Citation: Yihan Zhou, Duo Gao, Yaying Wang, Li Liang, Qingyu Zhang, Wenwen Han, Jie Wang, Chunliu Zhu, Xinxin Zhang, Yong Gan. Worm-like micelles facilitate the intestinal mucus diffusion and drug accumulation for enhancing colorectal cancer therapy[J]. Chinese Chemical Letters, ;2024, 35(6): 108967. doi: 10.1016/j.cclet.2023.108967 shu

Worm-like micelles facilitate the intestinal mucus diffusion and drug accumulation for enhancing colorectal cancer therapy

Yihan Zhou ^{a, b} ,
Duo Gao ^{a, c} ,
Yaying Wang ^{a, c} ,
Li Liang ^b ,
Qingyu Zhang ^b ,
Wenwen Han ^b ,
Jie Wang ^{a, e} ,
Chunliu Zhu ^{a, *,} ,
Xinxin Zhang ^{a, b, c, *,} ,
Yong Gan ^{a, b, c, d, *,}

a.
State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
b.
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China
c.
University of Chinese Academy of Sciences, Beijing 100049, China
d.
NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients, National Institutes for Food and Drug Control, Beijing 100050, China
e.
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

chunliuzhu@simm.ac.cn

xinxinzhang@simm.ac.cn

ygan@simm.ac.cn

Received Date: 11 July 2023
Revised Date: 18 August 2023
Accepted Date: 24 August 2023
Available Online: 27 August 2023

Figures(4)

Local delivery of nanoparticles holds promise for colorectal cancer (CRC) therapy. However, the presence of the mucus layer on the epithelium poses a significant challenge to drug delivery, thereby adversely affecting treatment efficiency. It is crucial to develop efficient drug delivery carriers that can effectively overcome mucus barriers to treat colorectal cancer. Herein, we utilized poly(1,4-butadiene)-b-poly(ethylene oxide) polymers to prepare four distinct geometries of polymeric micelles, namely linear micelles (LMs), worm-like micelles (WLMs), large spherical micelles (LSMs), and small spherical micelles (SSMs) to investigate the influence of shape effects on overcoming colonic mucosal barrier. We found that the carriers exhibited diverse shapes while maintaining comparable physicochemical properties. Of these, WLMs had an aspect ratio similar to segmented filamentous bacteria, which exhibited superior mucus penetration ability, leading to prolonged drug release kinetics and faster entry into epithelial cells compared to LSMs. Furthermore, rectally administrated 10-hydroxycamptothecin-loaded WLMs traversed the colorectal mucus in orthotopic CRC nude mice model, penetrated and accumulated within tumor tissue, and effectively aggregated within cancer cells, thereby inducing significantly robust antitumor outcomes in vivo. These findings underscore the significance of shape design in overcoming colonic mucosal absorption barriers, offering a novel approach for the development of drug delivery carriers tailored for effective tumor therapy.
- Worm-like micelles,
- Mucus penetration,
- Shape dependent,
- Transmucosal delivery,
- Colorectal cancer
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