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聚(甲基丙烯酸2-(二乙氨基)乙酯)功能化碳纳米点作为三阴性乳腺癌中用于siRNA递送和Survivin基因沉默的诊疗平台

Poly(2-(diethylamino)ethyl methacrylate)-Functionalized Carbon Nanodots as Theranostic Platforms for siRNA Delivery and Survivin Silencing in Triple-Negative Breast Cancer.

作者信息

Varvarà Paola, Cavallaro Gennara, Mauro Nicolò

机构信息

Laboratory of Biocompatible Polymers, Department of "Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche" STEBICEF, University of Palermo, Via Archirafi 32, 90123 Palermo, Italy.

Fondazione Veronesi, Piazza Velasca 5, 20122 Milano, Italy.

出版信息

Biomacromolecules. 2025 Jun 9;26(6):3666-3679. doi: 10.1021/acs.biomac.5c00267. Epub 2025 May 10.

Abstract

This study describes the development of carbon nanodot (CDs)-based theranostic nanocarriers that integrate gene silencing with fluorescence imaging. Nitrogen- and sulfur-doped CDs were functionalized through controlled radical surface polymerization of 2-(diethylamino)ethyl methacrylate (DEAEMA), yielding self-tracking, cationic siRNA carriers CDs-pDEAEMA. The functionalization of CDs enhanced their fluorescence, broadening the emission spectrum toward the biologically transparent window. Fluorescent CDs-pDEAEMA effectively bound siRNA, remaining stable under physiological conditions, while in vitro studies proved their hemocompatibility and cytocompatibility on human dermal fibroblasts. Moreover, the ability to deliver BIRC5 siRNA was demonstrated in MDA-MB-231, successfully transfecting triple-negative breast cancer cells and resulting in an 80% reduction in the anti-apoptotic protein survivin. Furthermore, uptake studies demonstrated that the theranostic CDs are efficiently internalized in tumor cells and are clearly detectable by fluorescence imaging in the red region. These findings highlight the potential of CDs-pDEAEMA as an advanced theranostic tool for real-time tracking of siRNA therapy of breast cancer.

摘要

本研究描述了基于碳纳米点(CDs)的治疗诊断纳米载体的开发,该载体将基因沉默与荧光成像相结合。通过甲基丙烯酸2-(二乙氨基)乙酯(DEAEMA)的可控自由基表面聚合对氮和硫掺杂的CDs进行功能化,得到可自我追踪的阳离子siRNA载体CDs-pDEAEMA。CDs的功能化增强了其荧光,使发射光谱向生物透明窗口拓宽。荧光CDs-pDEAEMA能有效结合siRNA,在生理条件下保持稳定,而体外研究证明了它们对人皮肤成纤维细胞的血液相容性和细胞相容性。此外,在MDA-MB-231细胞中证明了其递送BIRC5 siRNA的能力,成功转染三阴性乳腺癌细胞并使抗凋亡蛋白生存素减少80%。此外,摄取研究表明,治疗诊断用CDs能有效地内化于肿瘤细胞中,并且在红色区域通过荧光成像可清晰检测到。这些发现突出了CDs-pDEAEMA作为一种先进的治疗诊断工具用于实时追踪乳腺癌siRNA治疗的潜力。

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