The emergence of multidrug-resistance represents the main cause of the current status of Tuberculosis (TB) as a major global health problem. The most intriguing property of Mycobacteria which is considered the main obstacle in formulating a rational design of antimycobacterial drug is represented by the capacity of such bacteria to survive and multiply inside the macrophages, this "phagocyte-sabotage" ensuring not only the avoidance of both innate and acquired immune system but also provide a way of systemic dissemination, a cause of clinical relapse and selection of aggressive strains with antibiotic resistance. We propose to develop a gold-silver alloy based bio-nanostructure (Au-AgNP) designed by functionalization with the polysaccharide-mannan for intra-macrophage targeted therapy of Mycobacterium tuberculosis complex (MtbC) infections. Employing the selective recognition of the mannan by the mannose receptor, primarily expressed on the surface of macrophage-family cells, we hypothesize that the Mannan-coated Au-Ag construct will improve the local availability of nanoparticle and enhance the mycobactericidal effect of AgNP and AuNP, nanoparticles which already show promising results in tuberculosis therapy. To assure the best report between antimycobacterial efficiency and the cytotoxic activity, ascending molar concentration of Au in the molecule and increasing doses of Au-AgNP, will be tested on M. tuberculosis cultures and in Mtb infected macrophages.

​