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

Hongmei Wang; Xin Zhao; Caihong Guo; Dunqiang Ren; Yandong Zhao; Wei Xiao; Wenjie Jiao

doi:10.1371/journal.pone.0139136

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

PLoS One. 2015 Sep 25;10(9):e0139136. doi: 10.1371/journal.pone.0139136. eCollection 2015.

Authors

Hongmei Wang¹, Xin Zhao², Caihong Guo³, Dunqiang Ren³, Yandong Zhao⁴, Wei Xiao⁵, Wenjie Jiao⁴

Affiliations

¹ 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.
² The Clinic of North Sea Fleet of PLA Navy, Qingdao, P.R. China.
³ Department of Respiratory, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.
⁴ Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, P.R. China.
⁵ Department of Respiratory, Qilu Hospital, Shandong University Medical School, Jinan, P.R. China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aptamers, Nucleotide / administration & dosage
Aptamers, Nucleotide / chemistry
Carcinoma, Non-Small-Cell Lung / genetics
Carcinoma, Non-Small-Cell Lung / metabolism*
Cell Line, Tumor
Dendrimers / administration & dosage
Dendrimers / chemistry
Genetic Therapy / methods*
Genetic Vectors / administration & dosage
Genetic Vectors / genetics
Humans
MicroRNAs / administration & dosage*
MicroRNAs / genetics
Nanoparticles / administration & dosage*
Nanoparticles / chemistry
Proto-Oncogene Proteins c-bcl-2 / genetics
Proto-Oncogene Proteins c-bcl-2 / metabolism
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism

Substances

Aptamers, Nucleotide
BCL2 protein, human
Dendrimers
MIRN34 microRNA, human
MicroRNAs
Proto-Oncogene Proteins c-bcl-2
TP53 protein, human
Tumor Suppressor Protein p53

Grants and funding

This research was supported by Science and Technology Development Plan Project of Shandong Province (2013WS0273). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.