期刊
BIOMATERIALS SCIENCE
卷 9, 期 21, 页码 7275-7286出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1bm00881a
关键词
-
资金
- National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF-2020R1I1A1A01075103, NRF-2017R1D1A1B03028061]
A thermo-responsive hydrogel was developed for targeted delivery of drugs to tumor tissues, showing stable formation in vivo and potential for suppressing tumor growth. This study suggests that the pH-responsive drug-releasing hydrogel has great promise for localized anticancer therapy.
Hepatocellular carcinoma is the most common malignancy with a high incidence rate and is the leading cause of cancer-related deaths. Herein, we developed a thermo-responsive hydrogel comprising poly(epsilon-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(epsilon-caprolactone-co-lactide (PCLA) that exhibits acidity-accelerated delivery of the tumor-targeting glucuronic acid-bearing doxorubicin (DOX-pH-GA) conjugate into tumor tissues. The PCLA copolymer was post-modified with boronic acid (BA-PCLA) to covalently cross-link with the pH-responsive DOX-pH-GA conjugate. The BA-PCLA copolymer effectively coordinated with the DOX-pH-GA conjugate through the boronate ester formation and showed a lower critical gelation temperature. The DOX conjugated via boronate ester exhibited a sustained release in vitro. Subcutaneous administration of PCLA copolymers formed in situ gels in the subcutaneous layers of Sprague-Dawley rats and degraded after 6 weeks. Similarly, BA-PCLA copolymers coordinated with DOX-pH-GA formed a stable in situ gel in vivo. In vivo imaging studies demonstrated that DOX-pH-GA was released in a sustained manner. The anti-tumor activity of the DOX releasing injectable hydrogel was examined using a HepG2 liver cancer xenograft model. The in vivo antitumor effect demonstrated that the DOX releasing hydrogel depot remarkably suppresses the tumor growth. These results demonstrate that the pH-responsive DOX releasing thermo-responsive hydrogel depot has great potential for application in localized anticancer therapy.
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