NT-polyplex: a new tool for therapeutic gene delivery to neuroblastoma tumors.
Neurotensin (NT)-polyplex is a nonviral system for the targeted gene delivery to cells that express and internalize the high-affinity NT receptor (NTSR1). In hemiparkinsonian rats, we previously demonstrated the morphological and functional recovery from dopaminergic neurodegeneration using the NT-polyplex as a vehicle to transfect a neurotrophic gene. The main objective of this work was to demonstrate the feasibility of NT-polyplex to transfect reporter or therapeutic genes into neuroblastoma tumors through the blood stream or by intratumoral injection. N1E-115 cells known to express NTSR1 were allografted into athymic mice to generate the neuroblastoma tumor model. Both routes of administration allowed the NT-polyplex to reach and transfect tumoral cells. A low transgene expression was also detected in intestinal tract cells only after the injection into the blood stream. The transfection of the thymidine kinase (HSVTK) suicide gene followed by ganciclovir (GCV) treatment decreased the size and weight of neuroblastoma tumors by 30-50% and increased apoptosis compared to controls. This study shows the potential of the NT-polyplex as specific gene-transfer system for NTSR1 cancer cells.
Rubio-Zapata
H A
HA
Department of Physiology, Biophysics and Neuroscience, CINVESTAV, Mexico DF, Mexico.
Rembao-Bojorquez
J D
JD
Arango-Rodriguez
M L
ML
Dupouy
S
S
Forgez
P
P
Martinez-Fong
D
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015774:Ganciclovir / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000737:chemistry*; D008297:Male; D051379:Mice; D009447:Neuroblastoma / Q000188:drug therapy / Q000628:therapy*; D009496:Neurotensin / Q000235:genetics / Q000502:physiology*; D010957:Plasmids / Q000737:chemistry; D013937:Thymidine Kinase / Q000235:genetics / Q000502:physiology
D009496:Neurotensin; D013937:Thymidine Kinase; D015774:Ganciclovir