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A non-residue surface modification strategy for active-targeting fluorescent silica nanoparticles to cellular organelles

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Abstract

Silica nanoparticles (SiNPs) with a chemically modified surface typically have a complicated chemical composition, which can significantly differ from their intended design. In this study, we systematically studied the effects of two surface modification methods on active-targeting of intracellular organelles of SiNPs: (1) the widely used step-by-step approach, which involves modifying SiNPs in two steps, i.e., the outer surface of SiNPs was firstly modified with amino groups and then these amino groups were linked with targeting groups, and (2) a newly developed one-step approach in which the ligand–silane complex is initially synthesized, followed by chemically immobilizing the complex on the surface of SiNPs. In the one-step approach, the molar ratio of reactants was precisely tuned so that there are no reactive groups left on the outer surface of SiNPs. Two essential organelles, mitochondria and the nucleus, were selected to compare the targeting performances of SiNPs synthesized via these two approaches. By characterizing physicochemical properties, including structural properties, the number of amino groups, surface charge, polydispersity, and cell colocalization, we demonstrated that SiNPs synthesized via the one-step approach with no residual linkage groups on their surface showed significantly improved mitochondria- and nucleus-targeting performances. This precise control of surface properties allows for optimized biological behavior and active-targeting efficiency of SiNPs. We anticipate that such simple and efficient synthetic strategies will enable the synthesis of effective SiNPs for active-targeting organelles in various biological applications.

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Data availability

The data that supports the findings of this study are available in the supplementary information of this article. Data available on request.

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Funding

The study was financially supported by the National Natural Science Foundation of China (No. 22274031), National Key R&D Program of China (2022YFC3400700), and Shanghai Municipal Science and Technology Major Project (Grant No. 2017SHZDZX01).

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Authors and Affiliations

  1. Department of Chemistry and Human Phenome Institute, Fudan University, 200433, Shanghai, People’s Republic of China

    Zeyu Zhang, Xiaoai Zhang & Xu-dong Wang

  2. College of Chemistry, Chemical Engineering and Environment, Fujian Province Key Laboratory of Modern Analytical Science and Separation Technology, Minnan Normal University, Zhangzhou, 363000, China

    Qiaowen Zheng, Junying Zhang & Maosheng Zhang

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  1. Zeyu Zhang
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Correspondence to Maosheng Zhang or Xu-dong Wang.

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Zhang, Z., Zhang, X., Zheng, Q. et al. A non-residue surface modification strategy for active-targeting fluorescent silica nanoparticles to cellular organelles. Microchim Acta 191, 181 (2024). https://doi.org/10.1007/s00604-024-06239-x

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