title: Influence of Molecular Structure on the In Vivo Performance of Flexible Rod Polyrotaxanes.
abstract: Polyrotaxanes, a family of rod-shaped nanomaterials comprised of noncovalent polymer/macrocycle assemblies, are being used in a growing number of materials and biomedical applications. Their physiochemical properties can vary widely as a function of composition, potentially leading to different in vivo performance outcomes. We sought to characterize the pharmacokinetic profiles, toxicities, and protein corona compositions of 2-hydroxypropyl-β-cyclodextrin polyrotaxanes as a function of variations in macrocycle threading efficiency, molecular weight, and triblock copolymer core structure. We show that polyrotaxane fate in vivo is governed by the structure and dynamics of their rodlike morphologies, such that highly threaded polyrotaxanes are long circulating and deposit in the liver, whereas lung deposition and rapid clearance is observed for species bearing lower 2-hydroxypropyl-β-cyclodextrin threading percentages. Architecture differences also promote recruitment of different serum protein classes and proportions; however, physiochemical differences have little or no influence on their toxicity. These findings provide important structural insights for guiding the development of polyrotaxanes as scaffolds for biomedical applications.
authors.affiliation: Department of Chemistry, Purdue University , Multi-disciplinary Cancer Research Facility, 1203 W. State Street, West Lafayette, Indiana 47907, United States.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Collins
authors.affiliation: Department of Chemistry, Purdue University , Multi-disciplinary Cancer Research Facility, 1203 W. State Street, West Lafayette, Indiana 47907, United States.
authors.forename: Yawo
authors.initials: Y
authors.lastname: Mondjinou
authors.affiliation: Department of Chemistry, Purdue University , Multi-disciplinary Cancer Research Facility, 1203 W. State Street, West Lafayette, Indiana 47907, United States.
authors.forename: Bradley
authors.initials: B
authors.lastname: Loren
authors.affiliation: Purdue University Center for Cancer Research , 201 S. University Street, West Lafayette, Indiana 47907, United States.|Department of Comparative Pathobiology, Purdue University , 625 Harrison Street, West Lafayette, Indiana 47907, United States.
authors.forename: Sandra
authors.initials: S
authors.lastname: Torregrosa-Allen
authors.affiliation: Department of Chemistry, Purdue University , Multi-disciplinary Cancer Research Facility, 1203 W. State Street, West Lafayette, Indiana 47907, United States.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Simmons
authors.affiliation: Purdue University Center for Cancer Research , 201 S. University Street, West Lafayette, Indiana 47907, United States.|Department of Comparative Pathobiology, Purdue University , 625 Harrison Street, West Lafayette, Indiana 47907, United States.
authors.forename: Bennett D
authors.initials: BD
authors.lastname: Elzey
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
authors.forename: Nadia
authors.initials: N
authors.lastname: Ayat
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University , 10900 Euclid Avenue, Cleveland, Ohio 44106, United States.
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Lu
authors.affiliation: Department of Chemistry, Purdue University , Multi-disciplinary Cancer Research Facility, 1203 W. State Street, West Lafayette, Indiana 47907, United States.|Purdue University Center for Cancer Research , 201 S. University Street, West Lafayette, Indiana 47907, United States.|Weldon School of Biomedical Engineering, Purdue University , 206 S. Martin Jischke Drive, West Lafayette, Indiana 47907, United States.
authors.forename: David
authors.initials: D
authors.lastname: Thompson
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D003505:Cyclodextrins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D020442:Poloxamer / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D011092:Polyethylene Glycols; D011108:Polymers / Q000737:chemistry*; D043862:Rotaxanes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D001672:Biocompatible Materials; D003505:Cyclodextrins; D011108:Polymers; D043862:Rotaxanes; C475673:polyrotaxane; D020442:Poloxamer; D011092:Polyethylene Glycols