Efficient inhibition of C-26 colon carcinoma by VSVMP gene delivered by biodegradable cationic nanogel derived from polyethyleneimine.
Biodegradable cationic nanoparticles have promising application as a gene delivery system. In this article, heparin-polyethyleneimine (HPEI) nanogels were prepared, and these nanogels were developed as a nonviral gene vector. The transfection efficiency of HPEI nanogels was comparable with that of PEI25K, while the cytotoxicity was lower than that of PEI2K and much lower than that of PEI25K in vitro. These HPEI nanogels also had better blood compatibility than PEI25K. After intravenous administration, HPEI nanogels degraded, and the degradation products were excreted through urine. The plasmid expressing vesicular stomatitis virus matrix protein (pVSVMP) could be efficiently transfected into C-26 colon carcinoma cells by HPEI nanogels in vitro, inhibiting the cell proliferation through apoptosis induction. Intraperitoneal injection of pVSVMP/HPEI complexes efficiently inhibited the abdominal metastases of C-26 colon carcinoma through apoptosis induction (mean tumor weight in mice treated with pVSVMP/HPEI complex = 0.93 g and in control mice = 3.28 g, difference = 2.35 g, 95% confidence interval [CI] = 1.75-2.95 g, P < 0.001) and prolonged the survival of treated mice. Moreover, intravenous application of pVSVMP/HPEI complexes also inhibited the growth of pulmonary metastases of C-26 colon carcinoma through apoptosis induction. The HPEI nanogels delivering pVSVMP have promising application in treating colon carcinoma.
Gou
MaLing
M
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, People's Republic of China.
Men
Ke
K
Zhang
Juan
J
Li
YuHua
Y
Song
Jia
J
Luo
Shan
S
Shi
HuaShan
H
Wen
YanJun
Y
Guo
Gang
G
Huang
MeiJuan
M
Zhao
Xia
X
Qian
ZhiYong
Z
Wei
YuQuan
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000628:therapy*; D005782:Gels / Q000737:chemistry*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D036103:Nanotechnology / Q000379:methods*; D011094:Polyethyleneimine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018116:Vesiculovirus / Q000235:genetics*; D014763:Viral Matrix Proteins / Q000235:genetics*
D000970:Antineoplastic Agents; D005782:Gels; D014763:Viral Matrix Proteins; D011094:Polyethyleneimine