Blood clearance and biodistribution of polymer brush-afforded silica particles prepared by surface-initiated living radical polymerization.
The physiological properties of polymer brush-afforded silica particles prepared by surface-initiated living radical polymerization were investigated in terms of the circulation lifetime in the blood and distribution in tissues. Hydrophilic polymers consisting mainly of poly(poly(ethylene glycol) methyl ether methacrylate) were grafted onto silica particles by surface-initiated atom transfer radical polymerization that was mediated by a copper complex to produce hairy hybrid particles. A series of hybrid particles was synthesized by varying the diameter of the silica core and the chain length of the polymer brush to examine the relationship between their physicochemical and physiological properties. The hybrid particles were injected intravenously into mice to investigate systematically their blood clearance and body distribution. It was revealed that the structural features of the hybrid particles significantly affected their in vivo pharmacokinetics. Some hybrid particles exhibited an excellently prolonged circulation lifetime in the blood with a half life of ∼20 h. When such hybrid particles were injected intravenously into a tumor-bearing mouse, they preferentially accumulated in tumor tissue. The tumor-targeted delivery was optically visualized using hybrid particles grafted with fluorescence-labeled polymer brushes.
Institute for Chemical Research, Kyoto University , Uji, Kyoto 611-0011, Japan. ohno@scl.kyoto-u.ac.jp
Kohji
K
Ohno
Tatsuki
T
Akashi
Yoshinobu
Y
Tsujii
Masaya
M
Yamamoto
Yasuhiko
Y
Tabata
D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology*; D005260:Female; D005609:Free Radicals / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008689:Methacrylates / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D058105:Polymerization; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics*; D012822:Silicon Dioxide / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D013499:Surface Properties; D013696:Temperature; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D005609:Free Radicals; D008689:Methacrylates; D011108:Polymers; C524499:polyethylene glycol methacrylate; D011092:Polyethylene Glycols; D012822:Silicon Dioxide