Effects of N-acetyl-glucosamine-coated glycodendrimers as biological modulators in the B16F10 melanoma model in vivo

Abstract

following a re-evaluation of controversial results of Professor K. Bezouska on NKR-P1 (rat and mouse receptors) interactions with carbohydrates, we need to correct some statements of this paper and the interpretation of some results consequent to these statements (which were based on published data by Professor K. Bezouska considered still valid at the time of preparation and publication of this paper).At present, we need to consider the following statment as erroneous:-the NKR-P1 receptor is a high affinity receptor for various oligosaccharides which were considered mimetics of putative ligands for this receptor (as previously reported in literature);-PAMAM-GlcNAc 8 glycodendrimer has high affinity and selectivity for the NKR-P1 receptor.Instead, the effects of PAMAM-GlcNAc 8 reported in this paper, modulating the tumor biology and immune response, have to be re-interpreted: as the result of not exclusive interaction of glycodendrimers with NKR-P1 receptor and NK cells but as the possible result of interactions with a wider panel of cells and recep-

Re-evaluation of the involvement of NK cells and C-type lectin-like NK receptors in modulation of immune responses by multivalent GlcNAc-terminated oligosaccharides

“…As stated above, several previous studies interpreted in vivo effects of polyvalent dendrimers on an assumption that they were based on stimulation of NK cells (via NKR-P1) by these synthetic complex saccharides [16][17][18][19]. However, our present data indicate that these effects are probably due to interactions with other cell types (via so far unidentified receptors).…”

“…Despite the fact that original binding experiments were performed using rat derived recombinant proteins, the concept was broadened to mouse model, although binding of mouse C-type lectin-like receptors to the saccharide structures has never been published. Importantly, marked anti-tumor effects of synthetic glycoconjugates were observed in mice, which was interpreted in terms of activation of NK cells (an extrapolation of the rat-based data) [16][17][18][19][20].…”

“…examine multivalent saccharide binding to (a) recombinant rat NKR-P1A and mouse NKR-P1C proteins and (b) to various leukocyte subpopulations. As a model oligosaccharide compound we used N-acetyl-d-glucosamine-coated octabranched polyamidoamine dendrimer (GN8P) and N-acetyl-d-glucosaminecoated tetrabranched polyamidoamine dendrimer fluorescently labeled (GN4P-A), as already described in the literature [16][17][18][19]21].…”

Biomedical Nanoparticles: Overview of Their Surface Immune-Compatibility

“…For instance, N-acetyl-glucosamine-coated G1 PAMAMs administered in mice bearing subcutaneous melanoma model, decrease tumor growth and increase mice survival. These results were accompanied by an increase of CD69+ cells in the spleen and the tumor tissue, associated to the up-regulation of IL-1h, IFN-g, TNF-a and IL-2 [42]. Another indication of such phenomenon is provided by the over-expression of pro-inflammatory chemokines and cytokines, namely MIP-1a, MIP-1h, IL-8, TNF-a, IL-1h and IL-6 induced in human dendritic cells and macrophages by glucosamine-modified G3.5 PAMAMs [43].…”

Novel therapeutic mechanisms determine the effectiveness of lipid-core nanocapsules on melanoma models

“…8,9 Different drug-delivering systems such as liposomes, [10][11][12][13] dendrimers, 14,15 polymersomes, 16,17 and carbon-based nanoparticles 18,19 have been tested, but until now, only liposomes and albumin nanoparticles containing anticancer drugs have been used clinically. [20][21][22] Polymeric nanocarriers such as multifunctional lipidcoated nanoparticles 23 and polymeric nanocapsules 24 have encouraging therapeutic applications of nanodrug delivery systems, especially as carriers for anticancer drugs into solid tumors.…”