Antibody Modified Nanoparticle-Mediated Delivery of miR-124 Regulates Apoptosis via Repression the Stat3 Signal in Mycobacterial-Infected Microglia.

The mechanism of Mycobacterium tuberculosis ( M.tb ) evasion of host cell remains elusive. Several microRNAs that are involved in this complex process were identified. miRNA interference-based therapeutics represents an attractive challenge and shows huge potential for disorder treatment. In this study, we found that miR-124-3p expression is significantly decreased in microglia after Mycobacterium marinum ( M.m ) infection. To achieve better target transfection effect, a CD11b antibody and PEI modified nanoparticles-based Nano platform had been developed. This system was equipped by conjugation of miRNA-124-3p onto the surface of nanoparticles with a PEI/CD11b antibody coating. Transfection with miR-124-3p promoted microglia apoptosis through upregulation of Caspase3 or downregulation of Bcl-2 and Bcl-xl. More importantly, transfection with miR-124-3p inhibitor increases the mycobacterium proliferation in microglia. Based on the above, we further found miRNA-124-3p to bind to 3'untranslated region of Stat3, resulting in the downregulation of its protein to trigger cells apoptosis through Stat3-related pathway. As such, our research might provide new insights towards target delivering miRNA through the bold-brain barrier (BBB) and exploiting highly effective anti-tuberculous meningitis drugs. Taken together, our findings suggest how Mycobacterium can manipulate host miRNA expression to regulate cell survival for its own proliferation, and highlight the importance to develop novel therapeutic strategies against tuberculous meningitis.