Cytotoxicity of Novel Redox Sensitive PEG(2000)-S-S-PTX Micelles against Drug-Resistant Ovarian and Breast Cancer Cells

摘要

PurposeSince the last decade, it is established that nonspecific delivery of chemotherapeutics fails to effectively treat cancer due to systemic cytotoxicity, poor biodistribution at tumor site and most importantly the development of drug resistance (MDR). Stimuli-sensitive drug delivery systems gained significant attention in recent years for effective tumor therapy and reversal of MDR. The aim of this study was developing a redox sensitive micellar prodrug system, by taking the advantage of the significant difference in GSH levels between extracellular and intracellular environments, but more importantly in healthy and tumor tissues.MethodsRedox sensitive PEG(2000)-S-S-PTX micelles were developed for intracellular paclitaxel delivery and characterized in vitro. In vitro release studies were carried out and followed by cytotoxicity studies in chemo-resistant ovarian and breast cancer cells in various reducing environments for different time periods to confirm their potential.ResultsPEG(2000)-S-S-PTX, was synthesized and characterized as a redox sensitive micellar prodrug system. The reduction sensitivity and in vitro PTX release properties were confirmed in reducing environments comparatively with physiological conditions. Cytotoxicity studies suggested that ovarian (SK-OV-3) cells could be better candidates for treatment with redox-sensitive drug delivery systems than breast (MCF-7) cancer cells.ConclusionsThe results of this study highlights the importance of personalized therapy since no fits-for-all system can be developed for different cancer with significantly different metabolic activities. Schematic representation of self-assembly of reduction-sensitive PEG2000-S-S-PTX micelles and GSH dependent release of PTX