title: An integrated approach for the rational design of nanovectors for biomedical imaging and therapy.
abstract: The use of nanoparticles for the early detection, cure, and imaging of diseases has been proved already to have a colossal potential in different biomedical fields, such as oncology and cardiology. A broad spectrum of nanoparticles are currently under development, exhibiting differences in (i) size, ranging from few tens of nanometers to few microns; (ii) shape, from the classical spherical beads to discoidal, hemispherical, cylindrical, and conical; (iii) surface functionalization, with a wide range of electrostatic charges and biomolecule conjugations. Clearly, the library of nanoparticles generated by combining all possible sizes, shapes, and surface physicochemical properties is enormous. With such a complex scenario, an integrated approach is here proposed and described for the rational design of nanoparticle systems (nanovectors) for the intravascular delivery of therapeutic and imaging contrast agents. The proposed integrated approach combines multiscale/multiphysics mathematical models with in vitro assays and in vivo intravital microscopy (IVM) experiments and aims at identifying the optimal combination of size, shape, and surface properties that maximize the nanovectors localization within the diseased microvasculature.
authors.affiliation: Department of Nanomedicine and Biomedical Engineering, The University of Texas Health Science Center, Houston, Texas, USA.
authors.forename: Biana
authors.initials: B
authors.lastname: Godin
authors.forename: Wouter H P
authors.initials: WH
authors.lastname: Driessen
authors.forename: Bettina
authors.initials: B
authors.lastname: Proneth
authors.forename: Sei-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Srimeenakshi
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Rolando
authors.initials: R
authors.lastname: Rumbaut
authors.forename: Wadih
authors.initials: W
authors.lastname: Arap
authors.forename: Renata
authors.initials: R
authors.lastname: Pasqualini
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.forename: Paolo
authors.initials: P
authors.lastname: Decuzzi
mesh_terms: D003952:Diagnostic Imaging / Q000379:methods*; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D010316:Particle Size; D013499:Surface Properties
references.citation: Clin Cancer Res. 1999 Jan;5(1):83-94
references.pmid: 9918206
references.citation: J Biomech. 2008 Jul 19;41(10):2312-8
references.pmid: 18571181
references.citation: Pharm Res. 2009 Jan;26(1):235-43
references.pmid: 18712584
references.citation: J Control Release. 2000 Mar 1;65(1-2):271-84
references.pmid: 10699287
references.citation: FASEB J. 2009 Oct;23(10):3361-7
references.pmid: 19535683
references.citation: Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1526-35
references.pmid: 17526647
references.citation: Microcirculation. 2004 Apr-May;11(3):239-47
references.pmid: 15280078
references.citation: Cancer Res. 1998 Aug 1;58(15):3320-30
references.pmid: 9699662
references.citation: Adv Drug Deliv Rev. 2000 Sep 30;43(2-3):101-64
references.pmid: 10967224
references.citation: Nat Nanotechnol. 2007 Dec;2(12):751-60
references.pmid: 18654426
references.citation: Biomaterials. 2008 Jan;29(3):377-84
references.pmid: 17936897
references.citation: Clin Pharmacokinet. 2006;45(10):965-88
references.pmid: 16984211
references.citation: Annu Rev Biomed Eng. 1999;1:241-63
references.pmid: 11701489
references.citation: Am J Physiol. 1998 Jun;274(6):H2018-24
references.pmid: 9841528
references.citation: Microvasc Res. 1984 Mar;27(2):204-22
references.pmid: 6708830
references.citation: Curr Drug Deliv. 2005 Oct;2(4):369-81
references.pmid: 16305440
references.citation: Clin Cancer Res. 2008 Feb 1;14(3):731-41
references.pmid: 18245533
references.citation: Targeted Diagn Ther. 1990;3:3-22
references.pmid: 2131014
references.citation: J Biomech. 2009 Aug 25;42(12):1885-90
references.pmid: 19523635
references.citation: Trends Cardiovasc Med. 2006 Apr;16(3):80-8
