Evaluation of MUC1-Aptamer Functionalized Hybrid Nanoparticles for Targeted Delivery of miRNA-29b to Nonsmall Cell Lung Cancer

Mol Pharm. 2018 Mar 5;15(3):985-993. doi: 10.1021/acs.molpharmaceut.7b00900. Epub 2018 Feb 19.

Abstract

The objective of this study was to evaluate the therapeutic efficacy and pharmacokinetic study of mucin1-aptamer functionalized miRNA-29b-loaded hybrid nanoparticles (MAFMILHNs) in lung tumor-bearing SCID mice. MAFMILHNs were manufactured using an isoelectric point based nanotechnology. They were then fully characterized for particle size, loading capacity, zeta potential, and encapsulation efficiency. The ability of MAFMILHNs to downregulate oncoprotein DNMT3B both at the cellular level and in vivo was monitored using Western blot, while the effect of the downregulation of DNMT3B on tumor growth was assessed using bioluminescence. Results indicate that the presence of MUC1-aptamer conjugated to the surface of the nanoparticles enhanced the selective delivery of miRNA-29b to tumor cells and tissues. Further, the downregulation of DNMT3B by MAFMILHNs resulted in the inhibition of tumor growth in mouse models.

Keywords: aptamer; gene-silencing; lung cancer; miRNA-29b; nanomedicine; oncoproteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methyltransferase 3B
  • Down-Regulation / genetics
  • Drug Delivery Systems / methods*
  • Drug Evaluation, Preclinical
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Genetic Therapy / methods*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / therapy*
  • Mice
  • Mice, SCID
  • MicroRNAs / administration & dosage*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Mucin-1 / chemistry
  • Mucin-1 / genetics
  • Nanoparticles / chemistry*
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • Aptamers, Nucleotide
  • MIRN29a microRNA, human
  • MUC1 protein, human
  • MicroRNAs
  • Mucin-1
  • DNA (Cytosine-5-)-Methyltransferases