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  • Title: Integrated Multifunctional Micelles Co-Self-Assembled from Polypeptides Conjugated with Natural Ferulic Acid and Lipoic Acid for Doxorubicin Delivery.
    Author: Chen T, Qiu M, Zhang J, Sun H, Deng C, Zhong Z.
    Journal: Chemphyschem; 2018 Aug 17; 19(16):2070-2077. PubMed ID: 29316094.
    Abstract:
    The development of safe, easily accessible, and multifunctional nanocarriers is a big topic in nanomedicine research. Here, integrated multifunctional micelles (IMM) were developed by co-self-assembly of poly(ethylene glycol)-b-poly(l-lysine) derivatives with natural ferulic acid (FA) or lipoic acid (LA). FA confers IMM with intrinsic antitumor activity, improved loading of doxorubicin (DOX) through π-π stacking, and reduced DOX cardiotoxicity. LA provides IMM with reversible crosslinking property, which leads to a high colloidal stability with inhibited drug leakage and triggered intracellular DOX release. Notably, our results showed that cRGD-decorated IMM (cRGD-IMM) had a small size (≈56 nm) and superior loading of DOX (27.1 wt. %). Blank cRGD-IMM, though nontoxic to normal cells, exhibited obvious antiproliferative activity against cancer cells including B16F10 and HCT-116 cells at 150 μg FA equiv. mL-1 . DOX-loaded cRGD-IMM displayed enhanced growth inhibition of αv β3 -positive B16F10 and HCT-116 cells, a long elimination half-life of 3.85 h, and a high maximum-tolerated dose of over 100 mg DOX equiv. kg-1 . Histological analysis revealed that DOX-loaded cRGD-IMM at 100 mg DOX equiv. kg-1 caused negligible cardiotoxicity, which is a major issue for the clinical use of DOX. These integrated multifunctional micelles with excellent safety and accessibility have emerged as a new platform for targeted cancer chemotherapy.
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