Nature-Inspired Smart DNA Nanodoctor for Activatable In Vivo Cancer Imaging and In Situ Drug Release Based on Recognition-Triggered Assembly of Split Aptamer
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- 作者：Yanli Lei ; Jinlu Tang ; Hui Shi ; Xiaosheng Ye ; Xiaoxiao He ; Fengzhou Xu ; Lv’an Yan ; Zhenzhen Qiao ; Kemin Wang
- 刊名：Analytical Chemistry
- 出版年：2016
- 出版时间：December 6, 2016
- 年：2016
- 卷：88
- 期：23
- 页码：11699-11706
- 全文大小：522K
- ISSN：1520-6882
文摘
DNA-based activatable theranostic nanoprobes are still unmet for in vivo applications. Here, by utilizing the “induced-fit effect”, a smart split aptamer-based activatable theranostic probe (SATP) was first designed as “nanodoctor” for cancer-activated in vivo imaging and in situ drug release. The SATP assembled with quenched fluorescence and stable drug loading in its free state. Once binding to target proteins on cell surface, the SATP disassembled due to recognition-triggered reassembly of split aptamers with activated signals and freed drugs. As proof of concept, split Sgc8c against CEM cancer was used for theranostic studies. Benefiting from the design without blocking aptamer sequence, the SATP maintained an excellent recognition ability similar to intact Sgc8c. An “incubate-and-detect” assay showed that the SATP could significantly lower background and improve signal-to-background ratio (∼4.8 times of “always on” probes), thus affording high sensitivity for CEM cell analysis with 46 cells detected. Also, its high selectivity to target cells was demonstrated in analyzing mixed cell samples and serum samples. Then, using doxorubicin as a model, highly specific drug delivery and cell killing was realized with minimized toxicity to nontarget cells. Moreover, in vivo and ex vivo investigations also revealed that the SATP was specifically activated by CEM tumors inside mice. Especially, contrast-enhanced imaging was achieved in as short as 5 min, thus, laying a foundation for rapid diagnosis and timely therapy. As a biocompatible and target-activatable strategy, the SATP may be widely applied in cancer theranostics.