Integrin α 2 β 1 Targeting DGEA-Modified Liposomal Doxorubicin Enhances Antitumor Efficacy against Breast Cancer

Published on Jun 16, 2021in Molecular Pharmaceutics4.321
· DOI :10.1021/ACS.MOLPHARMACEUT.1C00132
Bingjie Zhou2
Estimated H-index: 2
(Sichuan University),
Min Li (Sichuan University)+ 10 AuthorsShiqi Huang4
Estimated H-index: 4
(Sichuan University)
Sources
Abstract
Breast cancer was the leading cause of newly diagnosed cases of tumors in 2020, ranking as the second highest cause of female death. Chemotherapy remains the conventional treatment of choice for breast tumors in most clinical cases. However, it is often accompanied by a poor prognosis and severe side effects, resulting from an insufficient accumulation of the drug at tumor sites and an unsystematic distribution of the drug across the body. Inspired by the fact that breast tumor cells overexpress integrin α2β1 on the surface, we designed and constructed an integrin α2β1 targeting DGEA-modified liposomal doxorubicin (DGEA-Lipo-DOX) platform for application in breast cancer therapy. The DGEA-Lipo-DOX was stable with a uniform particle size of 121.1 ± 3.8 nm and satisfactory drug encapsulation. Demonstrated in vitro and in vivo, the constructed platform exhibited improved antitumor ability. The DGEA-Lipo-DOX showed 4-fold enhanced blood circulation and 6-fold increased accumulation of DOX at the tumor sites compared to those of free DOX, resulting in a significantly enhanced antitumor efficacy in tumor-bearing mice. A preliminary safety evaluation suggested that the systemic toxicity of DOX was relieved by DGEA-Lipo delivery. Collectively, binding integrin α2β1 by DGEA may represent an alternative therapeutic strategy for potentially safer breast cancer treatment.
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