Combinatorial ligand-directed lung targeting.
Phage display of random peptide libraries is a powerful, unbiased method frequently used to discover ligands for virtually any protein of interest and to reveal functional protein-protein interaction partners. Moreover, in vivo phage display permits selection of peptides that bind specifically to different vascular beds without any previous knowledge pertaining to the nature of their corresponding receptors. Vascular targeting exploits molecular differences inherent in blood vessels within given organs and tissues, as well as diversity between normal and angiogenic blood vessels. Over the years, our group has identified phage capable of homing to lung blood vessels based on screenings using immortalized lung endothelial cells combined with in vivo selections after intravenous administration of combinatorial libraries. Peptides targeting lung vasculature have been extensively characterized and a lead homing peptide has shown interesting biological properties, bringing novel insights as to the implications of lung endothelial cell apoptosis in the pathogenesis of emphysema. We have also designed and developed targeted nanoparticles with imaging capabilities and/or drug delivery functions by combining phage display technology and elemental gold (Au) nanoparticles, constituting a promising platform for the development of therapeutic agents for imaging and treatment of lung disorders. Given the important role of the endothelium in the pathogenesis and progression of several diseases associated with the airways, ligand-directed discovery of lung vascular markers is an important milestone toward the development of future targeted therapies.
Giordano
Ricardo J
RJ
University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd-1374, Houston, TX 77030, USA.
Edwards
Julianna K
JK
Tuder
Rubin M
RM
Arap
Wadih
W
Pasqualini
Renata
R
D000818:Animals; D020650:Combinatorial Chemistry Techniques; D004730:Endothelium, Vascular / Q000033:anatomy & histology*; D006801:Humans; D008024:Ligands; D008168:Lung / Q000098:blood supply* / Q000473:pathology*; D036103:Nanotechnology; D019151:Peptide Library; D011656:Pulmonary Emphysema / Q000175:diagnosis* / Q000628:therapy; D012137:Respiratory System
D008024:Ligands; D019151:Peptide Library
Nat Biotechnol. 2000 Nov;18(11):1185-90
11062439
Am J Physiol. 1999 Jan;276(1):L41-50
9887054
FASEB J. 2006 May;20(7):979-81
16581960
Expert Opin Drug Deliv. 2005 Sep;2(5):909-26
16296786
J Biol Chem. 1999 Apr 23;274(17):11593-8
10206967
J Appl Physiol (1985). 2004 Oct;97(4):1559-66; discussion 1549
15208295
Am J Pathol. 2005 Feb;166(2):625-36
15681844
J Biol Chem. 2008 Oct 24;283(43):29447-60
18718906
Curr Opin Chem Biol. 2002 Jun;6(3):399-404
12023122
Nat Rev Drug Discov. 2007 Apr;6(4):273-86
17396134
Curr Top Dev Biol. 2004;64:73-99
15563945
Science. 2001 Oct 19;294(5542):559-63
11577199
Nature. 1996 Mar 28;380(6572):364-6
8598934
Circ Res. 2006 Feb 3;98(2):159-62
16456105
Science. 2001 Oct 19;294(5542):564-7
11577200
Microvasc Res. 2004 Mar;67(2):139-51
15020205
Dev Dyn. 2000 Feb;217(2):159-69
10706140
Proc Am Thorac Soc. 2008 Sep 15;5(7):763-6
18757314
Curr Drug Targets Inflamm Allergy. 2005 Dec;4(6):665-73
17305522
Trends Cardiovasc Med. 2008 May;18(4):126-32
18555185
Thorax. 2008 May;63(5):463-9
18443163
Science. 1998 Jan 16;279(5349):377-80
9430587
Cancer Res. 2004 Jan 15;64(2):435-9
14744752
Methods Mol Biol. 2007;357:385-406
17172704
Nat Med. 2005 May;11(5):491-8
15852018
Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5096-100
1711218
PLoS One. 2008 May 21;3(5):e2242
18493583
Cancer Res. 2003 Jun 1;63(11):2971-6
12782605
Nat Med. 2001 Nov;7(11):1249-53
11689892
Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10623-8
12963823
Adv Drug Deliv Rev. 2006 Dec 30;58(15):1622-54
17123658
Cell. 2006 Apr 21;125(2):385-98
16630824
J Clin Invest. 1998 Jul 15;102(2):430-7
9664085
Nat Med. 1999 Sep;5(9):1032-8
10470080
J Biol Chem. 1998 Sep 11;273(37):24207-15
9727044
Nat Med. 2002 Feb;8(2):121-7
11821895
Nat Med. 2005 Nov;11(11):1145-9
16270065
Curr Opin Allergy Clin Immunol. 2008 Feb;8(1):44-8
18188017
Am J Respir Cell Mol Biol. 2003 May;28(5):551-4
12707010
Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4471-6
18337507
J Biol Chem. 2001 Jul 6;276(27):25438-46
11320086
Proc Am Thorac Soc. 2008 Sep 15;5(7):783-91
18757318
Nat Biotechnol. 2007 Mar;25(3):327-37
17334358
Am J Respir Cell Mol Biol. 2003 Jul;29(1):88-97
12600822
J Clin Invest. 2000 Dec;106(11):1311-9
11104784
J Clin Invest. 2004 Nov;114(9):1248-59
15520857
Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1215-20
16434473
Cancer. 2009 Jan 1;115(1):128-39
19090007
Methods Enzymol. 2008;445:83-106
19022056
Mol Cell Biochem. 2003 Apr;246(1-2):3-11
12841336
Am J Respir Crit Care Med. 2001 Nov 15;164(10 Pt 2):S39-45
11734465
Nat Med. 2004 Jun;10(6):625-32
15133506