원문정보
초록
영어
Various RNAi delivery systems have been developed using virus, liposomes and polymer based nanoparticles, but issues like difficulties in production scale up, drug leakage and unwanted toxicity propels the consideration for development of robust vector system of biological origin. In this study, we therefore focused on to development of bacterially derived nano sized outer membrane vesicles (OMVs) for siRNA encapsulation and specifically targeting of cancer cell surface via receptor specific Affibody molecules. For this purpose, HER2 receptor specific Affibody was co-localized on outer membrane of secreted OMVs (HER2-AffiOMVs) with the help of ClyA, a pore forming toxin which shows no cytotoxicity upon fusion and acts as transporter for fusion partners. HER2-AffiOMVs si-KSP treated SKOV3 cells showed a significant KSP gene silencing along with substantial inhibition of KSP protein expression and massive cell death, confirmed by MTT assay. In summary, we developed a novel siRNA carrier of bacterial origin which is inert, rigid and stable therefore can overcome undesirable side effects seen due to cargo leakage. The possibility to re-engineer OMVs and express targeting ligands on their surface makes it suitable carrier system for targeted delivery.