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Host-directed strategies using lipid nanoparticles to reduce mycobacteria survival

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Abstract

Antibiotic-resistant infections and the stagnations in the development of new drugs have increased the demand for new therapeutic approaches against Mycobacterium tuberculosis. Innovative systems that are able to target and eradicate the bacteria in the infected host cells may represent a therapeutic breakthrough while avoiding latency. The development of nanosystems aiming a controlled and targeted intracellular drug release, have proved to increase cytosolic therapeutic concentration while reducing undesired side effects. This work’s main goal was to develop a host-directed strategy against mycobacterial infection through the design of a biocompatible nanocarrier for phage-derived protein delivery, using M. smegmatis as model. Since mycobacterial pathogenicity is strongly supported by the presence of lipids in the cell wall, their degradation induces bacterial destruction through cell wall hydrolysis. Phage-based lipolytic enzymes such as, LysB a mycolylarabinogalactan esterase, represent an appealing therapeutic approach. The herein proposed Ms6 LysB-containing lipid nanocarrier (SLN_LysB) explores the known advantages of nanomedicine-based systems for phagocytic cells selectively targeting thus allowing LysB intracellular accumulation and a more pronounced mycobacterial infection eradication. Adsorption efficiency value indicates the potential of this system as a protein nanocarrier. Moreover, promising outcomes were obtained in host-infected macrophages treated with SLN_LysB. The results show that the herein proposed strategy was more effective in inhibiting the growth of M. smegmatis than free LysB, which might be related to the nanocarrier internalization. Acting as effective protein nanocarriers, the protein-guided delivery in the infected phagocytic cells allows it to exert its hydrolytic action on the lipid layer of the Mycobacterium.

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Authors and Affiliations

  1. Faculty of Sciences and Technology of the New University of Lisbon, Almada, Portugal

    L. Pereira

  2. Faculty of Pharmacy of the University of Lisbon, Intracellular Trafficking Modulation for Advanced Drug Delivery (InTraCell_ADD) Research Group, iMed.UL - Research Institute for Medicines and Pharmaceutical Sciences, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal

    J. Diogo, R. Mateus, M. Pimentel & M. Videira

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  1. L. Pereira
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  2. J. Diogo
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Correspondence to M. Videira.

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Pereira, L., Diogo, J., Mateus, R. et al. Host-directed strategies using lipid nanoparticles to reduce mycobacteria survival. J Nanopart Res 17, 73 (2015). https://doi.org/10.1007/s11051-015-2892-x

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