Pathologically triggered in situ aggregation of nanoparticles for inflammation-targeting amplification and therapeutic potentiation.
10.1016/j.apsb.2022.07.013
- Author:
Qiang NIE
1
;
Chenwen LI
1
;
Yu WANG
2
;
Yi HU
1
;
Wendan PU
1
;
Qixiong ZHANG
1
;
Jiajun CAI
1
;
Yongyao LIN
1
;
Gang LI
1
;
Chenping WANG
1
;
Lanlan LI
1
;
Yin DOU
1
;
Jianxiang ZHANG
1
Author Information
1. Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing 400038, China.
2. Department of Radiology, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing 400030, China.
- Publication Type:Journal Article
- Keywords:
Inflammatory disease;
Myeloperoxidase;
Nanoparticles;
Nanotherapy;
Reactive oxygen species;
Surface engineering;
Targeted therapy;
Triggerable aggregation
- From:
Acta Pharmaceutica Sinica B
2023;13(1):390-409
- CountryChina
- Language:English
-
Abstract:
Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles via phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactide-co-glycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated in vivo efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.
