title: Mechanisms of cooperation in cancer nanomedicine: towards systems nanotechnology.
abstract: Nanoparticles are designed to deliver therapeutics and diagnostics selectively to tumors. Their size, shape, charge, material, coating, and cargo determine their individual functionalities. A systems approach could help predict the behavior of trillions of nanoparticles interacting in complex tumor environments. Engineering these nanosystems may lead to biomimetic strategies where interactions between nanoparticles and their environment give rise to cooperative behaviors typically seen in natural self-organized systems. Examples include nanoparticles that communicate the location of a tumor to amplify tumor homing or self-assemble and disassemble to optimize nanoparticle transport. The challenge is to discover which nanoparticle designs lead to a desired system behavior. To this end, novel nanomaterials, deep understanding of biology, and computational tools are emerging as the next frontier.
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Engineering Mathematics, University of Bristol, Bristol BS8 1TR, UK.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hauert
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: sbhatia@mit.edu.
authors.forename: Sangeeta N
authors.initials: SN
authors.lastname: Bhatia
mesh_terms: D035843:Biomedical Research / Q000639:trends; D006801:Humans; D050997:Nanomedicine / Q000379:methods* / Q000639:trends; D036103:Nanotechnology / Q000379:methods* / Q000639:trends; D009369:Neoplasms / Q000175:diagnosis* / Q000628:therapy*
keywords: cancer; cooperation; nanoparticles; swarming; systems nanotechnology
references.citation: Trends Biotechnol. 2009 Jun;27(6):350-8
references.pmid: 19409634
references.citation: Annu Rev Med. 2012;63:185-98
references.pmid: 21888516
references.citation: Nanomedicine (Lond). 2008 Oct;3(5):703-17
references.pmid: 18817471
references.citation: Crit Rev Biomed Eng. 2012;40(1):21-41
references.pmid: 22428797
references.citation: Angew Chem Int Ed Engl. 2013 Jun 24;52(26):6580-9
references.pmid: 23670869
references.citation: Acc Chem Res. 2011 Oct 18;44(10):1009-17
references.pmid: 21761902
references.citation: Adv Mater. 2013 Jul 12;25(26):3508-25
references.pmid: 23703805
references.citation: Adv Mater. 2012 Jul 24;24(28):3779-802
references.pmid: 22610698
references.citation: Curr Opin Biotechnol. 2013 Aug;24(4):682-9
references.pmid: 23726153
references.citation: Colloids Surf B Biointerfaces. 2010 Jan 1;75(1):1-18
references.pmid: 19782542
references.citation: Adv Drug Deliv Rev. 2012 Oct;64(13):1447-58
references.pmid: 22772034
references.citation: Pharm Res. 2008 Jan;25(1):55-71
references.pmid: 17551809
references.citation: Angiogenesis. 2010 Jun;13(2):113-30
references.pmid: 20623252
references.citation: Biomaterials. 2011 Sep;32(26):6226-33
references.pmid: 21658757
references.citation: J Am Chem Soc. 2007 May 16;129(19):6064-5
references.pmid: 17447766
references.citation: Trends Biotechnol. 2006 Feb;24(2):62-7
references.pmid: 16380179
references.citation: Adv Mater. 2012 Jul 24;24(28):3803-22, 3710
references.pmid: 22674563
references.citation: Adv Mater. 2012 Jul 24;24(28):3724-46
references.pmid: 22641380
references.citation: Science. 2014 Apr 4;344(6179):65-9
references.pmid: 24625926
references.citation: J Control Release. 2013 Jun 10;168(2):179-99
references.pmid: 23524187
references.citation: Adv Mater. 2012 Jul 24;24(28):3747-56
references.pmid: 22550056
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11194-9
references.pmid: 20534561
references.citation: ACS Nano. 2012 Oct 23;6(10):8620-31
references.pmid: 22909216
references.citation: Nature. 2005 Jul 28;436(7050):568-72
references.pmid: 16049491
references.citation: Adv Drug Deliv Rev. 2011 Jan-Feb;63(1-2):119-28
references.pmid: 20933026
references.citation: Annu Rev Biomed Eng. 2013;15:253-82
references.pmid: 23642243
references.citation: ACS Nano. 2013 Apr 23;7(4):3388-402
references.pmid: 23530622
references.citation: Nat Rev Drug Discov. 2008 Sep;7(9):771-82
references.pmid: 18758474
references.citation: Bioessays. 2009 Feb;31(2):190-7
references.pmid: 19204991
references.citation: Adv Drug Deliv Rev. 2008 Aug 17;60(11):1266-1277
references.pmid: 18508154
references.citation: PLoS One. 2011;6(9):e24696
references.pmid: 21935441
references.citation: Trends Biotechnol. 2010 Apr;28(4):181-8
references.pmid: 20079548
references.citation: Acc Chem Res. 2011 Oct 18;44(10):947-56
references.pmid: 21848277
references.citation: Biochim Biophys Acta. 2011 Mar;1810(3):317-29
references.pmid: 20493927
references.citation: Integr Biol (Camb). 2013 Jan;5(1):96-107
references.pmid: 22869005
references.citation: Nano Today. 2013 Dec 1;8(6):566-576
references.pmid: 25009578
references.citation: Trends Cogn Sci. 2009 Jan;13(1):36-43
references.pmid: 19058992
references.citation: J Control Release. 2010 Dec 1;148(2):135-46
references.pmid: 20797419
references.citation: Adv Drug Deliv Rev. 2004 Sep 22;56(11):1649-59
references.pmid: 15350294
