We report the development of new assays and drug delivery systems based on the selective targeting of trehalose for mycobacteria. Trehalose is a key component of the mycobacterial cell wall as well as the cytosol. The mycobacterium uses trehalose as an osmoprotectant and produces various trehalose-containing glycolipids in its cell wall, which are essential for its growth and proliferation. Trehalose dimycolate is proposed to be possibly involved in cell infection by specifically interacting with macrophage inducible C-type lectin (Mincle). We found that trehalose-functionalized nanoparticles interacted strongly with M. smegmatis. Furthermore, the trehalose-functionalized nanoparticles selectively targeted M. smegmatis in the presence of mammalian cells. This opens up opportunities to develop trehalose-functionalized nanomaterials for diagnosis and therapeutics. We synthesized trehalose-grafted multivalent glycopolymers based on biodegradable poly(lactic acid) (PLA), and encapsulated iron oxide magnetic nanoparticles to give stable micelles. When the magnetic micelles were treated with Mycobacterium smegmatis, orange clusters were observed resulting from the interactions between the magnetic micelles and the mycobacteria. Very little particle interaction was found on Staphylococcus epidermidis or E. coli. Furthermore, we synthesized trehalose-functionalized hollow spherical and oblate mesoporous silica nanoparticles which showed high drug loading capacities and sustained drug release profiles. We demonstrated that trehalose-conjugated mesoporous silica nanoparticles increased the antibacterial activity of INH.

Trehalose-grafted glycopolymers and glyconanomaterials for the detection and drug delivery to mycobacteria

253rd National Meeting (2017)

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