Journal of Industrial and Engineering Chemistry, Vol.109, 359-371, May, 2022
Tunable paclitaxel release carrier using diselenide-disulfide balance as regulator
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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-alt- DSeDP-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.
Keywords:Diselenide-disulfide balance;Redox responsiveness;Thermal responsiveness;Nanomicellar complex;Tunable PTX release
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