Abstract
Selective targeting of constructs to pathological cells by conjugating one or more ligands for an overexpressed receptor has been proposed to enhance the delivery of therapeutics to and imaging of specific cells of interest. Previous work in our lab has demonstrated the efficacy of targeting glioblastoma cells with a multivalent, biomacromolecular construct targeted to the alpha(6)beta(1)-integrin. However, solid-phase synthesis of this construct was inefficient in terms of cost and number of steps. Here we show proof-of-concept of a two-step synthesis that can be used to create similar constructs targeted to glioblastoma cells. Specifically, a well-defined aldehyde side chain polymer was synthesized and oxime chemistry was employed to conjugate ligands specific for the alpha(6)beta(1)-integrin. These constructs were then tested in competitive binding, fluorescence binding, and toxicity assays, through which we demonstrate that constructs are multivalent, preferentially target glioblastoma cells, and are nontoxic. Rapid, potentially low-cost synthesis of targeting constructs will enable their use in the clinic and for personalized medicine.
References
Mar 15, 1994·Proceedings of the National Academy of Sciences of the United States of America·R H BoboE H Oldfield
Nov 1, 1996·The Journal of Biological Chemistry·H NakaharaW T Chen
Nov 26, 1998·The Journal of Biological Chemistry·M NomizuY Yamada
May 29, 2003·Chemistry : a European Journal·Georgette ThumshirnHorst Kessler
Dec 20, 2003·Bioorganic & Medicinal Chemistry Letters·Josef VagnerVictor J Hruby
Jan 28, 2004·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Mohsen Shadidi, Mouldy Sioud
Jun 19, 2004·Analytical Biochemistry·Heather L HandlRobert J Gillies
Dec 9, 2004·Expert Opinion on Therapeutic Targets·Heather L HandlRobert J Gillies
Feb 1, 2005·Science·X MichaletS Weiss
Jul 12, 2005·Annual Review of Biomedical Engineering·A Paul AlivisatosCarolyn Larabell
Jul 26, 2005·Biochemical and Biophysical Research Communications·Emmanuel ChangJennifer L West
Sep 1, 2005·Annals of Biomedical Engineering·Michael R Caplan, Elena V Rosca
Apr 14, 2006·Expert Opinion on Biological Therapy·William R ShapiroJoseph S Shan
May 17, 2006·Technology in Cancer Research & Treatment·Mitomu KioiRaj K Puri
Dec 19, 2006·Molecular Cancer Therapeutics·A B MadhankumarJames R Connor
Jan 30, 2007·Molecular Cancer Research : MCR·Seung-Min LeeByung-Heon Lee
Jun 30, 2007·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jungyeon HwangHeather D Maynard
Sep 7, 2007·Journal of Neuro-oncology·Ronald J BernardiJennifer L West
Nov 17, 2007·Cancer Research·Tong-Young LeeHan-Chung Wu
Nov 28, 2007·Biomacromolecules·Elena V RoscaMichael R Caplan
Apr 12, 2008·Neuro-oncology·John H SampsonDarell D Bigner
Apr 22, 2008·Annals of Biomedical Engineering·Jill M StukelMichael R Caplan
Dec 10, 2008·Drug Discovery Today·Lois A Lampson
Dec 18, 2008·Small·Lily YangShuming Nie
Jul 4, 2009·Biotechnology and Bioengineering·Elena V RoscaMichael R Caplan
Nov 2, 1998·Angewandte Chemie·Mathai MammenGeorge M Whitesides
Citations
Nov 24, 2011·Biomacromolecules·Vijayakameswara Rao NRaja Shunmugam
Jan 14, 2011·Chemical Communications : Chem Comm·Rebecca M BroyerHeather D Maynard
Oct 11, 2011·Therapeutic Delivery·Chuda ChittasuphoCory Berkland
Nov 11, 2014·Tetrahedron Letters·Katherine D McReynoldsHoang Le
Jul 24, 2010·Journal of Oncology·Jessie ZhongGeraldine M O'Neill
Oct 15, 2013·Drug Delivery·Bin HuChang-Lie Fan
Mar 12, 2011·Colloids and Surfaces. B, Biointerfaces·Bin HuYa-Jun Duan
Jul 14, 2011·Angewandte Chemie·Boris ObermeierHolger Frey
Dec 5, 2013·Chemistry : a European Journal·Sébastien UlrichPascal Dumy
Dec 2, 2010·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Eleni MarkoutsaSophia G Antimisiaris
Jan 1, 2013·Macromolecules·Jingquan LiuHeather D Maynard
Nov 5, 2016·Nanomedicine : Nanotechnology, Biology, and Medicine·Maria GregoriDavid Allsop
Apr 21, 2017·Nanoscale·Gabriele RucinskaiteRoberto de la Rica
Feb 23, 2021·Angewandte Chemie·Emma E BrothertonSteven P Armes
Feb 1, 2011·ACS Nano·Monica ShokeenCarolyn J Anderson
Mar 8, 2011·ACS Nano·Chuda ChittasuphoCory Berkland
Jul 31, 2016·ACS Omega·Sayantani BhattacharyaRaja Shunmugam