Document Type
Article
Publication Date
3-21-2021
Department
Department of Chemical Engineering
Abstract
In the area of gene-directed enzyme prodrug therapy (GDEPT), using herpes simplex virus thymidine kinase (HSV-tk) paired with prodrug ganciclovir (GCV) for cancer treatment has been extensively studied. It is a process involved with two steps whereby the gene (HSV-tk) is first delivered to malignant cells. Afterward, non-toxic GCV is administered to that site and activated to cytotoxic ganciclovir triphosphate by HSV-tk enzyme expressed exogenously. In this study, we presented a one-step approach that both gene and prodrug were delivered at the same time by incorporating them with polymeric micellar nanovectors. GCV was employed as an initiator in the ring-opening polymerization of ε-caprolactone (ε-CL) to synthesize hydrophobic GCV-poly(caprolactone) (GCV-PCL), which was furthered grafted with hydrophilic chitosan to obtain amphiphilic polymer (GCV-PCL-chitosan) for the fabrication of self-assembled micellar nanoparticles. The synthesized amphiphilic polymer was characterized using Fourier transform infrared spectroscopy and proton nuclear magnetic resonance. Micellar prodrug nanoparticles were analyzed by dynamic light scattering, zeta potential, critical micelle concentration, and transmission electron microscopy. Polymeric prodrug micelles with optimal features incorporated with HSV-tk encoding plasmids were cultivated with HT29 colorectal cancer cells and anticancer effectiveness was determined. Our results showed that prodrug GCV and HSV-tk cDNA encoded plasmid incorporated in GCV-PCL-chitosan polymeric nanocarriers could be delivered in a one-step manner to HT-29 cells and triggered high cytotoxicity.
Publication Title
Molecules (Basel, Switzerland)
Recommended Citation
Sawdon, A.,
Zhang, J.,
Peng, S.,
Alyami, E.,
&
Peng, C.
(2021).
Polymeric Nanovectors Incorporated with Ganciclovir and HSV-tk Encoding Plasmid for Gene-Directed Enzyme Prodrug Therapy.
Molecules (Basel, Switzerland),
26(6).
http://doi.org/10.3390/molecules26061759
Retrieved from: https://digitalcommons.mtu.edu/michigantech-p/14811
Version
Publisher's PDF
Publisher's Statement
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Publisher’s version of record: https://doi.org/10.3390/molecules26061759