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基于膜蛋白表位靶向识别的荧光双印迹纳米粒子的高效药物递送和细胞成像。

Highly Effective Drug Delivery and Cell Imaging Using Fluorescent Double-Imprinted Nanoparticles by Targeting Recognition of the Epitope of Membrane Protein.

机构信息

College of Chemistry, Research Center for Analytical Sciences, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition , Nankai University , Tianjin 300071 , China.

Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071 , China.

出版信息

Anal Chem. 2019 Oct 15;91(20):12696-12703. doi: 10.1021/acs.analchem.9b02123. Epub 2019 Sep 26.

DOI:10.1021/acs.analchem.9b02123
PMID:31532634
Abstract

Nanocarriers with both targeting ability and stable loading of drugs can more effectively deliver drugs to precise tumor sites for therapeutic effects. Accordingly, we have rationally designed fluorescent molecularly imprinted polymer nanoparticles (FMIPs), which use N-terminal epitope of P32 membrane protein as the primary template and doxorubicin (DOX) as the secondary template. The DOX imprinted cavity can stably carry the drug and the epitope-imprinted cavity allows FMIPs to actively recognize the P32-positive 4T1 cancer cells. The targeted therapeutic effect of DOX-loaded FMIPs (FMIPs@DOX) is investigated in vitro and in vivo. The FMIPs@DOX only causes apoptosis in 4T1 cancer cells compared to C8161 cells (expressing low level of P32). In addition, highly effective inhibition of 4T1 malignant breast tumors using FMIPs@DOX is achieved in the model of tumor-bearing mice. Importantly, the antitumor effect achieved by intravenous injection of FMIPs@DOX is almost identical to that by intratumoral injection. Furthermore, the FMIPs can serve as a targeted fluorescence imaging agent due to the high specificity of the epitope-imprinted cavity and the stable fluorescence of the embedded silicon nanoparticles. These results demonstrate the effectiveness of the FMIPs for active targeted drug delivery and imaging. Furthermore, the FMIPs provide a direction for drug-loaded nanocarrier.

摘要

具有靶向能力和药物稳定负载能力的纳米载体可以更有效地将药物递送到精确的肿瘤部位,以实现治疗效果。因此,我们合理设计了荧光分子印迹聚合物纳米粒子(FMIPs),它使用 P32 膜蛋白的 N 端表位作为主要模板,阿霉素(DOX)作为二级模板。DOX 印迹腔可以稳定地携带药物,而表位印迹腔允许 FMIPs 主动识别 P32 阳性 4T1 癌细胞。我们研究了载 DOX 的 FMIPs(FMIPs@DOX)的体外和体内靶向治疗效果。与 C8161 细胞(表达低水平的 P32)相比,FMIPs@DOX 仅导致 4T1 癌细胞凋亡。此外,在荷瘤小鼠模型中,FMIPs@DOX 对 4T1 恶性乳腺肿瘤具有高度有效的抑制作用。重要的是,FMIPs@DOX 通过静脉注射实现的抗肿瘤效果几乎与瘤内注射相同。此外,由于表位印迹腔的高特异性和嵌入硅纳米粒子的稳定荧光,FMIPs 可以作为靶向荧光成像剂。这些结果证明了 FMIPs 用于主动靶向药物递送和成像的有效性。此外,FMIPs 为载药纳米载体提供了一个方向。

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