Antibodies can be spontaneously loaded onto monosialoganglioside micelles containing oncological drugs

Abstract

Recently, we demonstrated that GM1 micelles transport paclitaxel and doxorubicin with high efficiency. Whenthis GM1-drugs complex is incubated with whole serum, albumin was the only one protein that binds spontaneouslyto form GM1-drug-albumin complex. Here, we show that, under specific physicochemical conditions, these micellesinteract with antibodies forming GM1-IgG complexes. The load of IgG in GM1 reaches a maximum at ratios of 1/4(w / w) incubating to 4.5 and preheating the micelles of GM1 at 55-60°C. The IgG of the GM1-IgG complex obtainedunder these experimental conditions retains the biological activity against the soluble and cellular antigens and is notdisplaced from the micelles in the presence of albumin, the main competitive binding protein.Treatment of GM1-IgG with pepsin, does not show the breakage of the IgG like control of free IgG, suggesting thatIgG is deeply bound into GM1, probably via Fc. Moreover, the presence of 1 M NaCl does not prevent neither dissociatethe complex, suggesting the hydrophobic nature of the interaction. The DLS and TEM results shows that GM1-IgGcomplexes have sizes significantly higher than those of GM1 micelles; this is directly related to the amount of IgGloaded. On the other hand GM1-IgG complex also retain the ability to encapsulate oncological drugs, but, an adequatesequence must be followed during the preparation, in order to obtain efficient GM1-drug-IgG ternary complexes. Moreover, the presence of IgG into GM1-oncological drugs complex do not affect the release or the citotoxic activity ofthe encapsulated molecules such as Ptx or Doxo.Fil: Garro, Ariel Gustavo. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Alasino, Roxana Valeria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Leonhanrd, Victoria. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; ArgentinaFil: Heredia, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Beltramo, Dante Miguel. Provincia de Córdoba. Ministerio de Ciencia y Técnica. Centro de Excelencia en Productos y Procesos de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

    Similar works