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Heart-targeted amelioration of sepsis-induced myocardial dysfunction by microenvironment responsive nitric oxide nanogenerators in situ.
Ouyang, Minzhi; Ouyang, Xiangnan; Peng, Zefang; Liu, Minghui; Xu, Ganqiong; Zou, Zhen; Zhang, Ming; Shang, Quanliang.
  • Ouyang M; Department of Ultrasound Diagnosis, Second Xiangya Hospital, Central South University, Changsha, 410011, China.
  • Ouyang X; Department of Ultrasound Diagnosis, Second Xiangya Hospital, Central South University, Changsha, 410011, China.
  • Peng Z; Department of Ultrasound, Hunan Provincial People's Hospital, The First Affiliated of Hunan Normal University, No. 61 Jiefang Road (W), Changsha, China.
  • Liu M; Department of Ultrasound Diagnosis, Second Xiangya Hospital, Central South University, Changsha, 410011, China.
  • Xu G; Department of Ultrasound Diagnosis, Second Xiangya Hospital, Central South University, Changsha, 410011, China.
  • Zou Z; Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, China.
  • Zhang M; Department of Ultrasound Diagnosis, Second Xiangya Hospital, Central South University, Changsha, 410011, China. zm7626@csu.edu.cn.
  • Shang Q; Department of Ultrasound Diagnosis, Second Xiangya Hospital, Central South University, Changsha, 410011, China. sqljsdh@csu.edu.cn.
J Nanobiotechnology ; 20(1): 263, 2022 Jun 07.
Article in English | MEDLINE | ID: covidwho-1881261
ABSTRACT

BACKGROUND:

A balanced endogenous level of bioavailable nitric oxide (NO) plays a key role in maintaining cardiovascular homeostasis. The bioactive NO level in the cardiomyocytes was much reduced during sepsis. However, it is clinically challenging for the NO gas therapy due to the lack of spatial and temporal release system with precise control. The purpose of this study is to design a NO-releasing biomaterial with heart-targeted capability responsive to the infectious microenvironment, thus ameliorating lipopolysaccharide (LPS)-induced cardiac dysfunction.

RESULTS:

The heart-targeted NO delivery and in situ releasing system, PCM-MSN@LA, was synthesized using hollow mesoporous silica nanoparticles (MSN) as the carrier, and L-arginine (LA) as the NO donor. The myocardial delivery was successfully directed to heart by specific peptide (PCM) combined with low-intensity focused ultrasound (LIFU) guidance. The myocardial system synthesized NO from the LA released from PCM-MSN@LA in the presence of increased endogenous nitric oxide synthase (NOS) activity induced by LPS. This targeted NO release in situ achieved extraordinary protective effects against LPS-challenged myocardial injury by reducing the recruitment of inflammatory cells, inhibiting oxidative stress and maintaining the mitochondria integrity. In particular, this protection was not compromised by simultaneous circulation collapse as an adverse event in the context.

CONCLUSIONS:

PCM-MSN@LA + LIFU exhibited extraordinary cardioprotective effects against severe sepsis in the hearts of LPS-treated animals without the side effect of NO diffusion. This technology has great potential to be served as a novel therapeutic strategy for sepsis-induced myocardial injury.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Sepsis / Nitric Oxide Type of study: Prognostic study Limits: Animals Language: English Journal: J Nanobiotechnology Year: 2022 Document Type: Article Affiliation country: S12951-022-01457-Y

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Sepsis / Nitric Oxide Type of study: Prognostic study Limits: Animals Language: English Journal: J Nanobiotechnology Year: 2022 Document Type: Article Affiliation country: S12951-022-01457-Y