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
  • 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].
PMID: 36270453 DOI: 10.1016/j.nano.2022.102618
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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