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Integrated Multifunctional Micelles Co‐Self‐Assembled from Polypeptides Conjugated with Natural Ferulic Acid and Lipoic Acid for Doxorubicin Delivery
Author(s) -
Chen Tao,
Qiu Min,
Zhang Jian,
Sun Huanli,
Deng Chao,
Zhong Zhiyuan
Publication year - 2018
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.201701367
Subject(s) - doxorubicin , chemistry , micelle , nanocarriers , lipoic acid , nanomedicine , cardiotoxicity , pharmacology , drug delivery , pharmaceutics , ferulic acid , ethylene glycol , biochemistry , nanoparticle , materials science , nanotechnology , toxicity , chemotherapy , antioxidant , medicine , organic chemistry , surgery , aqueous solution
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 α v β 3 ‐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.