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内源性 mRNA 触发 DNA-Au 纳米机器用于原位成像和靶向多模式协同癌症治疗。

Endogenous mRNA Triggered DNA-Au Nanomachine for In Situ Imaging and Targeted Multimodal Synergistic Cancer Therapy.

机构信息

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.

School of Mechanical and Materials Engineering, Washington State University, Pullman, WA, 99164, USA.

出版信息

Angew Chem Int Ed Engl. 2021 Mar 8;60(11):5948-5958. doi: 10.1002/anie.202012801. Epub 2021 Jan 28.

Abstract

The development of versatile nanotheranostic platforms that integrate both diagnostic and therapeutic functions have always been an intractable challenge in precise cancer treatment. Herein, an aptamer-tethered deoxyribonucleic acids-gold particle (Apt-DNA-Au) nanomachine has been developed for in situ imaging and targeted multimodal synergistic therapy of mammary carcinoma. Upon specifically internalized into MCF-7 cells, the tumor-related TK1 mRNA activates the Apt-DNA-Au nanomachine by DNA strand displacement cascades, resulting in the release of the fluorophore and antisense DNA as well as the aggregation of AuNPs for in situ imaging, suppression of survivin expression and photothermal therapy, respectively. Meanwhile, the controlled released drugs are used for chemotherapy, while under the laser irradiation the loaded photosensitizer produces reactive oxygen species (ROS) for photodynamic therapy. The results confirm that the proposed Apt-DNA-Au nanomachine provides a powerful nanotheranostic platform for in situ imaging-guided combinatorial anticancer therapy.

摘要

多功能纳米诊疗平台的发展,集诊断和治疗功能于一体,一直是精确癌症治疗中的一个难题。在此,我们开发了一种适体连接的脱氧核糖核酸-金颗粒(Apt-DNA-Au)纳米机,用于原位成像和靶向多模式协同治疗乳腺癌。Apt-DNA-Au 纳米机特异性地被 MCF-7 细胞内化后,肿瘤相关的 TK1mRNA 通过 DNA 链置换级联反应激活 Apt-DNA-Au 纳米机,导致荧光团和反义 DNA 的释放以及 AuNPs 的聚集,分别用于原位成像、抑制生存素表达和光热治疗。同时,控释药物用于化疗,而在激光照射下,负载的光敏剂产生活性氧(ROS)用于光动力治疗。结果证实,所提出的 Apt-DNA-Au 纳米机为原位成像引导的组合抗癌治疗提供了一个强大的纳米诊疗平台。

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