references.citation: Science. 2012 Nov 16;338(6109):903-10
references.pmid: 23161990
references.citation: Int J Pharm. 2006 Jan 3;307(1):93-102
references.pmid: 16303268
references.citation: Adv Drug Deliv Rev. 2011 Nov;63(14-15):1228-46
references.pmid: 21777633
references.citation: ACS Nano. 2013 Dec 23;7(12):10671-80
references.pmid: 24215426
references.citation: Adv Genet. 2010;69:31-64
references.pmid: 20807601
references.citation: Nature. 2008 Apr 3;452(7187):580-9
references.pmid: 18385732
references.citation: Adv Mater. 2010 Feb 23;22(8):880-5
references.pmid: 20217810
references.citation: Acc Chem Res. 2011 Oct 18;44(10):979-89
references.pmid: 21902173
references.citation: Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4311-6
references.pmid: 20160077
references.citation: Nat Nanotechnol. 2010 Jan;5(1):61-6
references.pmid: 19898497
references.citation: Science. 2013 Feb 22;339(6122):971-5
references.pmid: 23430657
references.citation: ACS Nano. 2011 Jun 28;5(6):4284-92
references.pmid: 21513353
references.citation: Nat Biotechnol. 2013 Jan;31(1):63-70
references.pmid: 23242163
references.citation: Nat Rev Drug Discov. 2010 Aug;9(8):615-27
references.pmid: 20616808
references.citation: Methods Enzymol. 2012;503:255-68
references.pmid: 22230572
references.citation: Science. 2012 Feb 17;335(6070):831-4
references.pmid: 22344439
references.citation: Ther Deliv. 2012 Apr;3(4):457-78
references.pmid: 22834077
references.citation: Nat Commun. 2013;4:2718
references.pmid: 24177351
references.citation: J Control Release. 2012 Dec 10;164(2):115-24
references.pmid: 22484196
references.citation: Int J Nanomedicine. 2007;2(2):265-74
references.pmid: 17722554
references.citation: Nano Lett. 2009 May;9(5):1909-15
references.pmid: 19344179
references.citation: J Am Chem Soc. 2009 Sep 30;131(38):13639-45
references.pmid: 19772360
references.citation: Nat Mater. 2012 Sep;11(9):768-74
references.pmid: 22751181
references.citation: Lab Chip. 2008 Sep;8(9):1468-77
references.pmid: 18818801
references.citation: Trends Ecol Evol. 2010 Jan;25(1):28-34
references.pmid: 19735961
references.citation: Science. 2014 Feb 14;343(6172):754-8
references.pmid: 24531967
references.citation: Acc Chem Res. 2008 Jun;41(6):749-59
references.pmid: 18507402
references.citation: Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):981-6
references.pmid: 20080556
references.citation: ACS Nano. 2013 Oct 22;7(10):9001-9
references.pmid: 24015809
references.citation: J Control Release. 2012 Dec 28;164(3):265-75
references.pmid: 22800576
references.citation: Cancer Res. 2009 May 1;69(9):3892-900
references.pmid: 19366797
references.citation: ACS Nano. 2013 Sep 24;7(9):8089-97
references.pmid: 23961973
references.citation: Expert Opin Drug Deliv. 2012 Dec;9(12):1525-38
references.pmid: 23121385
references.citation: MAbs. 2011 Sep-Oct;3(5):467-78
references.pmid: 21814040
references.citation: Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):125-48
references.pmid: 11259837
references.citation: Nat Rev Clin Oncol. 2010 Nov;7(11):653-64
references.pmid: 20838415
references.citation: Small. 2011 Jul 18;7(14):1919-31
references.pmid: 21695781
references.citation: Nat Mater. 2013 Nov;12(11):967-77
references.pmid: 24150415
references.citation: Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):10963-8
references.pmid: 21690358
references.citation: Chem Soc Rev. 2012 Apr 7;41(7):2971-3010
references.pmid: 22388185
references.citation: Nature. 2010 Aug 5;466(7307):756-60
references.pmid: 20686574
references.citation: J Cell Biol. 2010 Mar 22;188(6):759-68
references.pmid: 20231381
references.citation: Angiogenesis. 2013 Jul;16(3):481-92
references.pmid: 23389639
references.citation: Nat Rev Cancer. 2010 Nov;10(11):785-94
references.pmid: 20944664
references.citation: Adv Mater. 2011 Sep 22;23(36):H217-47
references.pmid: 21842473
references.citation: Clin Cancer Res. 2008 Mar 1;14(5):1310-6
references.pmid: 18316549
references.citation: Nature. 2009 May 21;459(7245):414-8
references.pmid: 19458720
references.citation: Adv Drug Deliv Rev. 2013 Jan;65(1):71-9
references.pmid: 23088862
references.citation: ACS Nano. 2013 Oct 22;7(10):8605-15
references.pmid: 24053333
references.citation: Nat Biotechnol. 2007 Oct;25(10):1165-70
references.pmid: 17891134
references.citation: Adv Drug Deliv Rev. 2011 Nov;63(14-15):1361-70
references.pmid: 22016112
references.citation: Adv Drug Deliv Rev. 2014 Dec 15;79-80:107-18
references.pmid: 24819216
references.citation: Nat Mater. 2011 Jun 19;10(7):545-52
references.pmid: 21685903
references.citation: Trends Biotechnol. 2011 Jul;29(7):323-32
references.pmid: 21489647
references.citation: Proc Natl Acad Sci U S A. 2011 Feb 8;108(6):2426-31
references.pmid: 21245339
references.citation: Adv Drug Deliv Rev. 2009 Nov 12;61(13):1203-13
references.pmid: 19699247
references.citation: Small. 2008 Sep;4(9):1307-12
references.pmid: 18690639
references.citation: J Control Release. 2012 Jul 20;161(2):399-402
references.pmid: 22100439
references.citation: Adv Drug Deliv Rev. 2008 Aug 17;60(11):1241-1251
references.pmid: 18508157