references.pmid: 16546688
references.citation: Am J Physiol Heart Circ Physiol. 2000 Oct;279(4):H2017-23
references.pmid: 11009493
references.citation: Nat Rev Cancer. 2002 Oct;2(10):750-63
references.pmid: 12360278
references.citation: Nat Nanotechnol. 2008 Mar;3(3):151-7
references.pmid: 18654487
references.citation: Clin Cancer Res. 2002 Apr;8(4):1172-81
references.pmid: 11948130
references.citation: Crit Rev Ther Drug Carrier Syst. 1992;9(2):135-87
references.pmid: 1386002
references.citation: J Cell Biol. 1995 Sep;130(5):1189-96
references.pmid: 7657703
references.citation: Biorheology. 2004;41(6):693-714
references.pmid: 15851845
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6315-20
references.pmid: 16606824
references.citation: Trends Biotechnol. 2008 Aug;26(8):442-9
references.pmid: 18571753
references.citation: J Nanobiotechnology. 2008 Aug 15;6:9
references.pmid: 18702833
references.citation: Nature. 2005 Jul 28;436(7050):568-72
references.pmid: 16049491
references.citation: Am J Pathol. 2007 Sep;171(3):838-45
references.pmid: 17675580
references.citation: Biochim Biophys Acta. 1991 Feb 25;1062(2):142-8
references.pmid: 2004104
references.citation: AAPS J. 2007 May 11;9(2):E128-47
references.pmid: 17614355
references.citation: Microcirculation. 2002 Jul;9(3):177-87
references.pmid: 12080415
references.citation: Nat Nanotechnol. 2008 May;3(5):242-4
references.pmid: 18654511
references.citation: Nat Nanotechnol. 2008 Mar;3(3):131-2
references.pmid: 18654480
references.citation: Int J Pharm. 2010 Jan 4;383(1-2):178-85
references.pmid: 19732814
references.citation: J Clin Oncol. 2005 Nov 1;23(31):7794-803
references.pmid: 16172456
references.citation: Trends Cardiovasc Med. 2008 May;18(4):126-32
references.pmid: 18555185
references.citation: Clin Pharmacol Ther. 2008 May;83(5):761-9
references.pmid: 17957183
references.citation: Nat Nanotechnol. 2008 Mar;3(3):145-50
references.pmid: 18654486
references.citation: Int Immunopharmacol. 2003 Mar;3(3):319-28
references.pmid: 12639809
references.citation: Microsc Res Tech. 2007 Sep;70(9):776-81
references.pmid: 17576122
references.citation: Jpn J Cancer Res. 1994 Apr;85(4):331-4
references.pmid: 7515384
references.citation: Biochem Soc Trans. 1995 Nov;23(4):1073-9
references.pmid: 8654684
references.citation: Science. 1983 Feb 25;219(4587):983-5
references.pmid: 6823562
references.citation: Prog Lipid Res. 2003 Sep;42(5):439-62
references.pmid: 12814645
references.citation: PLoS One. 2008 May 21;3(5):e2242
references.pmid: 18493583
references.citation: Bioorg Med Chem Lett. 2008 Mar 15;18(6):1835-9
references.pmid: 18294846
references.citation: Adv Drug Deliv Rev. 2004 Sep 22;56(11):1649-59
references.pmid: 15350294
references.citation: Biophys J. 1998 Jun;74(6):3264-72
references.pmid: 9635780
references.citation: Microcirculation. 2005 Apr-May;12(3):259-74
references.pmid: 15814435
references.citation: Expert Opin Biol Ther. 2008 Aug;8(8):1063-70
references.pmid: 18613759
references.citation: Circ Res. 1996 Sep;79(3):581-9
references.pmid: 8781491
references.citation: Adv Drug Deliv Rev. 2006 Dec 30;58(15):1622-54
references.pmid: 17123658
references.citation: Anticancer Drugs. 2005 Aug;16(7):691-707
references.pmid: 16027517
references.citation: Curr Opin Chem Biol. 2005 Aug;9(4):343-6
references.pmid: 15967706
references.citation: Ann Biomed Eng. 2004 Jun;32(6):793-802
references.pmid: 15255210
references.citation: Cancer Res. 2006 Oct 15;66(20):10073-82
references.pmid: 17047071
references.citation: Int J Nanomedicine. 2007;2(4):541-50
references.pmid: 18203422
references.citation: J Control Release. 2006 Sep 12;114(3):277-87
references.pmid: 16904220
references.citation: J Control Release. 2001 Jul 6;74(1-3):193-202
references.pmid: 11489495
references.citation: Biomaterials. 2007 Jun;28(18):2915-22
references.pmid: 17363051
references.citation: Cell. 2006 Apr 21;125(2):385-98
references.pmid: 16630824
references.citation: Cancer Res. 2000 Feb 1;60(3):722-7
references.pmid: 10676659
