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

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

  • Nanomedicine. 2022 Oct 18;102618. doi: 10.1016/j.nano.2022.102618.
Jing-Jing Ji 1 Shang-Yu Chen 2 Zi-Wei Yang 3 Rui Zhang 3 Ling-Lin Qian 3 Yu Jiang 3 Jia-Qi Guo 3 Ya Wu 3 Qu-Li Fan 2 Yu-Yu Yao 4 Peng-Fei Sun 5
Affiliations

Affiliations

  • 1 Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210009, China; Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310009, China.
  • 2 State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China.
  • 3 Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210009, China.
  • 4 Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210009, China. Electronic address: [email protected].
  • 5 State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, Nanjing 210023, China. Electronic address: [email protected].
Abstract

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.

Keywords

Ferroptosis; Gel/BTN; I/R; Mir-196c-3p; NIR-II.

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