Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Intracellular Delivery of Anticancer Agents Using Dual Responsive Nanomicelles Synthesized Via Raft Polymerization Publisher



Esmaeili M1 ; Shahbaz S1, 2 ; Kamankesh M3 ; Shahin M4 ; Mirzazadeh Tekie FS1 ; Fadavi P4 ; Beigi M5 ; Mortazavi SA6 ; Dinarvand R1, 2, 7
Authors
Show Affiliations
Authors Affiliations
  1. 1. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmaceutical Nanotechnology, Faculty of pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Polymer Laboratory, School of Chemistry, College of Science, University of Tehran, Tehran, Iran
  4. 4. Department of Radiation Oncology, School of Medicine, Iran University of Medical Science, Tehran, Iran
  5. 5. Shohadaye Haftom-e-Tir Hospital, Iran University of Medical Sciences, Tehran, Iran
  6. 6. Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  7. 7. Leicester School of Pharmacy, Leicester Institute for Pharmaceutical Innovation, De Montfort University, Leicester, United Kingdom

Source: European Polymer Journal Published:2023


Abstract

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 < 0.05). The combination of X-ray irradiation (2 Gy) and DTX release exhibited the highest cytotoxicity on MCF-7 cells (IC50 = 0.019 µg/ml). Overall, the nanomicelles prepared in this study, in combination with X-ray irradiation, demonstrated enhanced antitumor efficacy of the system. © 2023 Elsevier Ltd
Related Docs
1. Smart Internal Stimulus-Responsive Nanocarriers for Drug and Gene Delivery, Smart internal stimulus-responsive nanocarriers for drug and gene delivery (2015)