Bivalent Peptide- and Chelator-Containing Bioconjugates as Toolbox Components for Personalized Nanomedicine.

Abstract

While personalized therapy bears an enormous potential in cancer therapy, the development of flexible, tailorable delivery systems remains challenging. Here, we present a "tool-kit" of various avidin-based bioconjugates (BCs) for the preparation of personalized delivery systems. Corresponding BCs were synthesized using the self-assembly of avidin with various biotinylated ligands, such as one cationic glycodendrimer for dendriplex adsorption and two functional ligands for imaging (glycodendrimers with DOTA or NOTA units) or targeting (biotinylated PEG decorated with ligands). Substituting antibodies for targeting small molecules were coupled to biotin-PEG compounds for addressing the folate receptor (FR), epidermal growth factor receptor (EGFR), and prostate-specific membrane antigen (PSMA). After successful characterization and proof of good storage and redispersion properties of BCs, cytotoxicity assays and first in vivo imaging studies with 99mTc-complexing bioconjugates provide evidence that these BCs and their avidin analogues can be used as tool-kit components in theranostic systems for personalized medicine.

• Authors: Jennifer Daeg, Xiaoying Xu, Lingzhou Zhao, Susanne Boye, Andreas Janke, Achim Temme, Jinhua Zhao, Albena Lederer, Brigitte Voit, Xiangyang Shi, Dietmar Appelhans
• Journal: Biomacromolecules (Biomacromolecules) Vol. 21 Issue 1 Pg. 199-213 (01 13 2020) ISSN: 1526-4602 [Electronic] United States
• PMID: 31619036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Surface
• Chelating Agents
• Contrast Media
• Dendrimers
• Heterocyclic Compounds, 1-Ring
• Peptides
• Avidin
• 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
• Polyethylene Glycols
• 1,4,7-triazacyclononane-N,N',N''-triacetic acid
• Biotin
• Folic Acid
• EGFR protein, human
• ErbB Receptors
• FOLH1 protein, human
• Glutamate Carboxypeptidase II

Topics

• Animals
• Antigens, Surface (metabolism)
• Avidin (chemistry)
• Biotin (chemistry)
• Chelating Agents (chemistry)
• Contrast Media (chemistry)
• Dendrimers (chemistry)
• Diagnostic Imaging
• ErbB Receptors (metabolism)
• Folic Acid (chemistry)
• Glutamate Carboxypeptidase II (metabolism)
• HEK293 Cells
• Heterocyclic Compounds, 1-Ring (chemistry)
• Humans
• Male
• Mice, Inbred BALB C
• Molecular Targeted Therapy (methods)
• Nanomedicine (methods)
• Peptides (chemistry)
• Polyethylene Glycols (chemistry)
• Prostatic Neoplasms (drug therapy)
• Xenograft Model Antitumor Assays