Aguilera-Correa John Jairo, Tasrini Yara, Gisbert-Garzarán Miguel, Boulay Aude, Carvalho Tamara, Blanchet Fabien P, Vallet-Regí María, Kremer Laurent
Centre National de la Recherche Scientifique UMR 9004, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier, Montpellier, France.
CIBERINFEC-CIBER de Enfermedades Infecciosas, Madrid, Spain.
Nat Commun. 2025 Aug 11;16(1):7388. doi: 10.1038/s41467-025-62623-y.
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.
海分枝杆菌是一种常见的与皮肤感染相关的非结核分枝杆菌，其治疗极具挑战性，这凸显了开发新治疗方法的必要性。在此，我们报道了用一系列三苯基膦（TPP）取代基对介孔二氧化硅纳米颗粒（MSN）进行功能化，这赋予了它们在体外以及在受感染的THP - 1细胞内对海分枝杆菌表面的亲和力。这些纳米颗粒在细菌表面的存在会阻止人类巨噬细胞和树突状细胞对它们的摄取。当负载多西环素时，该纳米系统在浮游培养物、生物膜以及海分枝杆菌感染的巨噬细胞中发挥强大的抗菌作用。令人惊讶的是，在海分枝杆菌/斑马鱼感染模型中，负载多西环素的纳米颗粒与细菌载量的显著降低和高胚胎存活率相关。这些结果表明，所提出的MSN纳米系统是治疗海分枝杆菌感染以及可能针对更广泛范围分枝杆菌感染的一种有前景的替代方法。
