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源自藻酸盐的用于基因递送的阳离子碳量子点:一步合成及细胞摄取

Cationic carbon quantum dots derived from alginate for gene delivery: One-step synthesis and cellular uptake.

作者信息

Zhou Jie, Deng Wenwen, Wang Yan, Cao Xia, Chen Jingjing, Wang Qiang, Xu Wenqian, Du Pan, Yu Qingtong, Chen Jiaxin, Spector Myron, Yu Jiangnan, Xu Ximing

机构信息

Department of Pharmaceutics, School of Pharmacy, and Center for Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang 212001, PR China.

Department of Orthopedic Surgery, Harvard Medical School, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.

出版信息

Acta Biomater. 2016 Sep 15;42:209-219. doi: 10.1016/j.actbio.2016.06.021. Epub 2016 Jun 16.

Abstract

UNLABELLED

Carbon quantum dots (CQDs), unlike semiconductor quantum dots, possess fine biocompatibility, excellent upconversion properties, high photostability and low toxicity. Here, we report multifunctional CQDs which were developed using alginate, 3% hydrogen peroxide and double distilled water through a facile, eco-friendly and inexpensive one-step hydrothermal carbonization route. In this reaction, the alginate served as both the carbon source and the cationization agent. The resulting CQDs exhibited strong and stable fluorescence with water-dispersible and positively-charged properties which could serve as an excellent DNA condensation. As non-viral gene vector being used for the first time, the CQDs showed considerably high transfection efficiency (comparable to Lipofectamine2000 and significantly higher than PEI, p<0.05) and negligible toxicity. The photoluminescence properties of CQDs also permitted easy tracking of the cellular-uptake. The findings showed that both caveolae- and clathrin-mediated endocytosis pathways were involved in the internalization process of CQDs/pDNA complexes. Taken together, the alginate-derived photoluminescent CQDs hold great potential in biomedical applications due to their dual role as efficient non-viral gene vectors and bioimaging probes.

STATEMENT OF SIGNIFICANCE

This manuscript describes a facile and simple one-step hydrothermal carbonization route for preparing optically tunable photoluminescent carbon quantum dots (CQDs) from a novel raw material, alginate. These CQDs enjoy low cytotoxicity, positive zeta potential, excellent ability to condense macromolecular DNA, and most importantly, notably high transfection efficiency. The interesting finding is that the negatively-charged alginate can convert into positively charged CQDs without adding any cationic reagents. The significance of this study is that the cationic carbon quantum dots play dual roles as both non-viral gene vectors and bioimaging probes at the same time, which are most desirable in many fields of applications such as gene therapy, drug delivery, and bioimaging.

摘要

未标记

与半导体量子点不同,碳量子点(CQDs)具有良好的生物相容性、出色的上转换特性、高光稳定性和低毒性。在此,我们报告了通过简便、环保且廉价的一步水热碳化路线,使用海藻酸钠、3%过氧化氢和双蒸水制备的多功能碳量子点。在该反应中,海藻酸钠既是碳源又是阳离子化剂。所得的碳量子点表现出强而稳定的荧光,具有水分散性和带正电荷的特性,可作为出色的DNA凝聚剂。作为首次使用的非病毒基因载体,碳量子点显示出相当高的转染效率(与Lipofectamine2000相当,且显著高于PEI,p<0.05)且毒性可忽略不计。碳量子点的光致发光特性也便于对细胞摄取进行追踪。研究结果表明,小窝蛋白介导的内吞途径和网格蛋白介导的内吞途径均参与了碳量子点/质粒DNA复合物的内化过程。综上所述,海藻酸钠衍生的光致发光碳量子点作为高效的非病毒基因载体和生物成像探针具有双重作用,在生物医学应用中具有巨大潜力。

意义声明

本手稿描述了一种简便且简单的一步水热碳化路线,用于从新型原料海藻酸钠制备光学可调谐的光致发光碳量子点(CQDs)。这些碳量子点具有低细胞毒性、正ζ电位、出色的凝聚大分子DNA的能力,最重要的是,具有显著高的转染效率。有趣的发现是,带负电荷的海藻酸钠无需添加任何阳离子试剂即可转化为带正电荷的碳量子点。本研究的意义在于,阳离子碳量子点同时作为非病毒基因载体和生物成像探针发挥双重作用,这在基因治疗、药物递送和生物成像等许多应用领域中是最理想的。

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