Codelivery of Genistein and miRNA-29b to A549 Cells Using Aptamer-Hybrid Nanoparticle Bioconjugates.

Koita Sacko,Sunday A Shoyele,Karthik Thangavel

doi:10.3390/nano9071052

Koita Sacko, Sunday A Shoyele + Show 1 more

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https://doi.org/10.3390/nano9071052

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Journal: Nanomaterials	Publication Date: Jul 23, 2019
Citations: 35	License type: CC BY 4.0

Affiliation: Thomas Jefferson University

Abstract

This study aimed to evaluate the anti-cancer effect of a combination therapy of miRNA-29b and genistein loaded in mucin-1 (MUC 1)-aptamer functionalized hybrid nanoparticles in non-small cell lung cancer (NSCLC) A549 cell line. Genistein-miRNA-29b-loaded hybrid nanoparticles (GMLHN) was prepared and characterized. Particle size and zeta potential were measured using photon correlation spectroscopy (PCS). Encapsulation efficiency and loading efficiency were determined using HPLC. Preferential internalization of MUC 1-aptamer functionalized GMLHN by A549 cells was evaluated and compared to normal MRC-5 cells. The ability of GMLHN to downregulate targeted oncoproteins Phosphorylated protein kinase, strain AK, Thymoma (Phosphorylated protein kinase B) (pAKT), Phosphorylated phosphoinositide 3-kinase (p-PI3K), DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) and Myeloid Cell Leukemia Sequence 1 (MCL 1) was evaluated using western blot, while antiproliferative effect and ability to initiate apoptosis was also assessed in A549 cells. MUC 1-aptamer functionalized GMLHN nanoparticles were prepared. These nanoparticles were preferentially internalized by A549 cells but less so, in MRC-5 cells. pAKT, p-PI3K, DNMT3B and MCL 1 were efficiently downregulated by these nanoparticles without affecting the levels of AKT and PI3K in A549 cells. GMLHN demonstrated a superior antiproliferative effect compared to individual genistein and miRNA-29b-loaded nanoparticles. Results generated were able to demonstrate that genistein-miRNA-29b-loaded hybrid nanoparticles (GMLHN) could be a potential treatment modality for NSCLC because of the ability of the payloads to attack multiple targets.

Highlights

The leading cause of cancer death is non-small cell lung cancer (NSCLC)
Our present study aims to co-encapsulate miRNA-29b with genistein in hybrid nanoparticles (GMLHN) to produce a combination therapy that will effectively treat NSCLC
Fourier Transform-infrared Spectroscopy (FT-IR) spectra in Figure 1B demonstrate the differences in the spectra of both MUC 1-aptamer functionalized Genistein-miRNA-29b-loaded hybrid nanoparticles (GMLHN) and unfunctionalized GMLHN

Summary

Introduction

The leading cause of cancer death is non-small cell lung cancer (NSCLC). In the United states, only a five-year survival rate of 15% has been achieved for all stages of NSCLC [1,2]. Recent breakthroughs in the development of chemotherapy has not reflected significantly in cure rates, which still stands at less than 18% [3]. Resistance of cancer cells to chemotherapy has led to limited efficacy of conventional chemotherapy [3,4,5]. The investment of several billions of dollars in research on cancer drug development has not had any substantial decrease in mortality for several decades [6]. There is a need to try different modalities, to help improve the outcome of chemotherapy in NSCLC

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