Nucleic acid gated nanopore delivery of antibiotics

Tezin Türü: Doktora

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Edebiyat Fakültesi, Biyolojik Bilimler Bölümü, Türkiye

Tezin Onay Tarihi: 2018




Discovery of new strategies in administration of antimicrobial agents are essential in the ongoing battle against pathogens due to rapidly emerging antimicrobial resistance. Nanotechnology provide unique opportunities in this respect for the development of targeted drug delivery solutions for effective usage of current antibiotics. Mesoporous silica particles are micrometer-sized particles with nanometer-sized porous surface structure. They are advantageous molecules due to small size, biocompatibility, well-defined pore size and modifiable surface. Functional nucleic acids have potential to target the drug loaded nanoparticles. From this perspective, affinity capabilitiy of aptamers and enzymatic cleavage of capability of nucleic acid oligos, targeting of nanoparticles was experimented in this study. Incorporation of Staphylococcus aureus aptamer and an oligo sequence specific to micrococcal nuclease were analysed against the hypothesis that, sealing of drug loaded nanopores with nucleic acids having a function to release the drug in the presence of a specific target, thus increasing the efficiency of drug and decreasing the risk of antibiotic resistance. Staphylococcus epidermidis was used as control organisms and vancomycin was used as antimicrobial drug for proving the specifity of the system. Nanoparticles with cleavega-oriented oligo sealing mechanism decreased the MIC of vancomycin against S. aures strain from 1.061µg/mL to 0.332µg/mL, while affinity-oriented aptamer sealing mechanism functioned with a decreased MIC for S. aures strain from 1.168µg/mL to 0.420µg/mL. In both mechanisms, MIC against Staphylococcus epidermidis increased proving the specifity of antibiotic delivery. The inhibitory performance of proposed targeted drug delivery mechanism proved its potential for further applications and developments.