Document Detail


Nanoparticulate assemblies of amphiphiles and diagnostically active materials for multimodality imaging.
MedLine Citation:
PMID:  19435319     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Modern medicine has greatly benefited from recent dramatic improvements in imaging techniques. The observation of physiological events through interactions manipulated at the molecular level offers unique insight into the function (and dysfunction) of the living organism. The tremendous advances in the development of nanoparticulate molecular imaging agents over the past decade have made it possible to noninvasively image the specificity, pharmacokinetic profiles, biodistribution, and therapeutic efficacy of many novel compounds. Several types of nanoparticles have demonstrated utility for biomedical purposes, including inorganic nanocrystals, such as iron oxide, gold, and quantum dots. Moreover, natural nanoparticles, such as viruses, lipoproteins, or apoferritin, as well as hybrid nanostructures composed of inorganic and natural nanoparticles, have been applied broadly. However, among the most investigated nanoparticle platforms for biomedical purposes are lipidic aggregates, such as liposomal nanoparticles, micelles, and microemulsions. Their relative ease of preparation and functionalization, as well as the ready synthetic ability to combine multiple amphiphilic moieties, are the most important reasons for their popularity. Lipid-based nanoparticle platforms allow the inclusion of a variety of imaging agents, ranging from fluorescent molecules to chelated metals and nanocrystals. In recent years, we have created a variety of multifunctional lipid-based nanoparticles for molecular imaging; many are capable of being used with more than one imaging technique (that is, with multimodal imaging ability). These nanoparticles differ in size, morphology, and specificity for biological markers. In this Account, we discuss the development and characterization of five different particles: liposomes, micelles, nanocrystal micelles, lipid-coated silica, and nanocrystal high-density lipoprotein (HDL). We also demonstrate their application for multimodal molecular imaging, with the main focus on magnetic resonance imaging (MRI), optical techniques, and transmission electron microscopy (TEM). The functionalization of the nanoparticles and the modulation of their pharmacokinetics are discussed. Their application for molecular imaging of key processes in cancer and cardiovascular disease are shown. Finally, we discuss a recent development in which the endogenous nanoparticle HDL was modified to carry different diagnostically active nanocrystal cores to enable multimodal imaging of macrophages in experimental atherosclerosis. The multimodal characteristics of the different contrast agent platforms have proven to be extremely valuable for validation purposes and for understanding mechanisms of particle-target interaction at different levels, ranging from the entire organism down to cellular organelles.
Authors:
Willem J M Mulder; Gustav J Strijkers; Geralda A F van Tilborg; David P Cormode; Zahi A Fayad; Klaas Nicolay
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Accounts of chemical research     Volume:  42     ISSN:  1520-4898     ISO Abbreviation:  Acc. Chem. Res.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-07-21     Completed Date:  2009-10-13     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  0157313     Medline TA:  Acc Chem Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  904-14     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiovascular Diseases / pathology
Cholesterol, HDL / chemistry,  metabolism
Diagnostic Imaging*
Fluorescent Dyes / chemistry
Gold / chemistry
Lipids / chemistry*
Liposomes / chemistry,  pharmacokinetics,  pharmacology
Magnetic Resonance Imaging
Magnetics
Mice
Micelles
Microscopy, Electron, Transmission
Nanoparticles / chemistry,  diagnostic use*
Neoplasms / pathology
Quantum Dots
Silicon Dioxide / chemistry
Surface-Active Agents / chemistry
Grant Support
ID/Acronym/Agency:
R01 EB009638/EB/NIBIB NIH HHS; R01 EB009638-06/EB/NIBIB NIH HHS; R01 HL071021/HL/NHLBI NIH HHS; R01 HL071021-07/HL/NHLBI NIH HHS; R01 HL078667/HL/NHLBI NIH HHS; R01 HL078667-04S1/HL/NHLBI NIH HHS; R01 HL71021/HL/NHLBI NIH HHS; R01 HL78667/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cholesterol, HDL; 0/Fluorescent Dyes; 0/Lipids; 0/Liposomes; 0/Micelles; 0/Surface-Active Agents; 7440-57-5/Gold; 7631-86-9/Silicon Dioxide
Comments/Corrections

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