references.citation: Biochem J. 2004 Jan 1;377(Pt 1):159-69
references.pmid: 14505488
references.citation: Biomaterials. 2006 Oct;27(30):5307-14
references.pmid: 16797691
references.citation: J Liposome Res. 2002 Feb-May;12(1-2):5-12
references.pmid: 12604033
references.citation: Invest Ophthalmol Vis Sci. 2006 Nov;47(11):4794-802
references.pmid: 17065490
references.citation: Science. 1989 Dec 8;246(4935):1306-9
references.pmid: 2479986
references.citation: Langmuir. 2007 Mar 27;23(7):4019-25
references.pmid: 17319706
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):4930-4
references.pmid: 16549762
references.citation: Ann Biomed Eng. 2005 Feb;33(2):179-90
references.pmid: 15771271
references.citation: Cancer Res. 1992 Oct 1;52(19):5144-53
references.pmid: 1327501
references.citation: Eur J Pharm Sci. 2005 May;25(1):81-9
references.pmid: 15854804
references.citation: Annu Rev Med. 2008;59:251-65
references.pmid: 17937588
references.citation: Pharmacol Rev. 1999 Dec;51(4):691-743
references.pmid: 10581328
references.citation: Nat Rev Cancer. 2005 Jun;5(6):436-46
references.pmid: 15928674
references.citation: Drug Resist Updat. 2005 Dec;8(6):381-402
references.pmid: 16309948
references.citation: Int J Pharm. 2004 Nov 5;285(1-2):23-34
references.pmid: 15488676
references.citation: Nature. 1998 Apr 30;392(6679 Suppl):5-10
references.pmid: 9579855
references.citation: Br J Cancer. 1996 Dec;74(11):1749-56
references.pmid: 8956788
references.citation: Exp Cell Res. 1998 Jul 10;242(1):265-73
references.pmid: 9665824
references.citation: Ann N Y Acad Sci. 2006 Oct;1082:116-9
references.pmid: 17145932
references.citation: Nat Rev Cancer. 2005 Mar;5(3):161-71
references.pmid: 15738981
references.citation: Cancer Res. 1988 Dec 15;48(24 Pt 1):7022-32
references.pmid: 3191477
references.citation: Angew Chem Int Ed Engl. 2009;48(5):872-97
references.pmid: 19142939
references.citation: Nat Biotechnol. 1997 Jun;15(6):542-6
references.pmid: 9181576
references.citation: Expert Opin Drug Deliv. 2006 May;3(3):311-24
references.pmid: 16640493
references.citation: Biomacromolecules. 2005 Mar-Apr;6(2):914-26
references.pmid: 15762660
references.citation: Bioconjug Chem. 2008 Jul;19(7):1327-38
references.pmid: 18547095
references.citation: Br J Cancer. 2003 Oct 20;89(8):1545-51
references.pmid: 14562030
references.citation: Nat Rev Drug Discov. 2003 May;2(5):347-60
references.pmid: 12750738
references.citation: Biophys J. 2003 Jul;85(1):637-45
references.pmid: 12829517
references.citation: Annu Rev Biomed Eng. 2007;9:257-88
references.pmid: 17439359
references.citation: Nat Rev Drug Discov. 2003 Mar;2(3):214-21
references.pmid: 12612647
references.citation: Cancer Metastasis Rev. 1987;6(4):559-93
references.pmid: 3327633
references.citation: Expert Opin Drug Deliv. 2007 Jul;4(4):359-69
references.pmid: 17683250
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1215-20
references.pmid: 16434473
references.citation: J Cell Sci. 2006 May 1;119(Pt 9):1903-13
references.pmid: 16636075
references.citation: Nat Rev Cancer. 2006 Sep;6(9):688-701
references.pmid: 16900224
references.citation: Cancer Res. 2001 Jun 15;61(12):4750-5
references.pmid: 11406547
references.citation: Int J Nanomedicine. 2007;2(4):689-96
references.pmid: 18203435
references.citation: Radiology. 2002 Sep;224(3):823-9
references.pmid: 12202721
references.citation: Science. 2002 Jun 28;296(5577):2404-7
references.pmid: 12089446
references.citation: Mol Ther. 2003 Jan;7(1):11-8
references.pmid: 12573613
references.citation: Cancer Cell. 2004 Feb;5(2):151-62
references.pmid: 14998491
references.citation: Mol Ther. 2008 Aug;16(8):1450-8
references.pmid: 18560419
references.citation: Biorheology. 2001;38(5-6):415-28
references.pmid: 12016324
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13549-54
references.pmid: 14597719
references.citation: Microvasc Res. 2002 Jul;64(1):21-31
references.pmid: 12074627
references.citation: Nat Rev Drug Discov. 2005 Feb;4(2):145-60
references.pmid: 15688077