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Folate-PEG-PROTAC Micelles for Enhancing Tumor-Specific Targeting Proteolysis In Vivo.
Advanced Healthcare Materials 2024 April 28
Proteolysis targeting chimeras (PROTACs) technology has been rapidly developed as a novel and selective medicinal strategy for the degradation of cellular proteins in cancer therapy. However, the applications of PROTACs as the heterobifunctional molecules are largely limited by high molecular weight, low bioavailability, poor permeability, insufficient targeting and low efficacy in vivo. Herein, self-assembling micelles of FA-PEG-PROTAC are designed for cancer cell selective targeting and reductive-response proteolysis in tumor-bearing mice. FA-PEG-PROTAC are prepared by conjugating folic acid (FA)-PEG with EGFR-targeting PROTAC (PRO) via a disulfide bond. The FA-PEG-PROTAC micelles, formed by self-assembling, is demonstrated to significantly improve tumor targeting efficacy and exhibit excellent anti-tumor efficacy in mouse xenograft model compared to the traditional PROTACs. The strategy of applying self-assembled FA-PEG-PROTAC micelles in tumor therapy can not only improve targeted proteolysis efficiency but broaden applications in the development of PROTAC-based drugs. This article is protected by copyright. All rights reserved.
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