Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Biomimetic System Based on Reconstituted Macrophage Membranes for Analyzing and Selection of Higher-Affinity Ligands Specific to Mannose Receptor to Develop the Macrophage-Focused Medicines

Version 1 : Received: 21 August 2023 / Approved: 25 August 2023 / Online: 25 August 2023 (07:51:34 CEST)

A peer-reviewed article of this Preprint also exists.

Zlotnikov, I.D.; Kudryashova, E.V. Biomimetic System Based on Reconstituted Macrophage Membranes for Analyzing and Selection of Higher-Affinity Ligands Specific to Mannose Receptor to Develop the Macrophage-Focused Medicines. Biomedicines 2023, 11, 2769. Zlotnikov, I.D.; Kudryashova, E.V. Biomimetic System Based on Reconstituted Macrophage Membranes for Analyzing and Selection of Higher-Affinity Ligands Specific to Mannose Receptor to Develop the Macrophage-Focused Medicines. Biomedicines 2023, 11, 2769.

Abstract

Progress in macrophage research is crucial for numerous applications in medicine, including cancer and infectious diseases. However, the existing methods to manipulate living macrophages are labor intense and inconvenient. Here we show that macrophage membranes can be reconstituted after storage for months at 4C, with their CD206 receptor selectivity and specificity being similar to that in the living cells. Then, we have developed a mannose ligand, specific to CD206, linked with PEG as IR spectroscopy marker to detect binding with the macrophage receptor. PEG was selected due to its unique adsorption band of C-O-C group at IR spectra, which does not overlap with other biomolecule’s spectroscopic feature. Next, competitive binding assay versus the PEG-bound ligand, has enabled selection of other higher-affinity ligands specific to CD206. Further, those higher-affinity ligands were used to differentiate activated macrophages in patient’s bronchoalveolar (BAL) or nasopharyngeal (NPL) lavage. CD206- control cells (HEK293T) showed only non-specific binding. Therefore, biochips based on reconstituted macrophage membranes as well as PEG-trimannoside as an IR spectroscopic marker, can be used to develop new methods facilitating macrophage research and macrophage-focused drug discovery.

Keywords

macrophage-based biochip; CD206; bronchoalveolar lavage; diagnostics

Subject

Biology and Life Sciences, Biology and Biotechnology

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