Quantitative STEM and EFTEM Characterization of Dendrimer-Based Nanoparticles Used in Magnetic Resonance Imaging and Drug Delivery

Sousa, Alioscka A.; Aronova, MA; Wu, Haitao; Sarin, Hemant; Griffiths, GL; Leapman, Richard D.

doi:10.1017/s143192760808224x

Cited by 2 publications

(2 citation statements)

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“…Since the sizes of hydrated dendrimer generations, measured by small-angle X-ray scattering (SAXS) [ 51 ] and small-angle neutron scattering (SANS) [ 52 ], are similar to the sizes of respective dehydrated dendrimer generations measured by TEM [ 37 ], we were able to use ADF STEM to image Gd-G5 and higher generation Gd-dendrimers: these Gd-dendrimer generations possessed masses heavy enough to be visualized by ADF STEM [ 46 , 53 ]. ADF STEM images of Gd-G5 through Gd-G8 dendrimers demonstrated uniformity in particle size, shape and density within any particular dendrimer generation (Figure 1C ).…”

Section: Resultsmentioning

confidence: 98%

Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells

et al. 2008

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BackgroundEffective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells.MethodsMagnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured in vivo with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed ex vivo with fluorescence imaging.ResultsWe found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells.ConclusionThe therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives.

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Section: Resultsmentioning

confidence: 98%

Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells

et al. 2008

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“…chelates on the exterior remain within the 7 to 10 nanometer size range following functionalization, which is the case for the range of Gd-DTPA-G5 dendrimer (80-85 kDa; Diameter est at 7.5 nm) [3,8,28,29,76] (Table 1). In the case of the Gd-DTPA-G5 dendrimer-linker-Doxorubicin (85 kDa), its diameter as measured by dynamic light scattering in serum albumin protein-free solution, is at 9 nanometers [3] (Table 1), due to the linker attachment of Doxorubicin to the exterior, which protrudes~1.5 nanometers above the nanoparticles surface.…”

Section: Reviewmentioning

confidence: 96%

Translational theranostic methodology for diagnostic imaging and the concomitant treatment of malignant solid tumors

Sarin

2015

Neurovascular Imaging

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Pathologic hyperpermeability exists in the spectrum of disease states, including neuro-ischemic, neuro-inflammatory and neuro-oncological. To-date the characterization of disease pathology with T 1 -weighted quantitative dynamic contrast-enhanced magnetic resonance imaging has relied on the study of modeled microvascular parameters such as diseased tissue transvascular flow rates of small molecule paramagnetic imaging agents with short plasma half-lives, based on which it is difficult to assess the specific nature of the disease state. Another type of T 1 -weighted quantitative dynamic contrast-enhanced magnetic resonance imaging involves the use of paramagnetic heavy metal-chelated dendrimer nanoparticles that possess longer plasma half-lives with pre-determined molar relaxivities to quantitatively image concentration of macromolecular contrast agent accumulation over time in hyperpermeable pathology such as solid tumor tissue with the important advantage of concomitantly treating the pathology, which, in recent years, has been shown to be possible with the use of optimally-sized theranostic dendrimer nanoparticles in the 7 to 10 nanometer size range that are functionalized biocompatibly with a small molecule therapeutic. In this focused review, this translational theranostic methodology for quantitative dynamic contrast-enhanced magnetic resonance imaging and the concomitant treatment of malignant solid tumors with optimally designed theranostic nanoparticles within the 7 to 10 nanometer size range is discussed in context of fine-tuning its suitability for the study and treatment of other disease states with pathologic hyperpermeability and without.

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Quantitative STEM and EFTEM Characterization of Dendrimer-Based Nanoparticles Used in Magnetic Resonance Imaging and Drug Delivery

Abstract: Extended abstract of a paper presented at Microscopy and Microanalysis 2008 in Albuquerque, New Mexico, USA, August 3 – August 7, 2008

Cited by 2 publications

References 5 publications

Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells

Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells

Translational theranostic methodology for diagnostic imaging and the concomitant treatment of malignant solid tumors

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