Skip to Content
Merck
  • Dextran-coated iron oxide nanoparticles: a versatile platform for targeted molecular imaging, molecular diagnostics, and therapy.

Dextran-coated iron oxide nanoparticles: a versatile platform for targeted molecular imaging, molecular diagnostics, and therapy.

Accounts of chemical research (2011-06-15)
Carlos Tassa, Stanley Y Shaw, Ralph Weissleder
ABSTRACT

Advances in our understanding of the genetic basis of disease susceptibility coupled with prominent successes for molecular targeted therapies have resulted in an emerging strategy of personalized medicine. This approach envisions risk stratification and therapeutic selection based on an individual's genetic makeup and physiologic state (the latter assessed through cellular or molecular phenotypes). Molecularly targeted nanoparticles can play a key role in this vision through noninvasive assessments of molecular processes and specific cell populations in vivo, sensitive molecular diagnostics, and targeted delivery of therapeutics. A superparamagnetic iron oxide nanoparticle with a cross-linked dextran coating, or CLIO, is a powerful and illustrative nanoparticle platform for these applications. These structures and their derivatives support diagnostic imaging by magnetic resonance (MRI), optical, and positron emission tomography (PET) modalities and constitute a versatile platform for conjugation to targeting ligands. A variety of conjugation methods exist to couple the dextran surface to different functional groups; in addition, a robust bioorthogonal [4 + 2] cycloaddition reaction between 1,2,4,5-tetrazene (Tz) and trans-cyclooctene (TCO) can conjugate nanoparticles to targeting ligands or label pretargeted cells. The ready availability of conjugation methods has given rise to the synthesis of libraries of small molecule modified nanoparticles, which can then be screened for nanoparticles with specificity for a specific cell type. Since most nanoparticles display their targeting ligands in a multivalent manner, a detailed understanding of the kinetics and affinity of a nanoparticle's interaction with its target (as determined by surface plasmon resonance) can yield functionally important insights into nanoparticle design. In this Account, we review applications of the CLIO platform in several areas relevant to the mission of personalized medicine. We demonstrate rapid and highly sensitive molecular profiling of cancer markers ex vivo, as part of detailed, individualized molecular phenotyping. The CLIO platform also facilitates targeted magnetic resonance and combined modality imaging (such as MR/PET/fluorescence/CT) to enable multiplexed measurement of molecular phenotypes in vivo for early diagnosis and disease classification. Finally, the targeted delivery of a photodynamic therapy agent as part of a theranostic nanoparticle successfully increased local cell toxicity and minimized systemic side effects.

MATERIALS
Product Number
Brand
Product Description

Dextran 60/70 for performance test, Dextran 60/70 European Pharmacopoeia (EP) Reference Standard
Dextran EP Reference Standard, European Pharmacopoeia (EP) Reference Standard
Dextran 70 for calibration, Dextran 70 European Pharmacopoeia (EP) Reference Standard
Dextran 250 for calibration, Dextran 250 European Pharmacopoeia (EP) Reference Standard
Dextran 40 for performance test, Dextran 40 European Pharmacopoeia (EP) Reference Standard
Dextran 10 for calibration, Dextran 10 European Pharmacopoeia (EP) Reference Standard
Dextran 40 for calibration, Dextran 40 European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Dextran from Leuconostoc mesenteroides, average mol wt 60,000-76,000
Supelco
Dextran, analytical standard, for GPC, 670,000
Supelco
Dextran, analytical standard, for GPC, 50,000
Supelco
Dextran, analytical standard, for GPC, 80,000
Supelco
Dextran, analytical standard, for GPC, 410,000
Supelco
Dextran, analytical standard, for GPC, 5,000
Supelco
Dextran, analytical standard, for GPC, 25,000
Supelco
Dextran from Leuconostoc mesenteroides, analytical standard, for GPC, Mw 12,000
Supelco
Dextran from Leuconostoc mesenteroides, analytical standard, for GPC, Mw 1,000
Supelco
Dextran from Leuconostoc mesenteroides, analytical standard, for GPC, Mw 670,000
Supelco
Dextran from Leuconostoc mesenteroides, analytical standard, for GPC, Mw 410,000
Sigma-Aldrich
Dextran from Leuconostoc spp., Mr ~70,000
Sigma-Aldrich
Dextran from Leuconostoc spp., Mr ~6,000
Sigma-Aldrich
Dextran from Leuconostoc spp., Mr ~40,000
Supelco
Dextran, analytical standard, for GPC, Set Mp 1,000-400,000
Sigma-Aldrich
Dextran from Leuconostoc mesenteroides, average mol wt 15,000-30,000
Sigma-Aldrich
Dextran solution from Leuconostoc mesenteroides, 20 % (w/w) (Autoclaved)
Sigma-Aldrich
Dextran from Leuconostoc mesenteroides, average mol wt 1,500,000-2,800,000
Sigma-Aldrich
Dextran from Leuconostoc mesenteroides, average mol wt 9,000-11,000
Dextran 1, Dextran 1 European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Dextran, enzymatic synth.
Sigma-Aldrich
Dextran from Leuconostoc mesenteroides, Mr ~60,000
Supelco
Dextran from Leuconostoc mesenteroides, for GPC, analytical standard, Mw 50,000