Development of non-viral vector for cancer gene therapy.
Cancer gene therapy has been intensively developed using non-viral vectors, among which cationic liposomes and nanoparticles are the most investigated. Optimal gene therapy for tumors must deliver plasmid DNA (pDNA) or synthetic small interfering RNA (siRNA) to tumor cells with high efficiency and minimal toxicity. We developed new cationic nanoparticles (NP) composed of cholesteryl-3beta-carboxyamidoethylene-N-hydroxyethylamine (OH-Chol) and Tween 80, and evaluated the transfection efficiencies of pDNA and siRNA into human prostate tumor PC-3 xenografts. NP showed effective transfection of pDNA and siRNA when directly injected into the xenografts. For targeted delivery to tumors, vitamin folic acid has been utilized for folate receptor (FR)-mediated drug delivery since FR is frequently overexpressed on many types of human tumors. We developed folate-linked nanoparticles (NP-F) composed of OH-Chol, Tween 80 and folate-poly(ethylene glycol)-distearoylphosphatidylethanolamine conjugate. Tumor growth of FR-positive human nasopharyngeal tumor KB xenografts was significantly inhibited when a complex of NP-F and a therapeutic gene was intratumorally injected. These findings suggested that cationic cholesterol-based nanoparticles are potential non-viral pDNA and siRNA vectors for local tumor treatment.
Hattori
Yoshiyuki
Y
Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, tokyo, Japan. yhattori@hosshi.ac.jp
D002352:Carrier Proteins; D002412:Cations; D002784:Cholesterol / Q000031:analogs & derivatives; D004247:DNA / Q000008:administration & dosage; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008081:Liposomes; D053758:Nanoparticles; D009369:Neoplasms / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D011136:Polysorbates; D034741:RNA, Small Interfering / Q000008:administration & dosage; D011956:Receptors, Cell Surface; D014162:Transfection
D002352:Carrier Proteins; D002412:Cations; D058973:Folate Receptors, GPI-Anchored; D008081:Liposomes; D011136:Polysorbates; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; C551595:cholesteryl-3beta-carbosyamidoethylene-N-hydroxyethylamine; D004247:DNA; D005492:Folic Acid; D002784:Cholesterol