Histone Deacetylase Inhibitor (HDACi) Conjugated Polycaprolactone for Combination Cancer Therapy

Biomacromolecules
Ruvanthi N KularatneMihaela C Stefan

Abstract

The short chain fatty acid, 4-phenylbutyric acid (PBA), is used for the treatment of urea cycle disorders and sickle cell disease as an endoplasmic reticulum stress inhibitor. PBA is also known as a histone deacetylase inhibitor (HDACi). We report here the effect of combination therapy on HeLa cancer cells using PBA as the HDACi together with the anticancer drug, doxorubicin (DOX). We synthesized γ-4-phenylbutyrate-ε-caprolactone monomer which was polymerized to form poly(γ-4-phenylbutyrate-ε-caprolactone) (PPBCL) homopolymer using NdCl3·3TEP/TIBA (TEP = triethyl phosphate, TIBA = triisobutylaluminum) catalytic system. DOX-loaded nanoparticles were prepared from the PPBCL homopolymer using poly(ethylene glycol) as a surfactant. An encapsulation efficiency as high as 88% was obtained for these nanoparticles. The DOX-loaded nanoparticles showed a cumulative release of >95% of DOX at pH 5 and 37 °C within 12 h, and PBA release was monitored by 1H NMR spectroscopy. The efficiency of the combination therapy can notably be seen in the cytotoxicity study carried out on HeLa cells, where only ∼20% of cell viability was observed after treatment with the DOX-loaded nanoparticles. This drastic cytotoxic effect on HeLa cells is the result ...Continue Reading

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Citations

Jan 29, 2019·Current Topics in Medicinal Chemistry·Yu BaiGuihua Cui
May 1, 2019·Current Pharmaceutical Biotechnology·Abbas H AzandaryaniTahereh Jamshidnejad-Tosaramandani
Jun 26, 2020·Frontiers in Cell and Developmental Biology·Bin TuYongzhuo Huang
Jun 15, 2021·Journal of Biomaterials Science. Polymer Edition·Donghui ZhangChao Liu

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