Aptamer-Dendrimer Bioconjugates for Targeted Delivery of miR-34a Expressing Plasmid and Antitumor Effects in Non-Small Cell Lung Cancer Cells

• Published in: PloS one Vol. 10; no. 9; p. e0139136
• Main Authors: Wang, Hongmei, Zhao, Xin, Guo, Caihong, Ren, Dunqiang, Zhao, Yandong, Xiao, Wei, Jiao, Wenjie
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25-09-2015; Public Library of Science (PLoS)
• Subjects: Anticancer properties; Antitumor activity; Apoptosis; Aptamers; Aptamers, Nucleotide - administration & dosage; Aptamers, Nucleotide - chemistry; Bcl-2 protein; Biomarkers; Cancer; Cancer genetics; Cancer therapies; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Care and treatment; Cell cycle; Cell Line, Tumor; Cell migration; Chemotherapy; Complications and side effects; Conjugation; Dendrimers - administration & dosage; Dendrimers - chemistry; Deoxyribonucleic acid; Development and progression; DNA; Drug resistance; Efficiency; Gene expression; Gene regulation; Gene transfer; Genetic aspects; Genetic Therapy - methods; Genetic Vectors - administration & dosage; Genetic Vectors - genetics; Health aspects; Humans; Ligands; Lung cancer; Lung diseases; Metastases; Metastasis; MicroRNA; MicroRNAs - administration & dosage; MicroRNAs - genetics; miRNA; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Non-small cell lung cancer; Non-small cell lung carcinoma; p53 Protein; Penicillin; Polyethylene glycol; Proteins; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Ribonucleic acid; RNA; Thoracic surgery; Transfection; Tumor suppressor genes; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors; Zeta potential; United States; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0139136

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.