Issue 21, 2021

Therapeutic effects of boronate ester cross-linked injectable hydrogels for the treatment of hepatocellular carcinoma

Abstract

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(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-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.

Graphical abstract: Therapeutic effects of boronate ester cross-linked injectable hydrogels for the treatment of hepatocellular carcinoma

Article information

Article type
Paper
Submitted
06 Jun 2021
Accepted
06 Sep 2021
First published
09 Sep 2021

Biomater. Sci., 2021,9, 7275-7286

Therapeutic effects of boronate ester cross-linked injectable hydrogels for the treatment of hepatocellular carcinoma

J. M. Jung, S. H. Kim, V. H. Giang Phan, T. Thambi and D. S. Lee, Biomater. Sci., 2021, 9, 7275 DOI: 10.1039/D1BM00881A

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