Journal
JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY
Volume 109, Issue -, Pages 359-371Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jiec.2022.02.020
Keywords
Diselenide-disulfide balance; Redox responsiveness; Thermal responsiveness; Nanomicellar complex; Tunable PTX release
Funding
- Specialized Scientific Research Fund Projects of Education Department of Shaanxi Province [21JK0530]
- Natural Science Fundamental Research Program of Shaanxi Province [2021JQ-550]
- Shaanxi Province Undergraduate Innovation & Entrepreneurship Training Program [S202110708031]
- Natural Science Research Fund of Shaanxi University of Science and Technology [2019BJ-43]
- Key Research and Development Program of Shaanxi Province [2020SF-423, 2020FP-029]
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A study was conducted to achieve tunable release of paclitaxel (PTX) by fabricating thermal and redox-responsive copolymer nanomicellar assemblies. The release behavior of the nanomicelles was found to be dependent on their structure and assembly ratio, which was validated through cellular uptake and in vivo anti-tumor experiments.
There are many reasons that lead to the failure of cancer chemotherapy, such as uncontrolled drug release, low drug utilization, and severe side effects. To overcome these obstacles, two kinds of thermal and redox-responsive copolymers with multiple diselenide/disulfide linkages, polyethylene glycol -altdiselenodipropionate/disulfhydryldipropionate-b-poly(N-isopropylacrylamide) (abbreviated as PEG-altDSeDP-b-PNIPAM and PEG-alt-DSDP-b-PNIPAM) were fabricated by alternative esterification and following atom transfer radical polymerization. Afterward, these prepared copolymers were mixed in line with the mass ratio of 8:0, 5:3, 3:5, 0:8 (denoted as S1, S2, S3, and S4, respectively), and self-assembled with paclitaxel (PTX) to obtain PTX-loaded S1, S2, S3, and S4 nanomicellar assemblies, aiming to realize PTX tunable release using diselenide-disulfide balance as regulator. The chemical structures of these two copolymers were characterized by gel permeation chromatography, indicating eight diselenide/disulfide linkages and eight PEG units were contained in these copolymers. Moreover, the thermal-responsive property was detected by UV-vis spectroscopy, meanwhile, the redox responsiveness was observed by TEM in the presence of 10 mM glutathione. We found that 76.90% of PTX was released from S1 nanomicelles within 23 h. In contrast, this percentage decreased to 64.53% for S4 nanomicelles even the incubation time prolonged, indicating explosive and slow release behaviors of S1 and S4 nanomicelles, respectively. In addition, gradually decreased fluorescence intensity around the cellular nucleus was occurred from S1 to S4 orderly, which was consistent with cellular uptake and in vivo anti-tumor experiments. Taken together, this work not only provides a strategy for tunable PTX release, but also improves effectiveness of PTX in cancer treatment. (c) 2022 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.
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