title: Aptamer-hybrid nanoparticle bioconjugate efficiently delivers miRNA-29b to non-small-cell lung cancer cells and inhibits growth by downregulating essential oncoproteins.
abstract: MicroRNAs (miRNAs) are potentially attractive candidates for cancer therapy. However, their therapeutic application is limited by lack of availability of an efficient delivery system to stably deliver these potent molecules intracellularly to cancer cells while avoiding healthy cells. We developed a novel aptamer-hybrid nanoparticle bioconjugate delivery system to selectively deliver miRNA-29b to MUC1-expressing cancer cells. Significant downregulation of oncoproteins DNMT3b and MCL1 was demonstrated by these MUC1 aptamer-functionalized hybrid nanoparticles in A549 cells. Furthermore, downregulation of these oncoproteins led to antiproliferative effect and induction of apoptosis in a superior version when compared with Lipofectamine 2000. This novel aptamer-hybrid nanoparticle bioconjugate delivery system could potentially serve as a platform for intracellular delivery of miRNAs to cancer cells, hence improving the therapeutic outcome of lung cancer.
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Maryna
authors.initials: M
authors.lastname: Perepelyuk
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Maher
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Ashakumary
authors.initials: A
authors.lastname: Lakshmikuttyamma
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Sunday A
authors.initials: SA
authors.lastname: Shoyele
mesh_terms: D052157:Aptamers, Nucleotide / Q000008:administration & dosage* / Q000737:chemistry; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D006801:Humans; D008055:Lipids; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics; D018396:Mucin-1 / Q000235:genetics; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D015513:Oncogene Proteins / Q000235:genetics; D000097584:DNA Methyltransferase 3B
chemical_list: D052157:Aptamers, Nucleotide; D004248:DNA (Cytosine-5-)-Methyltransferases; D008055:Lipids; D035683:MicroRNAs; D018396:Mucin-1; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D015513:Oncogene Proteins; D000097584:DNA Methyltransferase 3B; C086724:Lipofectamine; C579095:MCL1 protein, human; C532045:MIRN29a microRNA, human; C060192:MUC1 protein, human
keywords: aptamer; lung cancer; microRNA; nanoparticles; targeted delivery