John Garner

PLGA from PolySciTech used in development of iron-chelator nanodelivery system as a treatment for cancer

Blog Post created by John Garner on Sep 4, 2019

An ideal chemotherapeutic would be a compound which is highly toxic towards cancerous cells but relatively benign towards normal (healthy) cells. Most conventional chemotherapeutics (such as paclitaxel, 5FU, docetaxel, etc.) are not so selective and rather present a generic propensity to prevent growth of both cancerous and healthy cells leading to severe side-effects. Research has identified compounds which present limited toxicity against normal cells while maintaining high efficacy against cancer cells. Recently, researchers at University of Houston and The Pennsylvania State University used PLGA (AP023 and AP165) from PolySciTech (www.polyscitech.com) to create nanoparticles for delivery of a novel anticancer chelator compound Dp44mT. This research holds promise to provide a novel means of treating cancer with limited side effects. Read more: Claire K. Holley, You Jung Kang, Chung-Fan Kuo, Mohammad Reza Abidian, Sheereen Majd “Development and In Vitro Assessment of an Anti-Tumor Nano-Formulation” Colloids and Surfaces B: Biointerfaces 2019, 110481 https://www.sciencedirect.com/science/article/pii/S0927776519306253.

 

“Highlights: Iron chelator Dp44mT was efficiently encapsulated in PLGA NPs of 50-120 nm size. Dp44mT-NPs were highly toxic to glioma cell lines, U251 and U87, with IC50 <150 nM. Dp44mT-NPs were not toxic to healthy Astrocyte control cells. Dp44mT-NPs were uptaken by glioma cells and markedly enhanced their apoptosis. Dp44mT-NPs clearly inhibited the growth of U251 glioma spheroids in vitro. Abstract: This study aims to develop a new anti-cancer formulation based on the chelator Dp44mT (Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone). Dp44mT has outstanding anti-tumor activity and the unique ability to overcome multidrug-resistance in cancer cells. This highly toxic compound has thus far only been applied in free form, limiting its therapeutic effectiveness. To reach its full therapeutic potential, however, Dp44mT shoud be encapsulted in a nano-carrier that would enable its selective and controlled delivery to malignant cells. As the first step towards this goal, here we encapsulate Dp44mT in nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA), characterize this nano-formulation, and evaluate its therapeutic potential against cancer cells in vitro. Our results showed that the Dp44mT-loaded NPs were homogenous in shape and size, and had good colloidal stability. These PLGA NPs also showed high encapsulation efficiency and loading capacity for Dp44mT and enabled the sustained and tunable release of this chelator. Dp44mT-NPs were uptaken by cancer cells, showed a strong and dose-dependent cytotoxicity towards these cells, and significantly increased the apoptotic cell death, in both monolayer and spheroid tumor models. This formulation had a low-level of toxicity towards healthy control cells, indicating an inherent selectivity towards malignant cells. These results demonstrate the great potential of this novel Dp44mT-based nano-formulation for the use in cancer therapy. Keywords: PLGA nanoparticles Drug delivery Anti-tumor drug Nano-formulation In vitro study”

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