Thioaptamer targeted discoidal microparticles increase self immunity and reduce Mycobacterium tuberculosis burden in mice
| Autor: | Ngan P. Ha, Jinyun Yuan, Fransisca Leonard, Edward A. Graviss, Ganesh L.R. Lokesh, David G. Gorenstein, Xuewu Liu, Jenolyn F. Alexander, Soumya Chatterjee, Jeffrey D. Cirillo, David E. Volk, Biana Godin, Preeti Sule |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Silicon Cellular immunity Tuberculosis T-Lymphocytes medicine.medical_treatment Pharmaceutical Science Mycobacterium tuberculosis 03 medical and health sciences In vivo Immunity medicine Animals Humans Macrophage Lung Cells Cultured Drug Carriers Mice Inbred BALB C biology Macrophages Aptamers Nucleotide biology.organism_classification medicine.disease Hyaluronan Receptors 030104 developmental biology medicine.anatomical_structure Immunology Female Adjuvant |
| Zdroj: | Journal of Controlled Release. 266:238-247 |
| ISSN: | 0168-3659 |
| DOI: | 10.1016/j.jconrel.2017.09.038 |
| Popis: | Worldwide, tuberculosis (TB) remains one of the most prevalent infectious diseases causing morbidity and death in >1.5 million patients annually. Mycobacterium tuberculosis (Mtb), the etiologic agent of TB, usually resides in the alveolar macrophages. Current tuberculosis treatment methods require more than six months, and low compliance often leads to therapeutic failure and multidrug resistant strain development. Critical to improving TB-therapy is shortening treatment duration and increasing therapeutic efficacy. In this study, we sought to determine if lung hemodynamics and pathological changes in Mtb infected cells can be used for the selective targeting of microparticles to infected tissue(s). Thioaptamers (TA) with CD44 (CD44TA) targeting moiety were conjugated to discoidal silicon mesoporous microparticles (SMP) to enhance accumulation of these agents/carriers in the infected macrophages in the lungs. In vitro, CD44TA-SMP accumulated in macrophages infected with mycobacteria efficiently killing the infected cells and decreasing survival of mycobacteria. In vivo, increased accumulations of CD44TA-SMP were recorded in the lung of M. tuberculosis infected mice as compared to controls. TA-targeted carriers significantly diminished bacterial load in the lungs and caused recruitment of T lymphocytes. Proposed mechanism of action of the designed vector accounts for a combination of increased uptake of particles that leads to infected macrophage death, as well as, activation of cellular immunity by the TA, causing increased T-cell accumulation in the treated lungs. Based on our data with CD44TA-SMP, we anticipate that this drug carrier can open new avenues in TB management. |
| Databáze: | OpenAIRE |
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