Light- and Redox-Responsive Block Copolymers of mPEG-SS-ONBMA as a Smart Drug Delivery Carrier for Cancer Therapy

Abstract

The development of stimuli-responsive polymeric micelles for targeted drug delivery has attracted much research interest in improving therapeutic outcomes. This study designs copolymers responsive to ultraviolet (UV) light and glutathione (GSH). A disulfide linkage is positioned between a hydrophilic poly(ethylene glycol) monomethyl ether (mPEG) and a hydrophobic o-nitrobenzyl methacrylate (ONBMA) to yield amphiphilic copolymers termed mPEG-SS-pONBMA. Three copolymers with different ONBMA lengths are synthesized and formulated into micelles. An increase in particle size and a decrease in critical micelle concentration go together with increasing ONBMA lengths. The ONB cleavage from mPEG-SS-pONBMA-formed micelles results in the transformation of hydrophobic cores into hydrophilic ones, accelerating drug release from the micelles. Obvious changes in morphology and molecular weight of micelles upon combinational treatments account for the dual-stimuli responsive property. Enhancement of a cell-killing effect is clearly observed in doxorubicin (DOX)-loaded micelles containing disulfide bonds compared with those containing dicarbon bonds upon UV light irradiation. Collectedly, the dual-stimuli-responsive mPEG-SS-pONBMA micelle is a better drug delivery carrier than the single-stimuli-responsive mPEG-CC-pONBMA micelle. After HT1080 cells were treated with the DOX-loaded micelles, the high expression levels of RIP-1 and MLKL indicate that the mechanism involved in cell death is mainly via the DOX-induced necroptosis pathway.

Efficacy tumor therapeutic applications of stimuli-responsive block copolymer-based nano-assemblies

“…ROS-responsive functional groups introduced into block copolymers include thiol-ketone (TK), polysulfide, boronic acid ester [ 15 ], anthocyanin, hoof, and ferrocene [ [16] , [17] , [18] ]. GSH-responsive chemical bonds include disulfide bonds [ [19] , [20] , [21] ], thioether bonds, diselenide bonds [ 22 ], selenium ether bonds [ 23 , 24 ], sulfur-ketone bonds [ 25 , 26 ], and succinimide-thioether bonds [ 27 ]. The block copolymers-based nano-assemblies undergo structure changes upon exposure to redox, delivering drugs rapidly and efficiently in specific tumor sites.…”

Amphibian-Derived Natural Anticancer Peptides and Proteins: Mechanism of Action, Application Strategies, and Prospects

“…This finding effectively addresses the issue of apoptosis escape without requiring additional treatment [ 84 ]. The necrosome, which consists of RIPK1, RIPK3, and MLKL, is the primary executor and defining characteristic of necrosis [ 85 ]. Research indicates that partially attenuated necrosis induced by Bufalin can be achieved through the knockout of TNFR1 and RIPK1 genes.…”