ROS-responsive nano-medicine for navigating autophagy to enhance targeted therapy of inflammatory bowel disease

You Chen; Juewen Feng; Yang Chen; Chuanhe Xia; Min Yao; Wenxing Ding; Xiang Li; Xiuzhi Fu; Shulei Zheng; Yin Ma; Jiafeng Zou; Minbo Lan; Feng Gao

doi:10.1016/j.ijpharm.2024.124117

ROS-responsive nano-medicine for navigating autophagy to enhance targeted therapy of inflammatory bowel disease

Int J Pharm. 2024 Apr 12:124117. doi: 10.1016/j.ijpharm.2024.124117. Online ahead of print.

Authors

You Chen¹, Juewen Feng¹, Yang Chen¹, Chuanhe Xia¹, Min Yao¹, Wenxing Ding¹, Xiang Li¹, Xiuzhi Fu¹, Shulei Zheng¹, Yin Ma¹, Jiafeng Zou², Minbo Lan³, Feng Gao⁴

Affiliations

¹ Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
² Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, China; Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, China; Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai 200237, China.
³ Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, China.
⁴ Shanghai Frontier Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, China; Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, China; Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, Shanghai 200237, China; Optogenetics and Synthetic Biology Interdisciplinary Research Center, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China; Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, East China University of Science and Technology, Shanghai 200237, China. Electronic address: fgao@ecust.edu.cn.

PMID: 38615805
DOI: 10.1016/j.ijpharm.2024.124117

Abstract

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder characterized by immune dysregulation and intestinal inflammation. Rapamycin (Ra), an mTORC1 pathway inhibitor, has shown promise for autophagy induction in IBD therapy but is associated with off-target effects and toxicity. To address these issues, we developed an oral liposome responsive to reactive oxygen species (ROS) using lipids and amphiphilic materials. We combined ketone thiol (TK) for ROS responsive and hyaluronic acid (HA) with high affinity for CD44 receptors to prepare rapamycin-loaded nanoparticle (Ra@TH). Owing to its ROS responsive characteristic, Ra@TH can achieve inflammatory colonic targeting. Additionally, Ra@TH can induce autophagy by inhibiting the mTORC1 pathway, leading to the clearance of damaged organelles, pathogenic microorganisms and oxidative stress products. Simultaneously, it also collaboratively inhibits the NF-κB pathway suppressed by the removal of ROS resulting from TK cleavage, thereby mediating the expression of inflammatory factors. Furthermore, Ra@TH enhances the expression of typical tight junction proteins, synergistically restoring intestinal barrier function. Our research not only expands the understanding of autophagy in IBD treatment but also introduces a promising therapeutic approach for IBD patients.

Keywords: Colonic targeting; Inflammatory bowel disease; Navigating autophagy; ROS-responsive; Rapamycin.