Intracellular delivery of anticancer agents using dual responsive nanomicelles synthesized via RAFT polymerization

[Display omitted] •Diselenide core crosslinked micelles were developed for docetaxel (DTX) delivery, combining synergistic antitumor chemotherapy with radiotherapy.•DTX-loaded nanomicelles displayed increased cytotoxicity and apoptosis, enhancing antitumor efficacy.•The micelles demonstrated dual-responsive controlled release profiles in response to intracellular glutathione concentration and X-ray exposure, showing potential for targeted chemotherapy delivery.•A combination of X-ray irradiation and DTX release from micelles showed higher cytotoxicity on MCF-7 cells than free DTX, indicating potential improvement in chemotherapy effectiveness. In this study, diselenide core crosslinked nanomicelles were developed for the delivery of docetaxel (DTX) to tumor cells, aiming to achieve synergistic antitumor chemotherapy in combination with radiotherapy. The nanomicelles were composed of a random triblock copolymer, Poly(poly(ethylene glycol) methyl ether methacrylate-co-N-isopropylacrylamide-co-Acrylic acid N-hydroxysuccinimide ester), synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, and crosslinked using selenocystamine dihydrochloride. Physicochemical experiments were conducted to characterize the polymer synthesis and nanoparticles. The in vitro release profile was studied in response to redox conditions. In vitro cytotoxicity studies were performed on the breast cancer (MCF-7) cell line. The results showed the formation of 81 ± 5.2 nm spherical nanomicelles with a drug loading and encapsulation efficiency (EE) of 8.09% (w/w) and 97% (w/w), respectively. The nanomicelles exhibited dual responsive controlled release profiles, with approximately 80% of the drug being released within the first 2 h in response to intracellular glutathione (GSH) concentration and X-ray exposure. Fluorescent microscopy confirmed the effective internalization of the nanomicelles. Furthermore, the nanomicelles demonstrated increased cytotoxicity and apoptosis rates. The DTX-loaded nanomicelles exhibited a lower IC50 value (0.037 µg/ml) compared to free DTX (0.092 µg/ml) (P