced Apoptosis in Breast Carcinoma Cells Through pH-Dependent Intracellular Quercetin NDDS of PVPylated-TiO2NPs

Abstract

Background: The conventional chemotherapy has some noticeable drawbacks, such as lack of specificity, the requirement of high drug-dose, adverse effects, and gradual development of multidrug resistance (MDR), that reduce the efficacy of cancer therapy. Aim: To achieve intracellular drug delivery, strategies for overcoming various biologic barriers from the system level to the organ level, to the cellular level. To win through over these challenges in chemotherapy is to be achieving high drug loading combination with low leakage at physiologic pH, minimal toxicity toward healthy cells, and tunable controlled release at the site of action is an ongoing challenge. Methods: To assist drug delivery, we have prepared PVPylated-TiO2NPs consisting of Qtn with high loading efficiency (26.6% w/w) for NDDS. Qtn-PVPylated-TiO2NPs uptake via endocytosed by cancer cells able to generate intracellular ROS, to decrease the mitochondrial membrane potential loss (Δψm) to release cytochrome- c, Bcl-2 dysregulation into the cytosol and then activating caspase-3 to induce cancer cell apoptosis. Results: These novel nanocombinations can be used to improve cancer nanotherapy by induction of apoptosis in vitro. Analysis at molecular level revealed that Qtn-PVPylated-TiO2NPs nanocombination induced Δψm-mediated apoptotic signaling pathway. Conclusion: To our knowledge, this is a novel report using Qtn-PVPylated-TiO2NPs nanocombinations to study the pH-dependent intracellular NDDS to cancer cells. This new nanoformulations of this study may further advance the use of Qtn-PVPylated-TiO2NPs based nanotherapeutic of biomaterials for various biomedical applications, especially cancer nanotherapy.