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基于多价适配体DNA纳米组装体的近红外碳点与滚环扩增用于乳腺癌的协同治疗

Polyvalent aptamer DNA nanoassembly based near-infrared carbon dots and rolling circle amplification for synergistic therapy of breast cancer.

作者信息

Ning Gan, Wang Fang, Zhang Ruyan, Du Huan, Weng Tianxin, Wang Xiufeng, Zhou Ting, Zhang Guodong, Zhang Zhiqing

机构信息

College of Chemistry and Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China.

College of Chemistry and Chemical Engineering, China University of Petroleum (East China), Qingdao 266580, China.

出版信息

Int J Biol Macromol. 2025 May;310(Pt 3):143343. doi: 10.1016/j.ijbiomac.2025.143343. Epub 2025 Apr 23.

DOI:10.1016/j.ijbiomac.2025.143343
PMID:40274149
Abstract

Integrating imaging and therapy is of great significance in the field of tumor treatment. Here, we report a polyvalent aptamer nanoplatform for breast cancer cell treatment based on rolling circle amplification (RCA). The platform consists of a long single-stranded DNA scaffold from RCA and short-stranded DNAs with various functions. One short strand is linked to near-infrared carbon dots (NIR-CDs), another carries a MUC1 aptamer targeting cancer cells, and the third loads small interfering RNA (siRNA) for gene therapy. Doxorubicin (Dox) attaches to the platform via CG base pairs, integrating fluorescence targeting, photothermal therapy (PTT), gene therapy, and chemotherapy. Aptamer enhances breast cancer cell uptake of the platform. NIR-CDs serve as fluorescence imaging agents and are used for PTT. When deoxyribonucleases degrade the nanoplatform, Dox is released and then exerts its chemotherapeutic effect. SiRNA can form the RNA-induced silencing complex to reduce drug tolerance and enhance the efficacy of loaded drugs. The experimental results show that the platform can accumulate in cancer cells, exert a killing effect on them, and meanwhile reduce side effects on normal cells. In summary, this study expands the application of DNA materials in biomedicine by constructing a diagnostic and therapeutic platform that integrates NIR-CDs and RCA.

摘要

在肿瘤治疗领域,将成像与治疗相结合具有重要意义。在此,我们报道了一种基于滚环扩增(RCA)的用于乳腺癌细胞治疗的多价适配体纳米平台。该平台由RCA产生的长单链DNA支架和具有各种功能的短链DNA组成。一条短链与近红外碳点(NIR-CDs)相连,另一条携带靶向癌细胞的MUC1适配体,第三条负载用于基因治疗的小干扰RNA(siRNA)。阿霉素(Dox)通过CG碱基对附着在该平台上,整合了荧光靶向、光热疗法(PTT)、基因治疗和化疗。适配体增强了该平台对乳腺癌细胞的摄取。NIR-CDs用作荧光成像剂并用于PTT。当脱氧核糖核酸酶降解纳米平台时,Dox被释放,然后发挥其化疗作用。SiRNA可形成RNA诱导沉默复合体以降低耐药性并增强负载药物的疗效。实验结果表明,该平台可在癌细胞中积累,对其发挥杀伤作用,同时减少对正常细胞的副作用。总之,本研究通过构建整合NIR-CDs和RCA的诊断和治疗平台,拓展了DNA材料在生物医学中的应用。

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