Delivery of Mir-196c-3p with NIR-II light-triggered gel attenuates cardiomyocyte ferroptosis in cardiac ischemia-reperfusion injury

• Published in: Nanomedicine Vol. 47; p. 102618
• Main Authors: Ji, Jing-jing, Chen, Shang-yu, Yang, Zi-wei, Zhang, Rui, Qian, Ling-lin, Jiang, Yu, Guo, Jia-qi, Wu, Ya, Fan, Qu-li, Yao, Yu-yu, Sun, Peng-fei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-01-2023
• Subjects: Animals; Ferroptosis; Gel/BTN; I/R; Mir-196c-3p; NIR-II; Rats; Reperfusion Injury; Ferroptosis; NIR-II; Mir-196c-3p; I/R; Gel/BTN
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2022.102618

Ferroptosis plays an important role in ischemia-reperfusion (I/R)-induced cardiac injury and there are many defects in current targeted delivery of miRNAs for the treatment of ferroptosis. We herein report a unique hydrogel (Gel) that can be triggered by a near-infrared-II (NIR-II) light with deep tissue penetration and biocompatible maximum permissible exposure (MPE) value for in situ treatment after I/R. The mir-196c-3p mimic (mimics) and photothermal nanoparticles (BTN) were co-encapsulated in an injectable Gel (mimics + Gel/BTN) with NIR-II light-triggered release. Using 1064 nm light irradiation, local microenvironment photothermal-triggered on-demand noninvasive controllable delivery of miRNA was achieved, aiming to inhibit I/R-induced ferroptosis. Consequently, declined ferroptosis in cardiomyocytes and improved cardiac function, survival rate in rats was achieved through the controlled release of Gel/BTN mimics in I/R model to simultaneously inhibit ferroptosis hub genes NOX4, P53, and LOX expression.
Ischemic heart disease is the leading cause of death worldwide. A novel dynamic covalent hydrogel of fructose-containing polymer (PFA) and BOB-containing polymer (PNBA) was successfully constructed, capable of light-triggered release of miRNAs via NIR-II. This work demonstrated that a strategy to noninvasively control release of miRNAs in vivo while providing an effective target for ferroptosis therapy might be a promising treatment for I/R. [Display omitted]
•The hydrogel with NIR-II light-triggered release of the mimics is rationally designed as a promising drug delivery system.•The hydrogel can simultaneously regulate the expression of ferroptosis-related genes LOX, NOX4, and P53.•We successfully performed NIR-II-triggered in vivo fluorescence imaging through the chest cavity as deep as 7 mm.