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Enhancing intracellular mRNA precise imaging-guided photothermal therapy with a nucleic acid-based polydopamine nanoprobe

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Abstract

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.

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Funding

This work was supported by the National Natural Science Foundations of China (22064002, 22364021), the Natural Science Foundation of Guangxi Province (2020GXNSFAA159072), the PhD Research Startup Program of Yulin Normal University (G2023Zk04), and the Guangxi University Students Innovative Project (S202310606116).

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  1. Jiayao Xu and Xiaohong Zhong contributed equally to this work.

Authors and Affiliations

  1. 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

    Jiayao Xu, Mingzhu Fan, Yang Xu, Shulong Wang & Zhihui Luo

  2. 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

    Xiaohong Zhong, Yiqi Xu & Yong Huang

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  1. Jiayao Xu
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Xu, J., Zhong, X., Fan, M. et al. Enhancing intracellular mRNA precise imaging-guided photothermal therapy with a nucleic acid-based polydopamine nanoprobe. Anal Bioanal Chem 416, 849–859 (2024). https://doi.org/10.1007/s00216-023-05062-2

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