Highly Augmented Drug Loading and Stability of Micellar Nanocomplexes Composed of Doxorubicin and Poly(ethylene glycol)-Green Tea Catechin Conjugate for Cancer Therapy

Advanced Materials
Kun LiangMotoichi Kurisawa

Abstract

Low drug loading and instability in blood circulation are two key challenges that impede the successful clinical translation of nanomedicine, as they result in only marginal therapeutic efficacy and toxic side effects associated with premature drug leakage, respectively. Herein, highly stable and ultrahigh drug loading micellar nanocomplexes (MNCs) based on the self-assembly of the anticancer drug doxorubicin (DOX) and a poly(ethylene glycol)-epigallocatechin-3-O-gallate (EGCG) conjugate are developed. The formation of these MNCs is facilitated by strong favorable intermolecular interactions between the structurally similar aromatic EGCG and DOX molecules, which impart exceptionally high drug-loading capability of up to 88% and excellent thermodynamic and kinetic stability. Unlike two clinical formulations of DOX-free DOX and liposomal DOX, which are not effective below their lethal dosages, these DOX-loaded MNCs demonstrate significant tumor growth inhibition in vivo on a human liver cancer xenograft mouse model with minimal unwanted toxicity. Overall, these MNCs can represent a safe and effective strategy to deliver DOX for cancer therapy.

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Citations

Mar 15, 2019·Critical Reviews in Food Science and Nutrition·Xiao-Yu XuHua-Bin Li
Nov 26, 2019·Angewandte Chemie·Qi-Zhi ZhongFrank Caruso
Feb 18, 2021·Chemical Society Reviews·Di WuJesse V Jokerst
Mar 2, 2021·Materials Science & Engineering. C, Materials for Biological Applications·Chao XinZhenyu Wang
Jun 12, 2021·Chemistry, an Asian Journal·Fang WangJianping Lei
Jun 23, 2020·Accounts of Chemical Research·Jiajing ZhouFrank Caruso
Jan 16, 2021·ACS Biomaterials Science & Engineering·Lisa FortuinBert Klumperman
Oct 5, 2021·Critical Reviews in Food Science and Nutrition·Ramkumar SamynathanJosé M Lorenzo

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