Recombinant lambda-phage nanobioparticles for tumor therapy in mice models.
Lambda phages have considerable potential as gene delivery vehicles due to their genetic tractability, low cost, safety and physical characteristics in comparison to other nanocarriers and gene porters. Little is known concerning lambda phage-mediated gene transfer and expression in mammalian hosts. We therefore performed experiments to evaluate lambda-ZAP bacteriophage-mediated gene transfer and expression in vitro. For this purpose, we constructed recombinant lambda-phage nanobioparticles containing a mammalian expression cassette encoding enhanced green fluorescent protein (EGFP) and E7 gene of human papillomavirus type 16 (lambda-HPV-16 E7) using Lambda ZAP- CMV XR vector. Four cell lines (COS-7, CHO, TC-1 and HEK-239) were transduced with the nanobioparticles. We also characterized the therapeutic anti-tumor effects of the recombinant lambda-HPV-16 E7 phage in C57BL/6 tumor mice model as a cancer vaccine. Obtained results showed that delivery and expression of these genes in fibroblastic cells (COS-7 and CHO) are more efficient than epithelial cells (TC-1 and HEK-239) using these nanobioparticles. Despite the same phage M.O.I entry, the internalizing titers of COS-7 and CHO cells were more than TC-1 and HEK-293 cells, respectively. Mice vaccinated with lambda-HPV-16 E7 are able to generate potent therapeutic antitumor effects against challenge with E7- expressing tumor cell line, TC-1 compared to group treated with the wild phage. The results demonstrated that the recombinant lambda-phages, due to their capabilities in transducing mammalian cells, can also be considered in design and construction of novel and safe phage-based nanomedicines.
Ghaemi
Amir
A
Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, 14115-111 Iran. soleim_h@modares.ac.ir.
Soleimanjahi
Hoorieh
H
Gill
Pooria
P
Hassan
Zuhair
Z
Jahromi
Soodeh Razeghi M
SR
Roohvand
Farzin
F
J Virol. 2000 Aug;74(15):7127-36
10888653
J Appl Microbiol. 2007 May;102(5):1337-49
17448169
Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):7934-8
1518816
J Transl Med. 2005 Mar 02;3(1):10
15740633
Vaccine. 2004 Apr 16;22(13-14):1666-71
15068849
Expert Opin Drug Deliv. 2007 May;4(3):197-213
17489649
Gene Ther. 2006 Jan;13(1):67-77
16107858
BMC Biotechnol. 2008 Apr 03;8:37
18387177
Biomaterials. 2005 May;26(15):2705-11
15585274
Hum Gene Ther. 2000 Nov 1;11(16):2207-18
11084678
J Virol. 2000 Nov;74(21):10074-80
11024136
Adv Drug Deliv Rev. 2008 May 22;60(8):915-28
18325628
Eur J Immunol. 1999 Mar;29(3):964-72
10092101
Vaccine. 2003 Jun 1;21 Suppl 2:S96-101
12763690
Gene Ther. 2000 Oct;7(19):1613-23
11083469
Microbiol Rev. 1992 Dec;56(4):577-91
1480110
Virology. 2000 Mar 15;268(2):471-81
10704355
Appl Microbiol Biotechnol. 2005 Aug;68(3):346-54
15711794
Biochem J. 2007 Jul 1;405(1):41-9
17355227
Hum Gene Ther. 1997 Sep 20;8(14):1651-8
9322867
Antimicrob Agents Chemother. 2007 Jun;51(6):2156-63
17404004
Curr Opin Mol Ther. 2004 Feb;6(1):40-7
15011780
Vaccine. 2004 Jun 23;22(19):2413-9
15193403
Drugs Today (Barc). 2004 Nov;40(11):913-29
15645004
Curr Drug Deliv. 2005 Oct;2(4):329-40
16305436
FASEB J. 1999 Apr;13(6):727-34
10094933
Expert Opin Drug Deliv. 2005 Mar;2(2):237-54
16296751
Nanomedicine. 2009 Dec;5(4):457-62
19245856
Expert Rev Vaccines. 2009 May;8(5):567-76
19397414
Vaccine. 2004 Nov 25;23(2):258-66
15531045
Virology. 2008 Apr 10;373(2):274-86
18191979