Facile Construction of Near Infrared Fluorescence Nanoprobe with Amphiphilic Protein-Polymer Bioconjugate for Targeted Cell Imaging

Facile Construction of Near Infrared Fluorescence Nanoprobe with Amphiphilic Protein-Polymer Bioconjugate for Targeted Cell Imaging
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使用两亲性蛋白质-聚合物生物缀合物轻松构建用于靶向细胞成像的近红外荧光纳米探针

DOI:
10.1021/acsami.5b05406
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发表时间:
2015-09-02
影响因子:
9.5
通讯作者:
Chang, Jin
Chang, Jin
中科院分区:
材料科学2区
文献类型:
--
作者:
Liu, Zhongyun;Chen, Na;Chang, Jin

文献摘要

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通过在CuInS 2/ZnS量子点(CIS/ZnS QDs)表面包覆一种新型的两亲性生物共轭物,开发了一种简单、直接、可重复的近红外(NIR)荧光纳米探针的构建方法。以牛血清白蛋白(BSA)为亲水链段,聚己内酯(PCL)为疏水链段,通过马来酰亚胺巯基化反应将疏水高分子链与BSA化学偶联,制备了两亲性生物偶联物。通过将CIS/ZnS量子点引入BSA-PCL偶联物的疏水核中,构建的近红外荧光纳米探针在较宽的pH范围(pH 3-10)内表现出优异的荧光性能,并在含有或不含10%胎牛血清的PBS缓冲液(pH = 7.4)中表现出良好的胶体稳定性。BSA外壳的存在有效地减少了非特异性细胞结合,并赋予探针高生物相容性和低毒性。此外,NIR荧光纳米探针可以通过缀合环状Arg-Gly-Asp(cRGD)肽来官能化,并且显示修饰的纳米探针对于靶向整合素α(v)β(3)-过表达的肿瘤细胞成像具有高度选择性。进一步研究了所构建的近红外荧光探针在体内应用的可行性,结果表明其在体内成像方面具有巨大的潜力。这种开发的CIS/ZnS量子点的相转移协议是通用的,适用于其他纳米粒子稳定的疏水配体。
A simple, straightforward, and reproducible strategy for the construction of a near-infrared (NIR) fluorescence nanoprobe was developed by coating CuInS2/ZnS quantum dots (CIS/ZnS QDs) with a novel amphiphilic bioconjugate. The amphiphilic bioconjugate with a tailor-designed structure of bovine serum albumin (BSA) as the hydrophilic segment and poly(e-caprolactone) (PCL) as the hydrophobic part was fabricated by chemical coupling the hydrophobic polymer chain to BSA via the maleimide sulfhydryl reaction. By incorporating CIS/ZnS QDs into the hydrophobic cores of the self-assembly of BSA-PCL conjugate, the constructed NIR fluorescence nanoprobe exhibited excellent fluorescent properties over a wide pH range (pH 3-10) and a good colloidal stability in PBS buffer (pH = 7.4) with or without 10% fetal bovine serum. The presence of the outer BSA shell effectively reduced the nonspecific cellular binding and imparted high biocompatibility and low-toxicity to the probe. Moreover, the NIR fluorescence nanoprobe could be functionalized by conjugating cyclic Arg-Gly-Asp (cRGD) peptide, and the decorated nanoprobe was shown to be highly selective for targeted integrin alpha(v)beta(3)-overexpressed tumor cell imaging. The feasibility of the constructed NIR fluorescence probe in vivo application was further investigated and the results demonstrated its great potential for in vivo imaging. This developed protocol for phase transfer of the CIS/ZnS QDs was universal and applicable to other nanoparticles stabilized with hydrophobic ligands.