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用于靶向癌症治疗的氧化还原响应性二肽纳米结构

Redox-Responsive Dipeptide Nanostructures toward Targeted Cancer Therapy.

作者信息

Chibh Sonika, Kour Avneet, Yadav Nitin, Kumar Pankaj, Yadav Pratik, Chauhan Virander Singh, Panda Jiban Jyoti

机构信息

Institute of Nano Science and Technology, Phase-10, Sector 64, Mohali, Punjab 160062, India.

International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India.

出版信息

ACS Omega. 2020 Feb 11;5(7):3365-3375. doi: 10.1021/acsomega.9b03547. eCollection 2020 Feb 25.

DOI:10.1021/acsomega.9b03547
PMID:32118151
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7045500/
Abstract

Materials that exhibit responsiveness toward biological signals are currently subjected to intense research in the field of drug delivery. In our study, we tried to develop cancer-targeted and redox-responsive nanoparticles (NPs) from disulfide-linked oxidized cysteine-phenylalanine (CFO). The NPs were conjugated with folic acid (FA) to specifically target cancer cells, and the presence of disulfide bonds would enabled the disintegration of the particles in the presence of elevated levels of glutathione (GSH) in cancer cells. Anticancer drug doxorubicin (Dox) was successfully loaded inside the disulfide-linked nanoparticles (CFO-Dox-NPs), which further demonstrated stimuli-responsive drug release in the presence of GSH. We have also demonstrated enhanced uptake of FA-derivatized NPs (FA-CFO-NPs) in cancerous cells (C6 glioma and B16F10 melanoma cells) than in normal cells (HEK293T cells) due to the overexpression of FA receptors on the surface of cancer cells. Cytotoxicity studies in C6 cells and B16F10 cells further revealed enhanced efficacy of Dox loaded (FA-CFO-Dox-NPs) as compared to the native drug. The findings of this study clearly demonstrated that the disulfide-linked nanoparticle system may provide a promising selective drug delivery platform in cancer cells.

摘要

对生物信号具有响应性的材料目前在药物递送领域受到广泛研究。在我们的研究中，我们尝试用二硫键连接的氧化半胱氨酸 - 苯丙氨酸（CFO）开发具有癌症靶向性和氧化还原响应性的纳米颗粒（NPs）。这些纳米颗粒与叶酸（FA）偶联以特异性靶向癌细胞，并且二硫键的存在会使颗粒在癌细胞中谷胱甘肽（GSH）水平升高时解体。抗癌药物阿霉素（Dox）成功负载在二硫键连接的纳米颗粒（CFO - Dox - NPs）内，这进一步证明了在GSH存在下的刺激响应性药物释放。我们还证明，由于癌细胞表面FA受体的过表达，与正常细胞（HEK293T细胞）相比，FA衍生化的纳米颗粒（FA - CFO - NPs）在癌细胞（C6胶质瘤细胞和B16F10黑色素瘤细胞）中的摄取增强。在C6细胞和B16F10细胞中的细胞毒性研究进一步表明，与天然药物相比，负载Dox的纳米颗粒（FA - CFO - Dox - NPs）具有更高的疗效。这项研究的结果清楚地表明，二硫键连接的纳米颗粒系统可能为癌细胞提供一个有前景的选择性药物递送平台。

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