Gallium nanoparticles facilitate phagosome maturation and inhibit growth of virulent Mycobacterium tuberculosis in macrophages.

Authors

Seoung-Ryoung Choi, University of Nebraska Medical CenterFollow
Bradley E. Britigan, University of Nebraska Medical CenterFollow
David M. Moran, University of Nebraska Medical CenterFollow
Prabagaran Narayanasamy, University of Nebraska Medical Center, OmahaFollow

Document Type

Article

Journal Title

PLoS One

Publication Date

Winter 1-1-2017

Volume

12

Abstract

New treatments and novel drugs are required to counter the growing problem of drug-resistant strains of Mycobacterium tuberculosis (M.tb). Our approach against drug resistant M.tb, as well as other intracellular pathogens, is by targeted drug delivery using nanoformulations of drugs already in use, as well as drugs in development. Among the latter are gallium (III) (Ga)-based compounds. In the current work, six different types of Ga and rifampin nanoparticles were prepared in such a way as to enhance targeting of M.tb infected-macrophages. They were then tested for their ability to inhibit growth of a fully pathogenic strain (H37Rv) or a non-pathogenic strain (H37Ra) of M.tb. Encapsulating Ga in folate- or mannose-conjugated block copolymers provided sustained Ga release for 15 days and significantly inhibited M.tb growth in human monocyte-derived macrophages. Nanoformulations with dendrimers encapsulating Ga or rifampin also showed promising anti-tuberculous activity. The nanoparticles co-localized with M.tb containing phagosomes, as measured by detection of mature cathepsin D (34 kDa, lysosomal hydrogenase). They also promoted maturation of the phagosome, which would be expected to increase macrophage-mediated killing of the organism. Delivery of Ga or rifampin in the form of nanoparticles to macrophages offers a promising approach for the development of new therapeutic anti-tuberculous drugs.

DOI Link

10.1371/journal.pone.0177987

ISSN

1932-6203

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Choi, Seoung-Ryoung; Britigan, Bradley E.; Moran, David M.; and Narayanasamy, Prabagaran, "Gallium nanoparticles facilitate phagosome maturation and inhibit growth of virulent Mycobacterium tuberculosis in macrophages." (2017). Journal Articles: Pathology and Microbiology. 59.
https://digitalcommons.unmc.edu/com_pathmicro_articles/59