Biodistribution of a 153Gd-Folate Dendrimer, Generation = 4, in Mice With Folate-Receptor Positive and Negative Ovarian Tumor Xenografts

Konda, Sreenivas; Wang, Steven; Brechbiel, Martin W.; Wiener, Erik C.

doi:10.1097/00004424-200204000-00005

“…The first folate-targeted dendrimers described in the literature consisted of an ammonium-core polyamidoaminecore modified with folate as a targeting molecule and FITC as a fluorescent reporter. This targeted dendrimeric construct was then capped with succinic anhydride to render the remaining surface groups negatively charged to avoid nonspecific cell adsorption 92 . When introduced to FR + erythroleukemia cells, the folatedendrimer particle demonstrated biphasic uptake: rapid uptake within the first minutes (attributed to the dendrimer's initial binding to empty cell surface FR), followed by slower internalization attributed to endocytosis and recycling of FR back to the cell surface.…”

Section: Folate-targeted Dendrimersmentioning

confidence: 99%

“…Redesign of this folate-dendrimer construct to deliver an MRI contrast agent (gadolinium) provided good MRI contrast both in vitro and in vivo in FR + tumor xenografts 92 Quintana et al 93 then improved the folate-dendrimer design by capping the dendrimer surface amines with hydroxyl and acetamide groups, which enhanced projection of the targeting ligand away from the nanoparticle surface, permitting greater access to cell surface FR. These dendrimers demonstrated increased capture by KB cells and better drug delivery into the same cell type.…”

Section: Folate-targeted Dendrimersmentioning

confidence: 99%

Untitled

2016

IJPSR

0

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“…have intermediate numbers of terminal branches (COO-, OH) [61,62]. Even though dendrimer-based nanoparticles have been extensively researched in the past for their potential to be effective at chemotherapeutic drug delivery into solid tumors [63][64][65][66][67][68][69], including for folate receptor-targeted chemotherapeutic drug delivery [70][71][72][73][74], these investigations have been without emphasis on the optimal size range of 7 to 10 nanometers, the optimal density or the optimal exterior functionalization for effective, passively selective transvascular delivery, without risk of systemic toxicity, biophysical aspects that have important translational implications [1][2][3]7,8,25,26] (Table 1).…”

Section: Reviewmentioning

confidence: 99%

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

Sarin

¹

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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“…By contrast, Kobayashi and Brechbiel report that, by conjugating gadolinium to dendrimers, the unique properties of these polymers, such as exquisite size control, allowed selective targeting and imaging of the kidney, vascular, liver, or tumors [159]. Of note, tumor specific targeting and accumulation of gadolinium contrast agents is possible by use of either the folate receptor [165] or TAAs [159]. A drawback of the initial PAMAM-based MR contrast agents was their long residence time in the body; this problem, however, can be met by modifying both the surface properties [106] and basic chemical composition of the dendrimer.…”

Section: Towards Clinical Use: Mri Imaging Agentsmentioning

confidence: 99%

Dendrimers in Cancer Treatment and Diagnosis

Sampathkumar

¹

,

Yarema

²

2003

Nanotechnologies for the Life Sciences

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The sections in this article are Overview Introduction Basic Properties and Applications of Dendrimers Structural Features and Chemical and Biological Properties Basic Features of Dendritic Macromolecules are Inspired by Nature Comparison of the Properties of Dendrimers and Conventional Synthetic Polymers Comparison of the Properties of Dendrimers and Proteins (a Biological Polymer) Dendritic Macromolecules Possess a Wealth of Possible Applications Methods for Dendrimer Synthesis History and Basic Strategies Cascade Reactions are the Foundation of Dendrimer Synthesis Dendrimer Synthesis has Expanded Dramatically in the Past Two Decades Strategies, Cores, and Building Blocks for Dendritic Macromolecules Dendrimers are Constructed from Simple “Building Blocks” The Synthesis of Dendrimers Follows Either a Divergent or Convergent Approach Heterogeneously‐functionalized Dendrimers Basic Description and Synthetic Considerations Glycosylation is an Example of Surface Modification with Multiple Bioactivities Dendrimers in Drug Delivery Dendrimers are Versatile Nano‐devices for the Delivery of Diverse Classes of Drugs Dendritic Drug Delivery: Encapsulation of Guest Molecules Dendrimers have Internal Cavities that can Host Encapsulated Guest Molecules Using Dendrimers for Gene Delivery Release of Encapsulated “Pro‐drugs” Covalent Conjugation Strategies Dendrimers Overcome many Limitations Inherent in Polymeric Conjugation Strategies Dendrimer Conjugates can be Used as Vaccines Release of Covalently‐delivered “Pro‐drugs” Fine‐tuning Dendrimer Properties to Facilitate Delivery and Ensure Bioactivity Delivery Requires Avoiding Non‐specific Uptake “Local” Considerations: Contact with, and Uptake by, the Target Cell Drug Delivery: Ensuring the Biocompatibility of Dendritic Delivery Vehicles Biocompatibility Entails Avoiding “Side Effects” such as Toxicity and Immunogenicity Water Solubility and Immunogenicity Inherent and Induced Toxicity Dendrimers in Cancer Diagnosis and Treatment Dendrimers have Attractive Properties for Cancer Treatment Dendrimer‐sized Particles Passively Accumulate at the Sites of Tumors Multifunctional Dendrimers can Selectively Target Biomarkers found on Cancer Cells Methods for Targeting Specific Biomarkers of Cancer Targeting by Folate, a Small Molecule Ligand Targeting by Monoclonal Antibodies Dendrimers in Cancer Diagnosis and Imaging Labeled Dendrimers are Important Research Tools for Biodistribution Studies Towards Clinical Use: MRI Imaging Agents Steps Towards the Clinical Realization of Dendrimer‐based Cancer Therapies The Stage is now set for Dendrimer‐based Cancer Therapy Boron Neutron Capture Therapy Innovations Promise to Speed Progress “Mix‐and‐Match” Strategy of Bifunctional Dendritic Clusters Towards Therapeutic Exploitation of Glycosylation Abnormalities found in Cancer Towards Targeting Metabolically‐engineered Carbohydrate Epitopes Concluding Remarks Acknowledgments

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Biodistribution of a 153Gd-Folate Dendrimer, Generation = 4, in Mice With Folate-Receptor Positive and Negative Ovarian Tumor Xenografts

Abstract: Biodistribution studies confirm previous MRI findings and show that the accumulation of the folate-dendrimer requires the expression of the hFR.

Cited by 93 publications

References 19 publications

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

Dendrimers in Cancer Treatment and Diagnosis

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