A microsphere-liposome (microplex) vector for targeted gene therapy of cancer. II. In vivo biodistribution study in a solid tumor model.
Cationic liposomes are commonly used for transfection of plasmids into mammalian cells, while microspheres have been traditionally used for selective delivery of anticancer agents into tumor vasculature. We have developed a novel vector, comprised of cationic liposomes electrostatically bound to ion-exchange microspheres (termed 'microplex') for targeted gene therapy of solid tumors. The delivery modes tested in a rat solid tumor model were free plasmids, plasmids bound to microspheres, to liposomes, or to the combination vector. The greatest amount of chloramphenicol acetyltransferase (CAT) reporter gene expression in tumors was achieved using the microplex vector; 3.4-fold compared with free, and 1.8-fold compared with both microspherical and liposomal deliveries (p < 0.01). Tumor-to-normal kidney tissue CAT expression ratios were as follows: free 1.9:1; microspherical 3.7:1; liposomal 1.4:1 and microplexical 2.7:1. Expression between the two types of tissues was significantly different (p < 0.01) for all delivery modes. Microspheres targeted the plasmids to the tumors, while the action of cationic liposomes on cellular membranes allowed more plasmids to breach the cell membrane. This study has proven that the novel microplex vector is capable of selective delivery of genes to tumors and has the potential to target genes in clinical trials.
Dass
C R
CR
School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, Australia. cdass@medau.jnj.com
Walker
T L
TL
Kalle
W H
WH
Burton
M A
MA
D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D003587:Cytomegalovirus / Q000235:genetics; D004337:Drug Carriers; D018390:Gene Targeting / Q000379:methods*; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007680:Kidney Neoplasms / Q000737:chemistry / Q000201:enzymology; D008081:Liposomes; D008863:Microspheres; D009369:Neoplasms / Q000201:enzymology / Q000628:therapy*; D010957:Plasmids; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
D004337:Drug Carriers; D008081:Liposomes; D015500:Chloramphenicol O-Acetyltransferase