Mitochondrial dysfunction-induced apoptosis in breast carcinoma cells through a pH-dependent intracellular quercetin NDDS of PVPylated-TiO2NPs. Issue 21 (18th May 2018)

• Record Type: Journal Article
• Authors: Ponraj, Thondhi; Vivek, Raju; Paulpandi, Manickam; Rejeeth, Chandrababu; Nipun Babu, Varukattu; Vimala, Karuppaiya; Anand, Krishnan; Sivaselvam, Subramani; Vasanthakumar, Alagarsamy; Ponpandian, Nagamony; Kannan, Soundarapandian
• Is Part Of: Journal of materials chemistry. Volume 6:Issue 21(2018)
• Page Start: 3555
• Page End: 3570
• Publication Date: 2018-05-18
• Subjects: Materials -- Periodicals; Chemistry, Analytic -- Periodicals; Biomedical materials -- Research -- Periodicals; 543.0284
• DOI: 10.1039/c8tb00769a
• Languages: English
• ISSNs: 2050-750X

Abstract

Abstract : In this article, we report the validation of cancer nanotherapy for treatment of cancers using quercetin (Qtn). Abstract : In this article, we report the validation of cancer nanotherapy for the treatment of cancers using quercetin (Qtn). Much attention has been paid to the use of nanoparticles (NPs) to deliver drugs of interest in vitro / in vivo. Highly developed NPs-based nano drug delivery systems (NDDS) are an attractive approach to target cancer cell apoptosis, which is related to the onset and progression of cancer. Conventional chemotherapy has some notable drawbacks, such as lack of specificity, requirement of high drug doses, adverse effects, and gradual development of multidrug resistance (MDR), that decrease the efficacy of cancer therapy. To overcome these challenges of chemotherapy, the achievement of high drug loading in combination with low leakage at physiological pH, minimal toxicity toward healthy cells, and tunable controlled release at the site of action is an ongoing challenge. To assist drug delivery, we have prepared PVPylated-TiO2 NPs containing Qtn with high loading efficiency (26.6% w/w) as a NDDS. The Qtn-PVPylated-TiO2 NPs are uptaken via endocytosis by cancer cells and can generate intracellular reactive oxygen species (ROS) in order to increase mitochondrial membrane potential loss (Δψm) and enable release of cytochrome- c, followed by dysregulation of Bcl-2 into the cytosol and activation of caspase-3 to induce cancer cell apoptosis. These novel nanocombinations can be utilized to improve cancer nanotherapy by induction of apoptosis in vitro . Analysis at the molecular level revealed that the Qtn-PVPylated-TiO2 NPs nanocombinations induced Δψm-mediated apoptotic signaling pathways. Overall, this study demonstrated that careful design of non-toxic nanocarriers for cancer nanotherapy can yield affordable NDDS.