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.