Reactive oxygen species-responsive miktoarm amphiphile for triggered intracellular release of anti-cancer therapeutics

Hyun Chul Kim, Eunjoo Kim, Se Guen Lee, Sung Jun Lee, Sang Won Jeong, Young Jae Lee, Mi Kyung Kwon, Seong Kyoon Choi, Jun Seong Hwang, Eunsook Choi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Reactive oxygen species (ROS)-responsive nanocarriers have received considerable research attention as putative cancer treatments because their tumor cell targets have high ROS levels. Here, we synthesized a miktoarm amphiphile of dithioketal-linked ditocopheryl polyethylene glycol (DTTP) by introducing ROS-cleavable thioketal groups as linkers between the hydrophilic and hydrophobic moieties. We used the product as a carrier for the controlled release of doxorubicin (DOX). DTTP has a critical micelle concentration (CMC) as low as 1.55 µg/mL (4.18 × 10−4 mM), encapsulation efficiency as high as 43.6 ± 0.23% and 14.6 nm particle size. The DTTP micelles were very responsive to ROS and released their DOX loads in a controlled manner. The tocopheryl derivates linked to DTTP generated ROS and added to the intracellular ROS in MCF-7 cancer cells but not in HEK-293 normal cells. In vitro cytotoxicity assays demonstrated that DOX-encapsulated DTTP micelles displayed strong antitumor activity but only slightly increased apoptosis in normal cells. This ROS-triggered, self-accelerating drug release device has high therapeutic efficacy and could be a practical new strategy for the clinical application of ROS-responsive drug delivery systems.

Original languageEnglish
Article number4418
JournalPolymers
Volume13
Issue number24
DOIs
StatePublished - 1 Dec 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Drug delivery system
  • Miktoarm amphiphile
  • ROS-responsive
  • Tocopheryl derivate
  • Tumor therapy

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