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<p>Treatments of <i>Mycobacterium marinum</i>, a common non-tuberculous mycobacterium associated with cutaneous infections are very challenging, emphasizing the development of new therapeutic approaches. Here we report the functionalization of mesoporous silica nanoparticles (MSN) with a series of triphenylphosphonium (TPP) substituents, which endowed them with affinity towards the surface of <i>M. marinum</i> in vitro, as well as within infected THP-1 cells. The presence of these nanoparticles at the bacterial surface prevents their uptake by human macrophages and dendritic cells. When loaded with doxycycline, the nanosystem exerts a potent anti-bacterial effect in planktonic cultures, biofilms, and in <i>M. marinum</i>-infected macrophages. Strikingly, in the <i>M. marinum/</i>zebrafish infection model, the doxycycline-loaded nanoparticles are associated with a pronounced decrease in the bacterial burden and a high embryo survival rate. These results disclose the proposed MSN nanosystems as a promising alternative for the treatment of <i>M. marinum</i> infection and, presumably, against a broader range of mycobacterial infections.</p>

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In vivo antimicrobial activity of engineered mesoporous silica nanoparticles targeting intracellular mycobacteria

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月11日

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  • John Jairo Aguilera-Correa,
  • Yara Tasrini,
  • Miguel Gisbert-Garzarán,
  • Aude Boulay,
  • Tamara Carvalho,
  • Fabien P. Blanchet,
  • María Vallet-Regí,
  • Laurent Kremer

摘要

Treatments of Mycobacterium marinum, a common non-tuberculous mycobacterium associated with cutaneous infections are very challenging, emphasizing the development of new therapeutic approaches. Here we report the functionalization of mesoporous silica nanoparticles (MSN) with a series of triphenylphosphonium (TPP) substituents, which endowed them with affinity towards the surface of M. marinum in vitro, as well as within infected THP-1 cells. The presence of these nanoparticles at the bacterial surface prevents their uptake by human macrophages and dendritic cells. When loaded with doxycycline, the nanosystem exerts a potent anti-bacterial effect in planktonic cultures, biofilms, and in M. marinum-infected macrophages. Strikingly, in the M. marinum/zebrafish infection model, the doxycycline-loaded nanoparticles are associated with a pronounced decrease in the bacterial burden and a high embryo survival rate. These results disclose the proposed MSN nanosystems as a promising alternative for the treatment of M. marinum infection and, presumably, against a broader range of mycobacterial infections.