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用于具有高信噪比的原位肝细胞癌靶向光声成像的超小杂化蛋白-硫化铜纳米颗粒。

Ultrasmall hybrid protein-copper sulfide nanoparticles for targeted photoacoustic imaging of orthotopic hepatocellular carcinoma with a high signal-to-noise ratio.

机构信息

Department of Ultrasound, The Second Clinical College of Jinan University, Shenzhen People's Hospital, 518020 Shenzhen, China.

出版信息

Biomater Sci. 2018 Dec 18;7(1):92-103. doi: 10.1039/c8bm00767e.

DOI:10.1039/c8bm00767e
PMID:30358774
Abstract

Although photoacoustic imaging combined with second near infrared (NIR II) molecular probes for tumor diagnosis has drawn tremendous attention during the past few decades, the targeted photoacoustic imaging of orthotopic hepatocellular carcinoma (HCC) still remains a challenge due to high liver vascularization and non-specificity of probes in liver tumors. Herein, we report on cyclic arginine-glycine-aspartic acid (cRGD) peptide conjugated ultrasmall CuS nanoparticles (CuS@BSA-RGD NPs) which encapsulate bovine serum albumin (BSA) and possess high optical absorption at 1064 nm. The encapsulation of BSA results in great biocompatibility of CuS@BSA-RGD NPs along with excellent photostability and physiological stability. The cRGD conjugation enables the improvement of tumor uptake of CuS@BSA-RGD NPs by virtue of its positive tumor cell targeting capability. The efficient accumulation of CuS@BSA-RGD NPs in the tumor over time after intravenous administration to orthotopic HCC bearing mice was achieved, which resulted in highly sensitive photoacoustic visualization of the tumor region. Toxicity studies indicate that CuS@BSA-RGD NPs exhibited negligible systemic toxicity in vivo. The results demonstrate that the CuS@BSA-RGD NPs might hold great promise for future imaging and diagnosis of cancer.

摘要

尽管光声成像结合第二代近红外(NIR II)分子探针在过去几十年中引起了极大的关注,但由于肝脏血管化程度高和肝脏肿瘤中探针的非特异性,原位肝癌(HCC)的靶向光声成像仍然是一个挑战。在此,我们报告了一种循环精氨酸-甘氨酸-天冬氨酸(cRGD)肽偶联的超小 CuS 纳米粒子(CuS@BSA-RGD NPs),其包裹牛血清白蛋白(BSA),并在 1064nm 处具有高吸光度。BSA 的包裹导致 CuS@BSA-RGD NPs 具有出色的生物相容性、优异的光稳定性和生理稳定性。由于其对肿瘤细胞的靶向能力,cRGD 偶联提高了 CuS@BSA-RGD NPs 的肿瘤摄取。将 CuS@BSA-RGD NPs 静脉注射到荷有原位 HCC 的小鼠后,随着时间的推移,其在肿瘤中的有效积累实现了对肿瘤区域的高灵敏度光声可视化。毒性研究表明,CuS@BSA-RGD NPs 在体内表现出可忽略的系统毒性。这些结果表明,CuS@BSA-RGD NPs 可能为癌症的未来成像和诊断带来巨大的希望。

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