MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou 350116, People's Republic of China.
Fujian Key Laboratory of Functional Marine Sensing Materials, Center for Advanced Marine Materials and Smart Sensors, Minjiang University, Fuzhou 350108, People's Republic of China.
Anal Chem. 2020 Nov 17;92(22):15179-15186. doi: 10.1021/acs.analchem.0c03746. Epub 2020 Oct 28.
Engineering a functional nanoplatform that integrates dynamic monitoring of endogenous biomarkers and a stimuli-activated therapeutic mode is promising for early diagnosis and treatment of cancers. In this study, we developed an intelligent DNA nanohydrogel with specific targeting capability that can be stimuli-activated for both in vitro telomerase detection and in vivo telomerase-triggered gene therapy. The DNA nanohydrogel was formed simply by the self-assembly of two Y-shaped DNA units and a double-stranded DNA linker labeled with fluorophores and loaded with therapeutic siRNA. When intracellular telomerase was overexpressed, the DNA nanohydrogel collapsed owing to the prolongation of the telomeric primer at the terminal sequence of one of the Y-shaped DNA units. As a result, the quenched fluorescence due to fluorescence resonance energy transfer (FRET) of the DNA nanohydrogel recovered and the trapped siRNA was released, enabling the accurate detection and imaging of intracellular telomerase activity as well as effective gene therapy of tumors. Benefiting from the great biocompatibility, specificity, and stimuli-responsive property, the developed DNA nanoplatform provides a new opportunity for precise cancer diagnosis and treatment as well as other biological applications.
工程化的功能纳米平台，集成了内源性生物标志物的动态监测和刺激激活治疗模式，有望实现癌症的早期诊断和治疗。在本研究中，我们开发了一种具有特定靶向能力的智能 DNA 纳米水凝胶，可对体外端粒酶检测和体内端粒酶触发的基因治疗进行刺激激活。DNA 纳米水凝胶通过两个 Y 形 DNA 单元和一条双链 DNA 接头的自组装形成，接头标记有荧光团并负载有治疗性 siRNA。当细胞内端粒酶过度表达时，由于 Y 形 DNA 单元末端序列上的端粒引物延长，DNA 纳米水凝胶坍塌。结果，由于 DNA 纳米水凝胶的荧光共振能量转移（FRET）而猝灭的荧光恢复，并且被捕获的 siRNA被释放，从而能够准确检测和成像细胞内端粒酶活性，并有效进行肿瘤基因治疗。得益于极好的生物相容性、特异性和刺激响应性，所开发的 DNA 纳米平台为精确的癌症诊断和治疗以及其他生物应用提供了新的机会。
