Combination of adenovirus and cross-linked low molecular weight PEI improves efficiency of gene transduction.
Recombinant adenovirus (Ad)-mediated gene therapy is an exciting novel strategy in cancer treatment. However, poor infection efficiency with coxsackievirus and adenovirus receptor (CAR) down-regulated cancer cell lines is one of the major challenges for its practical and extensive application. As an alternative method of viral gene delivery, a non-viral carrier using cationic materials could compensate for the limitation of adenovirus. In our study, adenovectors were complexed with a new synthetic polymer PEI-DEG-bis-NPC (PDN) based on polyethylenimine (PEI), and then the properties of the vehicle were characterized by measurement of size distribution, zeta potential and transmission electron microscopy (TEM). Enhancement of gene transduction by Ad/PDN complexes was observed in both CAR-overexpressing cell lines (A549) and CAR-lacking cell lines (MDCK, CHO, LLC), as a result of facilitating binding and cell uptake of adenoviral particles by the cationic component. Ad/PDN complexes also promoted the inhibition of tumor growth in vivo and prolonged the survival time of tumor-bearing mice. These data suggest that a combination of viral and non-viral gene delivery methods may offer a new approach to successful cancer gene therapy.
Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.
Jianfeng
J
Han
Dong
D
Zhao
Zhirong
Z
Zhong
Zhirong
Z
Zhang
Tao
T
Gong
Xun
X
Sun
D000256:Adenoviridae / Q000737:chemistry* / Q000235:genetics* / Q000648:ultrastructure; D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000235:genetics / Q000502:physiology; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D004285:Dogs; D005822:Genetic Vectors / Q000009:adverse effects / Q000737:chemistry* / Q000235:genetics* / Q000648:ultrastructure; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D008970:Molecular Weight; D009369:Neoplasms / Q000628:therapy; D011094:Polyethyleneimine / Q000009:adverse effects / Q000737:chemistry*; D014161:Transduction, Genetic / Q000379:methods*
D054377:Chemokine CXCL12; D011094:Polyethyleneimine