Synthesis and characterization of a dual-targeting, mitochondrial-immobilizing nanoparticle drug delivery system

Loading...
Thumbnail Image

Date

2017-05

Journal Title

Journal ISSN

Volume Title

Publisher

The Ohio State University

Research Projects

Organizational Units

Journal Issue

Abstract

Cancer stem-like cells (CSCs) are rare subpopulations of cells that are drug resistant and have been shown to be responsible for the recurrence of cancer. CSCs are typically not responsive to traditional cancer treatments, so an alternative method, able to overcome the drug resistance of these subpopulations, is desirable. Nanoparticles are one potential solution to this problem and are currently under intense research. The aim of this study was to determine an ideal method (i.e. cheap, quick, and efficient) for synthesizing and loading nanoparticles with therapeutics for treating cancerous cells. A novel nanoprecipitation method was designed to create smaller and more homogeneous particles compared to the traditional nanoprecipitation method. We hypothesized that this method would be able to encapsulate therapeutic agents in Pluronic F127 and poly(L-lactic-co-glycolic acid) that would result in nanoparticles, further coated with triphenylphosphonium and hyaluronic acid for targeting capabilities, less than 200nm in diameter with surface charges below -20mV. Further, we hypothesized this method would result in higher encapsulation efficiencies of therapeutics and be able to target mitochondria in vitro. It was found that infusion rates of 20ml/hr for water and 4ml/hr for oil, a polymer concentration of 10mg/ml, and a 1:1 ratio of PLGA to PF127-TPP resulted in the smallest (168.48±6.3nm), most homogeneous nanoparticles (PDI = 0.05) with surface charges of -35.54±3mV. The encapsulation efficiency for porphyrin was 73.5±3.4%, but was lower for lonidamine and doxorubicin, at 36.3±5.2% and 21.9±15.1%, respectively. Mitochondrial targeting capabilities of the particles were confirmed with PLGA-PF127-TPP-Dox nanoparticles with MDA-MB-231 cells via confocal images and fluorescence overlap of doxorubicin with MitoTracker Deep Red dye. These results indicate that while more studies need to be done to determine drug release mechanisms and kinetics and targeting capabilities of PLGA-PF127-TPP-HA nanoparticles, the novel method described here is viable for creating dual targeting nanoparticles capable of treating drug resistant phenotypes of CSCs.

Description

2017 Denman Undergraduate Research Forum Winner. First Place

Keywords

Citation