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.

During last decades multiple therapeutic approaches have been explored for improved management of peritoneally disseminated malignancies – a grim condition known as peritoneal carcinomatosis (PC). Intraperitoneal administration can be used to achieve elevated local concentration and extended half-life of the drugs in the peritoneal cavity to improve their anticancer efficacy. However, IP-administered chemotherapeutics have a short residence time in the IP space, and are not tumor selective. An increasing body of work suggests that functionalization of drugs and nanoparticles with targeting peptides increases their peritoneal retention and provides a robust and specific tumor binding and penetration that translates into improved therapeutic response. Here we review a progress in affinity targeting of intraperitoneal anticancer compounds, imaging agents and nanoparticles with tumor homing peptides. We review classes of tumor homing peptides relevant for PC targeting, payloads for peptide-guided precision delivery, applications for targeted compounds and the effects of nanoformulation of drugs and imaging agents on affinity-based tumor delivery.

The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-Covid-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of Mannose Receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of Covid-19 pathology and immunity to SARS-CoV-2.