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End-group distributions of multiple generations of spin-labeled PAMAM dendrimers.

ABSTRACT: Dendrimers are attractive templates to display functional molecular components. Since the behavior of dendrimer systems can depend greatly on the accessibility of these molecular components to the external environment, and on the spatial arrangement of functional groups attached to the dendrimer terminal branches (end-groups), techniques to determine the locations of end-groups are highly desirable. In this report, we describe a method to analyze the EPR spectra of multiple generations of poly(amidoamine) (PAMAM) dendrimers which have spin-labels attached to end-groups in variable percentages of the total number of available sites. The spectra are treated as a convolution of a narrow spin-label spectrum and a variable line broadening function. Trends in the parameters that describe the best-fit line broadening function with spin-label loading reveal the spatial arrangements and homogeneity of spin environments of the labels. We observe a shift in the end-group distribution from generation 3 (G(3)) to G(4) dendrimers that indicates a change in morphology from an open, extended structure to a more dense, compact arrangement.

SUBMITTER: Sebby KB

PROVIDER: S-EPMC3424105 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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End-group distributions of multiple generations of spin-labeled PAMAM dendrimers.

Sebby Karl B KB Walter Eric D ED Usselman Robert J RJ Cloninger Mary J MJ Singel David J DJ

The journal of physical chemistry. B 20110406 16

Dendrimers are attractive templates to display functional molecular components. Since the behavior of dendrimer systems can depend greatly on the accessibility of these molecular components to the external environment, and on the spatial arrangement of functional groups attached to the dendrimer terminal branches (end-groups), techniques to determine the locations of end-groups are highly desirable. In this report, we describe a method to analyze the EPR spectra of multiple generations of poly(a ...[more]

PMID: 21469686

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Project description:Dendrimers are being explored in many preclinical studies as drug, gene, and imaging agent delivery systems. Understanding their detailed organ, tissue, cellular uptake, and retention can provide valuable insights into their effectiveness as delivery vehicles and the associated toxicity. This work explores a fluorescence-quantification based assay that enables simultaneous quantitative biodistribution and imaging of dendrimers with a single agent. We have labeled an ethylenediamine-core generation-4 hydroxyl-terminated poly(amidoamine) (PAMAM) dendrimer using the fluorescent photostable, near-IR cyanine dye (Cy5) and performed quantitative and qualitative biodistribution of the dendrimer-Cy5 conjugates (D-Cy5) in healthy neonatal rabbits and neonatal rabbits with cerebral palsy (CP). The biodistribution of D-Cy5 and free Cy5 dye was evaluated in newborn rabbits, based on the developed quantification methods using fluorescence spectroscopy, high-performance liquid chromatography (HPLC), and size exclusion chromatography (SEC) and supported by microscopic imaging. The uptake was assessed in the brain, heart, liver, lungs, kidneys, blood serum, and urine. Results obtained based on these three independent methods are in good agreement and indicate the fast renal clearance of D-Cy5 and free Cy5 with relatively higher organs accumulation of the D-Cy5 conjugate. Following systemic administration, the D-Cy5 mainly accumulated in kidneys and bladder at 24 h. The quantitative biodistribution is in good agreement with previous studies based on radiolabeling. These methods for dendrimers quantification are easier and more practical, provide excellent sensitivity (reaching 0.1 ng per gram of tissue), and allow for quantification of dendrimers in different organs over longer time periods without concerns for radioactive decay, while also enabling tissue and cellular imaging in the same animal. In kits with fetal-neuroinflammation induced CP, there was a significantly higher uptake of D-Cy5 in the brain, while biodistribution in other organs was similar to that of healthy kits.

Dataset Information

End-group distributions of multiple generations of spin-labeled PAMAM dendrimers.

Publications

End-group distributions of multiple generations of spin-labeled PAMAM dendrimers.

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