Gao Feng, Guo Lichao, Lin Wanjuan, Zhang Xiaobo, Zhan Qichen, Cao Peng, Ju Huangxian, Zhang Yue
State Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing 210023, China.
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
Anal Chem. 2025 May 27;97(20):10699-10708. doi: 10.1021/acs.analchem.5c00581. Epub 2025 May 13.
The delayed detection and recurrence of cancer lead to disappointing cure rates, underscoring the imperative for exploring precise early tumor diagnosis techniques. Despite the superior biocompatibility and flexible programmability of DNA nanoprobes for tumor imaging, intricate designs with multiple oligonucleotide sequences are always indispensable, which significantly hinder their clinical application and commercial development. To construct a simply designed DNA nanoprobe, here, we constructed a universal stimuli-responsive nanohydrogel through the hybridization of the staple strand and skeleton strand. Through a simple substitution of the staple strand, this hydrogel can be adapted for the response to different targets without necessitating a series of subsequent revisions and synthesis optimization. To achieve near-infrared II region (NIR-II) fluorescence imaging, alkynyl-modified NIR-II fluorescent dyes are labeled at two ends of bent staple strands and display weak fluorescence because of the aggregation-caused quenching effect. The highly expressed ATP or cytokine in tumor cells activates the liberation of staples and collapse of the bent configuration, which generates fluorescence recovery for tumor imaging. Moreover, this nanohydrogel also allows for the targeted release of anticancer drugs intercalated in the DNA helix. By integration of NIR-II fluorescent dyes, this versatile nanohydrogel enables precise diagnosis and treatment of early tumors. The straightforward design demonstrates low cost and easy adaptability for multitarget detection, highlighting its significant implications for the advancement of DNA nanotechnology in clinical application and commercialization production.
癌症的延迟检测和复发导致治愈率不尽人意，这凸显了探索精确的早期肿瘤诊断技术的紧迫性。尽管DNA纳米探针在肿瘤成像方面具有卓越的生物相容性和灵活的可编程性，但具有多个寡核苷酸序列的复杂设计始终不可或缺，这严重阻碍了它们的临床应用和商业开发。为了构建一种设计简单的DNA纳米探针，我们在此通过短链和骨架链的杂交构建了一种通用的刺激响应性纳米水凝胶。通过简单替换短链，这种水凝胶无需一系列后续修改和合成优化就能适应对不同靶标的响应。为了实现近红外II区（NIR-II）荧光成像，炔基修饰的NIR-II荧光染料标记在弯曲短链的两端，由于聚集诱导猝灭效应而显示出微弱的荧光。肿瘤细胞中高表达的ATP或细胞因子激活短链的释放并导致弯曲构象的坍塌，从而产生用于肿瘤成像的荧光恢复。此外，这种纳米水凝胶还允许插入DNA螺旋中的抗癌药物靶向释放。通过整合NIR-II荧光染料，这种多功能纳米水凝胶能够实现早期肿瘤的精确诊断和治疗。这种简单的设计展示了低成本和对多靶点检测的易适应性，突出了其对DNA纳米技术在临床应用和商业化生产中的发展的重大意义。
