title: Aptamer-Dendrimer Bioconjugates for Targeted Delivery of miR-34a Expressing Plasmid and Antitumor Effects in Non-Small Cell Lung Cancer Cells.
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.
authors.affiliation: Department of Respiratory, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China; Department of Respiratory, Qilu Hospital, Shandong University Medical School, Jinan, P.R. China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Clinic of North Sea Fleet of PLA Navy, Qingdao, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Respiratory, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Respiratory, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.
authors.forename: Dunqiang
authors.initials: D
authors.lastname: Ren
authors.affiliation: Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Respiratory, Qilu Hospital, Shandong University Medical School, Jinan, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Jiao
mesh_terms: D052157:Aptamers, Nucleotide / Q000008:administration & dosage / Q000737:chemistry; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D052157:Aptamers, Nucleotide; C000595707:BCL2 protein, human; D050091:Dendrimers; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53