Fluorescent BAPAD Dendrimeric Antigens Are Efficiently Internalized by Human Dendritic Cells

Abstract

A new fluorescent dendrimeric antigen (DeAn) based on a dendron with amoxicilloyl terminal groups was synthesized. The synthesis was carried out using a novel class of all-aliphatic polyamide dendrimer (BisAminoalkylPolyAmide Dendrimers, or BAPAD) involving the direct condensation of 3,3′-diazidopivalic acid as a building block. Iterative azide reduction/amide formation increases the dendrimer generation. The BAPAD dendrimer was designed with a cystamine core. Reduction of the disulfide bond allows the incorporation of BAPAD dendrons into a 1,8-naphthalimide functionalized with a maleimide group. The fluorescence properties of DeAn were studied in PBS and compared with the properties of an equivalent dendron possessing amino-terminal groups. Both molecules shown high fluorescence quantum yields in PBS and could readily be visualized by fluorescence microscopy. DeAn was used as a synthetic antigen in a biomedical assay that tests their potential as an amoxicillin carrier in drug internalization by dendritic cells (DC) from tolerant and allergic patients. Cytometry data suggest that the dendrons are non-toxic and easily internalized by DCs, while confocal microscopy images indicate that the compounds are preferentially accumulated in the cytoplasm. These results indicate that BAPAD dendrons are good candidates for synthetic scaffolds for biomedical applications.

Dendritic platforms for biomimicry and biotechnological applications

“…Results revealed these dendrons to be non-toxic and they could be easily internalized by dendritic cells. It was concluded that BAPAD dendrons could serve as efficient candidates for synthetic scaffolds for such applications [53]. Thus, dendrimers have emerged as one of the promising technique for specific delivery of antigens.…”

Slightly congested amino terminal dendrimers. The synthesis of amide-based stable structures on a large scale

“…Thus, dendrons based on this structure were used as platforms in diagnosis tests of allergic reactions to drugs. 24 The dendritic moieties have also been used as scaffolds for the covalent immobilization of bioactive peptides in titanium disks, increasing the biocompatibility of oral titanium implants. 25 Furthermore, the insertion of these dendritic scaffolds into Pt(II) complexes endows them with unique properties such as aqueous solubility, shielding from quenching by dioxygen, and binding to bacterial surfaces, opening the way for the development of new phosphorescent biomarkers with promising properties.…”

Synthesis of Amino Terminal Clicked Dendrimers. Approaches to the Application as a Biomarker

“…Using a divergent approach, this novel polyamide dendrimer (BAPAD) was synthetized based on a 3,3′-diaminopivalic acid scaffold . Their excellent stability allowed the use of such dendrimers for different bio-applications. , However, despite the versatility of the system, the maximum generation of the amino terminal dendrimer obtained was generation 3, which contains 16 peripheral amino groups. , This could be explained by a dramatic decrease in the reactivity of the azide groups caused by a backfolding of these surface groups. This effect has been previously observed and is more pronounced when the synthesis of the dendrimer is performed in a divergent way .…”

“…16 Their excellent stability allowed the use of such dendrimers for different bio-applications. 17,18 However, despite the versatility of the system, the maximum generation of the amino terminal dendrimer obtained was generation 3, which contains 16 peripheral amino groups. 16,19 This could be explained by a dramatic decrease in the reactivity of the azide groups caused by a backfolding of these surface groups.…”