A mesoporous polydopamine-derived nanomedicine for targeted and synergistic treatment of inflammatory bowel disease by pH-Responsive drug release and ROS scavenging

Haidi Guan; Zhongwei Xu; Guangsheng Du; Qinghua Liu; Qianshan Tan; Yihui Chen; Shuaishuai Chen; Jingfeng Wu; Fengchao Wang; Jixi Zhang; Lihua Sun; Weidong Xiao

doi:10.1016/j.mtbio.2023.100610

A mesoporous polydopamine-derived nanomedicine for targeted and synergistic treatment of inflammatory bowel disease by pH-Responsive drug release and ROS scavenging

Mater Today Bio. 2023 Mar 15:19:100610. doi: 10.1016/j.mtbio.2023.100610. eCollection 2023 Apr.

Authors

Haidi Guan¹, Zhongwei Xu¹, Guangsheng Du¹, Qinghua Liu¹, Qianshan Tan¹, Yihui Chen¹, Shuaishuai Chen¹, Jingfeng Wu^{2

3}, Fengchao Wang³, Jixi Zhang⁴, Lihua Sun¹, Weidong Xiao¹

Affiliations

¹ Department of General Surgery, Xinqiao Hospital, Army Medical University, No.183 Xinqiao Road, Chongqing, 400037, China.
² Department of Gastroenterology, Southwest Hospital, Army Medical University, Gaotanyan Street, Shapingba, Chongqing, 400038, China.
³ Institute of Combined Injury of PLA, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Gaotanyan Street, Shapingba, Chongqing, 400038, China.
⁴ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing, 400044, China.

Abstract

Repurposing clinically approved drugs to construct novel nanomedicines is currently a very attractive therapeutic approach. Selective enrichment of anti-inflammatory drugs and reactive oxygen species (ROS) scavenging at the region of inflammation by stimuli-responsive oral nanomedicine is an effective strategy for the treatment of inflammatory bowel disease (IBD). This study reports a novel nanomedicine, which is based on the excellent drug loading and free radical scavenging ability of mesoporous polydopamine nanoparticles (MPDA NPs). By initiating polyacrylic acid（PAA）polymerization on its surface, a "core-shell" structure nano-carrier with pH response is constructed. Then, under alkaline conditions, using the π-π stacking and hydrophobic interaction between the anti-inflammatory drug sulfasalazine (SAP) and MPDA, the nanomedicines (PAA@MPDA-SAP NPs) loaded efficiently (928 μ g mg^-1) of SAP was successfully formed. Our results reveal that PAA@MPDA-SAP NPs can pass through the upper digestive tract smoothly and finally accumulate in the inflamed colon. Through the synergistic effect of anti-inflammation and antioxidation, it can effectively reduce the expression of pro-inflammatory factors and enhance the intestinal mucosal barrier, and finally significantly alleviate the symptoms of colitis in mice. Furthermore, we confirmed that PAA@MPDA-SAP NPs have good biocompatibility and anti-inflammatory repair ability under inflammation induction through human colonic organoids. In summary, this work provides a theoretical basis for the development of nanomedicines for IBD therapy.

Keywords: Inflammation bowel disease; Mesoporous polydopamine nanomedicine; ROS scavenging; Synergetic therapy; pH-responsive drug release.