Size and Rigidity of Cylindrical Polymer Brushes Dictate Long Circulating Properties <i>In Vivo</i> Markus Müllner Sarah J. Dodds Tri-Hung Nguyen Danielle Senyschyn Christopher J. H. Porter Ben J. Boyd Frank Caruso 10.1021/nn505125f.s001 https://acs.figshare.com/articles/journal_contribution/Size_and_Rigidity_of_Cylindrical_Polymer_Brushes_Dictate_Long_Circulating_Properties_i_In_Vivo_i_/2193325 Studies of spherical nanoengineered drug delivery systems have suggested that particle size and mechanical properties are key determinants of <i>in vivo</i> behavior; however, for more complex structures, detailed analysis of correlations between <i>in vitro</i> characterization and <i>in vivo</i> disposition is lacking. Anisotropic materials in particular bear unknowns in terms of size tolerances for <i>in vivo</i> clearance and the impact of shape and rigidity. Herein, we employed cylindrical polymer brushes (CPBs) to answer questions related to the impact of size, length and rigidity on the <i>in vivo</i> behavior of PEGylated anisotropic structures, in particular their pharmacokinetics and biodistribution. The modular grafting assembly of CPBs allowed for the systematic tailoring of parameters such as aspect ratio or rigidity while keeping the overall chemical composition the same. CPBs with altered length were produced from polyinitiator backbones with different degrees of polymerization. The side chain grafts consisted of a random copolymer of poly[(ethylene glycol) methyl ether methacrylate] (PEGMA) and poly(glycidyl methacrylate) (PGMA), and rendered the CPBs water-soluble. The epoxy groups of PGMA were subsequently reacted with propargylamine to introduce alkyne groups, which in turn were used to attach radiolabels <i>via</i> copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC). Radiolabeling allowed the pharmacokinetics of intravenously injected CPBs to be followed as well as their deposition into major organs post dosing to rats. To alter the rigidity of the CPBs, core–shell-structured CPBs with polycaprolactone (PCL) as a water-insoluble and crystalline core and PEGMA-<i>co</i>-PGMA as the hydrophilic shell were synthesized. This modular buildup of CPBs allowed their shape and rigidity to be altered, which in turn could be used to influence the <i>in vivo</i> circulation behavior of these anisotropic polymer particles. Increasing the aspect ratio or altering the rigidity of the CPBs led to reduced exposure, higher clearance rates, and increased mononuclear phagocytic system (MPS) organ deposition. 2015-02-24 00:00:00 PEGMA rigidity CPB anisotropic polymer particles PCL Cylindrical Polymer Brushes Dictate Long Circulating Properties PGMA side chain grafts PEGylated anisotropic structures MPS organs post dosing nanoengineered drug delivery systems methyl ether methacrylate vivo circulation behavior aspect ratio vivo behavior