Aptamer-Dendrimer Bioconjugates for Targeted Delivery of miR-34a Expressing Plasmid and Antitumor Effects in Non-Small Cell Lung Cancer Cells |
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| Authors: | Hongmei Wang Xin Zhao Caihong Guo Dunqiang Ren Yandong Zhao Wei Xiao Wenjie Jiao |
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| Affiliation: | 1. Department of Respiratory, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.; 2. Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.; 3. Department of Respiratory, Qilu Hospital, Shandong University Medical School, Jinan, P.R. China.; 4. The Clinic of North Sea Fleet of PLA Navy, Qingdao, P.R. China.; Universidad de Castilla-La Mancha, SPAIN, |
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| Abstract: | Metastasis and drug resistance are major barriers for the treatment of non-small cell lung cancer (NSCLC). To explore new therapeutic options, we successfully encapsulated MicroRNA-34a (miR-34a), a potent endogenous tumor suppressor in NSCLC into S6 aptamer-conjugated dendrimer to form lung cancer-targeted gene delivery nanoparticles (PAM-Ap/pMiR-34a NPs). PAM-Ap/pMiR-34a NPs had a diameter of 100–200 nm and Zeta potential of ~30 mV at applied N/P ratio. The aptamer conjugation significantly improved cellular uptake as well as gene transfection efficiency of PAM-Ap/pMiR-34a NPs in cultured NSCLC cells. We showed that PAM-Ap/pMiR-34a NPs enhanced the regulation of targeted genes, BCL-2 and p53 in vitro. In addition, we revealed PAM-Ap/pMiR-34a NPs significantly inhibited cell growth, migration, invasion and induced apoptosis of lung cancer cells compared with non-targeted NPs. The method provided a novel therapeutic strategy for the experimental treatment of NSCLC. |
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