title: Targeting of tumor-associated macrophages made possible by PEG-sheddable, mannose-modified nanoparticles.
abstract: It is increasingly evident that tumor-associated macrophages (TAMs) play an important role in tumor invasion, proliferation, and metastasis. While delivery of drugs, imaging agents, and vaccines to TAMs was achieved by exploiting membrane receptors on TAMs, the uptake by normal macrophages remains an issue. In this communication, we report a PEG-sheddable, mannose-modified nanoparticle platform that can efficiently target TAMs via mannose-mannose receptor recognition after acid-sensitive PEG shedding in the acidic tumor microenvironment, while their uptake by normal macrophages in the mononuclear phagocyte system (MPS) organs was significantly reduced due to effective PEG shielding at neutral pH. These nanoparticles have the potential to target drugs of interest to TAMs, with decreased uptake by normal macrophages.
authors.affiliation: Pharmaceutics Division, College of Pharmacy, The University of Texas at Austin , Austin, Texas 78712, United States.
authors.forename: Saijie
authors.initials: S
authors.lastname: Zhu
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Niu
authors.forename: Hannah
authors.initials: H
authors.lastname: O'Mary
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Cui
mesh_terms: D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008358:Mannose / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D011092:Polyethylene Glycols; D008358:Mannose
references.citation: J Pharmacol Exp Ther. 2002 Mar;300(3):976-83
references.pmid: 11861806
references.citation: Small. 2008 Nov;4(11):2043-50
references.pmid: 18949788
references.citation: J Clin Invest. 2006 Aug;116(8):2132-2141
references.pmid: 16862213
references.citation: Semin Respir Crit Care Med. 2004 Feb;25(1):21-31
references.pmid: 16088446
references.citation: Nanomedicine. 2012 May;8(4):468-77
references.pmid: 21782778
references.citation: Cell Tissue Res. 1990 May;260(2):215-22
references.pmid: 2141546
references.citation: Nanomedicine. 2011 Dec;7(6):730-43
references.pmid: 21658473
references.citation: Cancer Res. 2009 Dec 15;69(24):9395-403
references.pmid: 19951991
references.citation: Nat Rev Cancer. 2004 Jan;4(1):71-8
references.pmid: 14708027
references.citation: Small. 2008 Oct;4(10):1640-5
references.pmid: 18819168
references.citation: Int J Hyperthermia. 1995 Mar-Apr;11(2):211-6
references.pmid: 7790735
references.citation: Pharm Res. 2008 Jan;25(1):55-71
references.pmid: 17551809
references.citation: Small. 2012 Aug 20;8(16):2585-94
references.pmid: 22674655
references.citation: Biomaterials. 2013 Mar;34(9):2327-39
references.pmid: 23261218
references.citation: Small. 2012 Sep 24;8(18):2819-22
references.pmid: 22777707
references.citation: Cell. 2010 Apr 2;141(1):39-51
references.pmid: 20371344
references.citation: Bioconjug Chem. 2012 May 16;23(5):966-80
references.pmid: 22471294
references.citation: Endocr Relat Cancer. 2008 Dec;15(4):1069-74
references.pmid: 18719091
references.citation: Cancer Immunol Immunother. 2009 Oct;58(10):1577-86
references.pmid: 19238383
references.citation: Cancer Res. 2005 Apr 1;65(7):2964-71
references.pmid: 15805300
references.citation: Arthritis Rheum. 2005 Sep;52(9):2666-75
references.pmid: 16142741
references.citation: Biochim Biophys Acta. 2009 Aug;1796(1):11-8
references.pmid: 19269310
references.citation: Cell. 2006 Jan 27;124(2):263-6
references.pmid: 16439202
references.citation: Bioconjug Chem. 2006 Jul-Aug;17(4):943-9
references.pmid: 16848401
references.citation: J Pathol. 2002 Mar;196(3):254-65
references.pmid: 11857487
references.citation: Int J Pharm. 2006 Jan 3;307(1):93-102
references.pmid: 16303268
references.citation: J Phys Condens Matter. 2010 Jul 21;22(28):285102
references.pmid: 21399291
references.citation: Cancer Res. 2012 Aug 15;72(16):4165-77
references.pmid: 22719068
references.citation: Vasc Cell. 2013 Mar 21;5(1):5
references.pmid: 23514200
references.citation: J Hepatol. 2005 Jan;42(1):102-9
references.pmid: 15629514
references.citation: Pharm Res. 2009 Dec;26(12):2588-98
references.pmid: 19842021
references.citation: J Pharm Sci. 1995 Apr;84(4):493-8
references.pmid: 7629743
references.citation: Trends Immunol. 2002 Nov;23(11):549-55
references.pmid: 12401408
references.citation: J Control Release. 2011 Apr 10;151(1):10-7
references.pmid: 21130819
references.citation: Biomaterials. 2010 Feb;31(6):1360-71
references.pmid: 19883938
references.citation: J Control Release. 2012 Mar 10;158(2):286-92
references.pmid: 22119956
references.citation: Biomaterials. 2010 Feb;31(6):1085-92
references.pmid: 19880176
references.citation: Gene Ther. 2000 Feb;7(4):292-9
references.pmid: 10694809
references.citation: Biomaterials. 2004 Jun;25(14):2843-9
references.pmid: 14962562
references.citation: Autoimmun Rev. 2012 Jul;11(9):621-6
references.pmid: 22094710
references.citation: Biomaterials. 2010 Oct;31(30):7813-26
references.pmid: 20656348
references.citation: Int J Pharm. 2011 May 16;409(1-2):278-88
references.pmid: 21371545
references.citation: Annu Rev Immunol. 2005;23:901-44
references.pmid: 15771589
references.citation: Br J Cancer. 2006 Aug 7;95(3):272-81
references.pmid: 16832418
references.citation: J Drug Deliv. 2011;2011:727241
references.pmid: 21512579
references.citation: Mol Ther. 2005 Mar;11(3):418-25
references.pmid: 15727938
references.citation: Pharm Res. 2010 Aug;27(8):1584-96
references.pmid: 20422265
references.citation: Semin Cancer Biol. 2012 Aug;22(4):289-97
references.pmid: 22349514
references.citation: Biomaterials. 2012 Nov;33(31):7785-93
references.pmid: 22840225
references.citation: Nat Mater. 2009 Jun;8(6):526-33
references.pmid: 19404239
references.citation: Ann Surg Oncol. 2012 Jul;19(7):2264-71
references.pmid: 22350599