Journal
BIOMACROMOLECULES
Volume 18, Issue 12, Pages 4341-4348Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.7b01374
Keywords
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Funding
- National Natural Science Foundation of China [NSFC 51773199, 51622307, 51390484, 51520105004]
- Youth Innovation Promotion Association CAS
- Sloan Research Fellowship
- Scientific Development Program of Jilin Province [20170520126JH, 20150311069YY]
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In this study, a type of novel thermosensitive polypeptide-based hydrogel with tunable gelation behavior through changing the content of carboxyl groups was developed for the purpose of improving the cisplatin (CDDP) release behavior and enhancing the localized antitumor efficiency. The introduction of carboxyl groups in methoxy-poly(ethylene glycol)-b-(poly(y-ethyl-L-glutamate-co-L-glutamic acid) (mPEG-b-P(ELG-co-LG)) not only led to adjustable mechanical properties of the hydrogel but also significantly reduced the burst release of the drug through the complexation between the carboxyl groups of polypeptide and CDDP. Furthermore, both the good biocompatibility and the biodegradable properties of mPEG-b-P(ELG-co-LG) hydrogel were observed in vivo. Interestingly, the CDDP-complexed mPEG-b-P(ELG-co-LG) hydrogel exhibited significantly enhanced antitumor efficacy in vivo compared to the mPEG-b-PELG hydrogel loaded with CDDP without complexation, although a lower cytotoxicity and IC50 of the CDDP-complexed hydrogel was observed in vitro. Overall, the new type of injectable CDDP-complexed hydrogel may serve as an efficient platform for sustained CDDP delivery in localized tumor therapy.
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