Sequential delivery of PD-1/PD-L1 blockade peptide and IDO inhibitor for immunosuppressive microenvironment remodeling via an MMP-2 responsive dual-targeting liposome.
10.1016/j.apsb.2023.02.009
- Author:
Chuan HU
1
;
Yujun SONG
1
;
Yiwei ZHANG
1
;
Siqin HE
1
;
Xueying LIU
1
;
Xiaotong YANG
1
;
Tao GONG
1
;
Yuan HUANG
1
;
Huile GAO
1
Author Information
1. Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
- Publication Type:Journal Article
- Keywords:
Breast cancer;
Cascade targeting;
ICBs;
IDO inhibitors;
Immunosuppressive microenvironment;
Immunotherapy;
Liposome;
MMP-2 responsive
- From:
Acta Pharmaceutica Sinica B
2023;13(5):2176-2187
- CountryChina
- Language:English
-
Abstract:
Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.
