Integrated Multifunctional Micelles Co-Self-Assembled from Polypeptides Conjugated with Natural Ferulic Acid and Lipoic Acid for Doxorubicin Delivery

Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry
Tao ChenZhiyuan Zhong

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,...Continue Reading

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Citations

Jan 18, 2019·Pharmaceutical Development and Technology·Nussana ThitichaiNorased Nasongkla
Nov 3, 2020·Advanced Drug Delivery Reviews·Chao DengZhiyuan Zhong
Jul 4, 2021·Biomaterials·Xu WangJianjun Cheng
Oct 30, 2019·Biomacromolecules·Huanli SunChao Deng

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