Synthesis of Metal‐Carbonyl–Dendrimer–Antibody Immunoconjugates: Towards a New Format for Carbonyl Metallo Immunoassay

Fischer‐Durand, Nathalie; Salmain, Michèle; Rudolf, Bogna; Vessières, Anne; Zakrzewski, Janusz; Jaouen, Gérard

doi:10.1002/cbic.200300800

“…Therefore, to maximize drug loading while minimizing the deleterious effects on the biological integrity of the host antibody, an attractive approach is to use a linker molecule, such as a dendrimer, that can be highly conjugated (or internally loaded) with drug while modifying only a single site on the surface of the antibody [147]. Methodology to covalently attach antibodies to dendrimers that preserve the activity of the antigen-antibody binding site [148,149], e.g., by chemical modification of their carbohydrates and subsequent linkage to PAMAM [150], has opened the door for the inclusion of dendrimers in immunotherapy [151,152], thereby enhancing the future prospects of this chronically ''almost-there'' strategy. The synthetic ability to attach both a tumor-targeting antibody and a potent payload of anticancer drugs to the same dendritic molecule provides a platform for multifunctional nano-scale drug delivery devices (Fig.…”

Section: Targeting By Monoclonal Antibodiesmentioning

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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“…This is a preliminary work, as our final objective is to label AV with metallocarbonyl PAMAM dendrimers, as part of our ongoing development of Carbonyl Metallo Immuno Assay. [8] …”

Section: Introductionmentioning

confidence: 97%

The Use of Glycidol to Introduce Aldehyde Functions Into Proteins – Application to the Fluorescent Labelling of Bovine Serum Albumin and Avidin

Heldt¹,

Fischer‐Durand²,

Salmain³

et al. 2007

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The reactions between 2,3‐epoxypropan‐1‐ol (glycidol) and either the nonglycosylated protein bovine serum albumin (BSA) or the glycoprotein avidin (AV) allowed the successful introduction of diol groups through the addition of some of the proteins' nucleophilic residues to the epoxide ring. The extent of glycolation could be readily tuned by varying the reaction time, the pH of reaction and the concentration of glycidol. Treatment of the stable protein‐diol intermediates with sodium periodate resulted in the generation of reactive aldehyde functionalities through the oxidation of the glycol moieties. At this step, the amount of generated aldehydes could also be modulated by changing the time and/or pH of oxidation. As an application, both formylated proteins were successfully labelled with the hydrazide‐containing fluorescent dye Lucifer Yellow CH (LyCH), affording highly fluorescent conjugates. Mild oxidation of the avidin‐diol left untouched glycol moieties that contributed to greatly enhance water solubility in the avidin‐LyCH bioconjugates. In certain cases the avidin‐LyCH conjugates retained a good affinity for biotin, as shown in a competitive binding assay. Glycidol thus appears to be an attractive low‐cost reagent for protein chemical activation aimed at further coupling of amine‐containing species.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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“…The ethylenic bond of the maleimidato ligand in these complexes is readily attacked by nucleophiles such as thiols, amines or imidazoles. These reactions can be used to introduce IR-detectable moieties on peptides and proteins with potential applications in immunoassays [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%