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 language | English |
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Article number | 4418 |
Journal | Polymers |
Volume | 13 |
Issue number | 24 |
DOIs | |
State | Published - 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