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用于肝细胞癌体外磁热疗和体内肝纤维化双重成像的近红外发射多模态纳米系统。

Near infrared-emitting multimodal nanosystem for in vitro magnetic hyperthermia of hepatocellular carcinoma and dual imaging of in vivo liver fibrosis.

机构信息

Department of Chemistry, Indian Institute of Space Sciences and Technology, Thiruvananthapuram, 695547, Kerala, India.

Division of Biophotonics and Imaging, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, Poojappura, Thiruvananthapuram, 695 012, Kerala, India.

出版信息

Sci Rep. 2023 Aug 9;13(1):12947. doi: 10.1038/s41598-023-40143-3.

Abstract

Prolonged usage of traditional nanomaterials in the biological field has posed several short- and long-term toxicity issues. Over the past few years, smart nanomaterials (SNs) with controlled physical, chemical, and biological features have been synthesized in an effort to allay these challenges. The current study seeks to develop theranostic SNs based on iron oxide to enable simultaneous magnetic hyperthermia and magnetic resonance imaging (MRI), for chronic liver damage like liver fibrosis which is a major risk factor for hepatocellular carcinoma. To accomplish this, superparamagnetic iron oxide nanoparticles (SPIONs) were prepared, coated with a biocompatible and naturally occurring polysaccharide, alginate. The resultant material, ASPIONs were evaluated in terms of physicochemical, magnetic and biological properties. A hydrodynamic diameter of 40 nm and a transverse proton relaxation rate of 117.84 mM s pronounces the use of ASPIONs as an efficient MRI contrast agent. In the presence of alternating current of 300 A, ASPIONs could elevate the temperature to 45 °C or more, with the possibility of hyperthermia based therapeutic approach. Magnetic therapeutic and imaging potential of ASPIONs were further evaluated respectively in vitro and in vivo in HepG2 carcinoma cells and animal models of liver fibrosis, respectively. Finally, to introduce dual imaging capability along with magnetic properties, ASPIONs were conjugated with near infrared (NIR) dye Atto 700 and evaluated its optical imaging efficiency in animal model of liver fibrosis. Histological analysis further confirmed the liver targeting efficacy of the developed SNs for Magnetic theranostics and optical imaging as well as proved its short-term safety, in vivo.

摘要

传统纳米材料在生物领域的长期使用引发了一些短期和长期的毒性问题。近年来,为了应对这些挑战,人们合成了具有可控物理、化学和生物学特性的智能纳米材料 (SNs)。本研究旨在基于氧化铁开发治疗诊断一体化的 SNs,以实现磁热疗和磁共振成像 (MRI) 的同步,用于治疗慢性肝损伤,如肝纤维化,这是肝细胞癌的一个主要危险因素。为此,我们制备了超顺磁性氧化铁纳米颗粒 (SPIONs),并将其包覆在具有生物相容性和天然存在的多糖——藻酸盐上。所得的材料,ASPIONs,在物理化学、磁性和生物学性质方面进行了评估。其水动力学直径为 40nm,横向质子弛豫率为 117.84mM·s-1,表明 ASPIONs 可用作高效的 MRI 对比剂。在 300A 交流电流的存在下,ASPIONs 可以将温度升高到 45°C 或更高,从而有可能实现基于热疗的治疗方法。分别在 HepG2 癌细胞和肝纤维化动物模型中对 ASPIONs 的磁性治疗和成像潜力进行了体外和体内评估。最后,为了引入双成像能力和磁性,我们将 ASPIONs 与近红外 (NIR) 染料 Atto 700 缀合,并在肝纤维化动物模型中评估其光学成像效率。组织学分析进一步证实了所开发的 SNs 用于磁治疗和光学成像的肝脏靶向能力,并证明了其在体内的短期安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aca2/10412632/f0ff7349b058/41598_2023_40143_Fig1_HTML.jpg

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