Feasibility of a subcutaneously administered block/homo-mixed polyplex micelle as a carrier for DNA vaccination in amouse tumor model

被引:22
作者
Cui, Lin [1 ]
Osada, Kensuke [2 ,3 ]
Imaizumi, Akira [1 ]
Kataoka, Kazunori [4 ,5 ]
Nakano, Kenji [1 ]
机构
[1] Kyushu Univ, Innovat Ctr Med Redox Nav, Higashi Ku, Fukuoka 8128582, Japan
[2] Univ Tokyo, Grad Sch Engn, Dept Bioengn, Bunkyo Ku, Tokyo 1130033, Japan
[3] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan
[4] Univ Tokyo, Grad Sch Engn, Dept Mat Engn, Bunkyo Ku, Tokyo 1130033, Japan
[5] Univ Tokyo, Grad Sch Med, Ctr Dis Biol & Integrat Med, Div Clin Biotechnol,Bunkyo Ku, Tokyo 1130033, Japan
关键词
DNA vaccine; Polyplex micelle; Subcutaneous administration; CTL; Tumor rejection immunity; CONTROLLED INTRACELLULAR TRAFFICKING; EPIDERMAL LANGERHANS CELLS; PEGYLATED POLYPLEX; DENDRITIC CELLS; GENE DELIVERY; IN-VIVO; IMMUNIZATION; EXPRESSION; LIPOSOMES; CATIOMER;
D O I
10.1016/j.jconrel.2015.03.029
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
In this study, the potential of DNA vaccine by subcutaneously (s.c.) administered block/homo-mixed (B/H) polyplex micelles carrying genes encoding tumor-associated antigen SART3 as well as CD40L and GM-CSF was compared with the intraperitoneal (i.p.) and intravenous (i.v.) administrations or electroporation method. Confocal laser microscopy revealed high localization of polyplexes in groin lymph nodes and local skin tissues after s.c. administration, and in the mesenteric lymph nodes, liver, and spleen after i.p. administration, but not after i.v. administration. Real-time RT-PCR and immunohistochemistry showed transgene expression in the above organs by s.c. and i.p. administered B/H polyplex micelles, but not by the i.v. administration or electroporation. Polyplex-carried DNA vaccines significantly decreased the weight of subcutaneous CT26 tumors in mice compared to the mock (2.9 +/- 0.8 vs 6.4 +/- 2.6 g, P < 0.05 for s.c.; 3.2 +/- 1.1 vs 4.7 +/- 2.1 g, P < 0.05 for i.p. administration). The survival rate was improved by s.c. administration of the DNA vaccine (P < 0.05) and by the i.p. administered DNA vaccine (P < 0.01) compared with that of the mock controls in mice with peritoneally disseminated CT26 cancer. Such therapeutic effects were not observed by the naked DNA, i.v. administered DNA vaccine or electroporation. CTL and NK cell activities of splenocytes and infiltration of CD11c(+) DCs, and CD4(+) and CD8a(+) T cells into tumor tissueswere upregulated in the s.c. administered DNA vaccine group (P < 0.05), which was consistent with i.p. administration. No abnormal findings in local injection sites, body weight, or blood examinations were observed by s.c. or i.p. administration of polyplex micelles, whereas proinflammatory cytokine production was minimized in visceral organs with the s.c. administered polyplex-carried DNA vaccine. In conclusion, s.c. administration of B/H polyplex micelles may be a safe and useful modality for DNA vaccination. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:220 / 231
页数:12
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