Guangxi Key Lab of Agricultural Resources Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, Yulin, 537000, People's Republic of China.
Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, People's Republic of China.
Anal Bioanal Chem. 2024 Feb;416(4):849-859. doi: 10.1007/s00216-023-05062-2. Epub 2023 Nov 25.
Despite significant advancements in cancer research, real-time monitoring and effective treatment of cancer through non-invasive techniques remain a challenge. Herein, a novel polydopamine (PDA) nucleic acid nanoprobe has been developed for imaging signal amplification of intracellular mRNA and precise photothermal therapy guidance in cancer cells. The PDA nucleic acid nanoprobe (PDA@DNA) is constructed by assembling an aptamer hairpin (H1) labeled with the Cy5 fluorophore and another nucleic acid recognition hairpin (H2) onto PDA nanoparticles (PDA NPs), which have exceptionally high fluorescence quenching ability and excellent photothermal conversion properties. The nanoprobe could facilitate cellular uptake of DNA molecules and their protection from nuclease degradation. Upon recognition and binding to the intracellular mRNA target, a catalytic hairpin assembly (CHA) reaction occurs. The stem of H1 unfolds upon binding, allowing the exposed H1 to hybridize with H2, forming a flat and sturdy DNA double-stranded structure that detaches from the surface of PDA NPs. At the same time, the target mRNA is displaced and engages in a new cyclic reaction, resulting in the recovery and significant amplification of Cy5 fluorescence. Using thymidine kinase1 (TK1) mRNA as a model mRNA, this nanoprobe enables the analysis of TK1 mRNA with a detection limit of 9.34 pM, which is at least two orders of magnitude lower than that of a non-amplifying imaging nucleic acid probe. Moreover, with its outstanding performance for in vitro detection, this nanoprobe excels in precisely imaging tumor cells. Through live-cell TK1 mRNA imaging, it can accurately distinguish between tumor cells and normal cells. Furthermore, when exposed to 808-nm laser irradiation, the nanoprobe fully harnesses exceptional photothermal conversion properties of PDA NPs. This results in a localized temperature increase within tumor cells, which ultimately triggers apoptosis in these tumor cells. The integration of PDA@DNA presents innovative prospects for tumor diagnosis and image-guided tumor therapy, offering the potential for high-precision diagnosis and treatment of tumors.
尽管癌症研究取得了重大进展，但通过非侵入性技术实时监测和有效治疗癌症仍然是一个挑战。在这里，开发了一种新型的聚多巴胺（PDA）核酸纳米探针，用于细胞内 mRNA 的成像信号放大和癌细胞的精确光热治疗指导。PDA 核酸纳米探针（PDA@DNA）是通过将标记有 Cy5 荧光团的适体发夹（H1）和另一个核酸识别发夹（H2）组装到具有异常高荧光猝灭能力和优异光热转换性能的 PDA 纳米颗粒（PDA NPs）上构建的。纳米探针可以促进 DNA 分子的细胞摄取并保护其免受核酸酶降解。在识别并与细胞内的 mRNA 靶标结合后，发生催化发夹组装（CHA）反应。H1 的茎在结合时展开，使暴露的 H1 与 H2 杂交，形成从 PDA NPs 表面脱离的平坦而坚固的 DNA 双链结构。同时，靶 mRNA 被置换并参与新的循环反应，导致 Cy5 荧光的恢复和显著放大。使用胸苷激酶 1（TK1）mRNA 作为模型 mRNA，该纳米探针能够以 9.34 pM 的检测限分析 TK1 mRNA，这至少比非放大成像核酸探针低两个数量级。此外，由于其在体外检测方面的出色性能，该纳米探针能够精确地对肿瘤细胞进行成像。通过活细胞 TK1 mRNA 成像，可以准确区分肿瘤细胞和正常细胞。此外，当暴露于 808nm 激光照射时，纳米探针充分利用 PDA NPs 的卓越光热转换性能。这导致肿瘤细胞内局部温度升高，最终导致这些肿瘤细胞凋亡。PDA@DNA 的集成为肿瘤诊断和图像引导肿瘤治疗提供了创新性的前景，为肿瘤的高精度诊断和治疗提供了潜力。
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