Folate-linked nanoparticle-mediated suicide gene therapy in human prostate cancer and nasopharyngeal cancer with herpes simplex virus thymidine kinase.
For targeted gene delivery to human prostate cancer LNCaP and PC-3 cells and nasopharyngeal cancer KB cells, we developed a folate-linked nanoparticle (NP-F), and evaluated the potential of NP-F-mediated suicide gene therapy in the cells and xenografts with herpes simplex virus thymidine kinase (HSV-tk) and connexin 43 (Cx43). An NP-F-plasmid DNA complex (NP-F nanoplex) showed high DNA transfection efficiency in KB, LNCaP and PC-3 cells. Cell growth inhibition in the presence of ganciclovir (GCV) was enhanced with HSV-tk and Cx43 genes in LNCaP cells. In suicide gene therapy, the tumor growths of KB and LNCaP xenografts were significantly inhibited when an NP-F nanoplex of the HSV-tk gene, and HSV-tk and Cx43 genes, respectively, was injected intratumorally and GCV was administered intraperitoneally. These findings suggested that the NP-F is a potential target vector in prostate and nasopharyngeal cancer for suicide gene therapy.
Hattori
Yoshiyuki
Y
Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo 142-8501, Japan.
Maitani
Yoshie
Y
D002851:Chromatography, High Pressure Liquid; D018031:Connexin 43 / Q000378:metabolism; D017931:DNA Primers; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005492:Folic Acid / Q000378:metabolism*; D018014:Gene Transfer Techniques; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases; D008297:Male; D049329:Nanostructures; D009303:Nasopharyngeal Neoplasms / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D011471:Prostatic Neoplasms / Q000628:therapy*; D018139:Simplexvirus / Q000235:genetics / Q000378:metabolism*; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*
D018031:Connexin 43; D017931:DNA Primers; D005492:Folic Acid; D008156:Luciferases; D013937:Thymidine Kinase; D016650:Fluorescein-5-isothiocyanate