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Accelerated Blood Clearance Phenomenon Reduces the Passive Targeting of PEGylated Nanoparticles in Peripheral Arterial Disease.
Im, Hyung-Jun; England, Christopher G; Feng, Liangzhu; Graves, Stephen A; Hernandez, Reinier; Nickles, Robert J; Liu, Zhuang; Lee, Dong Soo; Cho, Steve Y; Cai, Weibo.
Afiliação
  • Im HJ; Department of Radiology, University of Wisconsin-Madison , Madison, Wisconsin 53705, United States.
  • England CG; Department of Molecular Medicine and Biopharmaceutical Sciences, Department of Nuclear Medicine, Seoul National University , Seoul 110-744, Korea.
  • Feng L; Department of Medical Physics, University of Wisconsin-Madison , Madison, Wisconsin 53705, United States.
  • Graves SA; Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices Laboratory, Soochow University Suzhou , Jiangsu 215123, China.
  • Hernandez R; Department of Medical Physics, University of Wisconsin-Madison , Madison, Wisconsin 53705, United States.
  • Nickles RJ; Department of Medical Physics, University of Wisconsin-Madison , Madison, Wisconsin 53705, United States.
  • Liu Z; Department of Medical Physics, University of Wisconsin-Madison , Madison, Wisconsin 53705, United States.
  • Lee DS; Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices Laboratory, Soochow University Suzhou , Jiangsu 215123, China.
  • Cho SY; Department of Molecular Medicine and Biopharmaceutical Sciences, Department of Nuclear Medicine, Seoul National University , Seoul 110-744, Korea.
  • Cai W; Department of Radiology, University of Wisconsin-Madison , Madison, Wisconsin 53705, United States.
ACS Appl Mater Interfaces ; 8(28): 17955-63, 2016 Jul 20.
Article em En | MEDLINE | ID: mdl-27340833
ABSTRACT
Peripheral arterial disease (PAD) is a leading global health concern. Due to limited imaging and therapeutic options, PAD and other ischemia-related diseases may benefit from the use of long circulating nanoparticles as imaging probes and/or drug delivery vehicles. Polyethylene glycol (PEG)-conjugated nanoparticles have shown shortened circulation half-lives in vivo when injected multiple times into a single subject. This phenomenon has become known as the accelerated blood clearance (ABC) effect. The phenomenon is of concern for clinical translation of nanomaterials as it limits the passive accumulation of nanoparticles in many diseases, yet it has not been evaluated using inorganic or organic-inorganic hybrid nanoparticles. Herein, we found that the ABC phenomenon was induced by reinjection of PEGylated long circulating organic-inorganic hybrid nanoparticles, which significantly reduced the passive targeting of (64)Cu-labeled PEGylated reduced graphene oxide-iron oxide nanoparticles ((64)Cu-RGO-IONP-PEG) in a murine model of PAD. Positron emission tomography (PET) imaging was performed at 3, 10, and 17 days postsurgical induction of hindlimb ischemia. At day 3 postsurgery, the nanoparticles displayed a long circulation half-life with enhanced accumulation in the ischemic hindlimb. At days 10 and 17 postsurgery, reinjected mice displayed a short circulation half-life and lower accumulation of the nanoparticles in the ischemic hindlimb, in comparison to the naïve group. Also, reinjected mice showed significantly higher liver uptake than the naïve group, indicating that the nanoparticles experienced higher sequestration by the liver in the reinjected group. Furthermore, photoacoustic (PA) imaging and Prussian blue staining confirmed the enhanced accumulation of the nanoparticles in the liver tissue of reinjected mice. These findings validate the ABC phenomenon using long circulating organic-inorganic hybrid nanoparticles upon multiple administrations to the same animal, which may provide valuable insight into the future clinical applications of nanoparticles for imaging and treatment of PAD.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 Base de dados: MEDLINE Assunto principal: Polietilenoglicóis / Nanopartículas / Doença Arterial Periférica Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: ACS Appl Mater Interfaces Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 2_ODS3 Base de dados: MEDLINE Assunto principal: Polietilenoglicóis / Nanopartículas / Doença Arterial Periférica Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: ACS Appl Mater Interfaces Ano de publicação: 2016 Tipo de documento: Article