Structural effects on the biodistribution and positron emission tomography (PET) imaging of well-defined (64)Cu-labeled nanoparticles comprised of amphiphilic block graft copolymers.
The synthesis of poly(methyl methacrylate-co-methacryloxysuccinimide-graft-poly(ethylene glycol)) (PMMA-co-PMASI-g-PEG) via living free radical polymerization provides a convenient route to well-defined amphiphilic graft copolymers having a controllable number of reactive functional groups, variable length PEG grafts, and low polydispersity. These copolymers were shown to form PMMA-core/PEG-shell nanoparticles upon hydrophobic collapse in water, with the hydrodynamic size being defined by the molecular weight of the backbone and the PEG grafts. Functionalization of these polymeric nanoparticles with a 1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) ligand capable of chelating radioactive 64Cu nuclei enabled the biodistribution and in vivo positron emission tomography of these materials to be studied and directly correlated to the initial structure. Results indicate that nanoparticles with increasing PEG chain lengths show increased blood circulation and low accumulation in excretory organs, suggesting the possible use of these materials as stealth carriers for medical imaging and systemic administration.
Pressly
Eric D
ED
Materials Research Laboratory, Department of Chemistry, University of California, Santa Barbara, CA 93106, USA.
Rossin
Raffaella
R
Hagooly
Aviv
A
Fukukawa
Ken-Ichi
K
Messmore
Benjamin W
BW
Welch
Michael J
MJ
Wooley
Karen L
KL
Lamm
Matthew S
MS
Hule
Rohan A
RA
Pochan
Darrin J
DJ
Hawker
Craig J
CJ
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D003301:Copper Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D020285:Cryoelectron Microscopy; D005260:Female; D005609:Free Radicals; D008024:Ligands; D008689:Methacrylates / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D019904:Polymethyl Methacrylate / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000295:instrumentation* / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001672:Biocompatible Materials; D003301:Copper Radioisotopes; D005609:Free Radicals; D008024:Ligands; D008689:Methacrylates; C421283:poly(ethylene glycol)-dimethacrylate; D011092:Polyethylene Glycols; D003300:Copper; D019904:Polymethyl Methacrylate