title: Evaluation of multivalent, functional polymeric nanoparticles for imaging applications.
abstract: A series of multivalent, functional polymer nanoparticles with diagnostic/imaging units and targeting ligands for molecular targeting were synthesized with the loading of the chain-end-functionalized GRGDS peptide targeting sequence (model system based on integrin α(v)β(3)) ranging from 0 to 50%. Accurate structural and functional group control in these systems was achieved through a modular approach involving the use of multiple functionalized macromonomer/monomer units combined with living free radical polymerization. In cellulo results show an increase in uptake in α(v)β(3) integrin-positive U87MG glioblastoma cells with increasing RGD loading and a possible upper limit on the effectiveness of the number of RGD peptides for targeting α(v)β(3) integrin. Significantly, this increased targeting efficiency is coupled with in vivo biodistribution results, which show decreased blood circulation and increased liver uptake with increasing RGD loading. The results demonstrate the importance of controlling ligand loading in order to achieve optimal performance for therapeutic and imaging applications for multivalent nanoparticle-based systems.
authors.affiliation: Mallinckrodt Institute of Radiology, Washington University, St. Louis, Missouri 63110, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Shokeen
authors.forename: Eric D
authors.initials: ED
authors.lastname: Pressly
authors.forename: Aviv
authors.initials: A
authors.lastname: Hagooly
authors.forename: Alexander
authors.initials: A
authors.lastname: Zheleznyak
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ramos
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Fiamengo
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Welch
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Hawker
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Anderson
mesh_terms: D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity
chemical_list: D039302:Integrin alphaVbeta3; D011108:Polymers