Development of a prototype of a theranostic system based on silica nanoparticles with immobilized fluorescent dyes and VEGF targeting ligand.

Abstract

Background. Administration of certain drugs causes undesirable effects associated with the systemic effect of the active substance on the entire body. Selective targeting of the drug to the affected tissue promotes a selective increase in the concentration of the substance in the area of interest, thereby reducing the systemic effect and enhancing the local therapeutic effect.Objective. Development of a targeted delivery system for theranostic agents using recombinant human vascular endothelial growth factor type A (rhVEGF-A121) as a targeting ligand.Design and method. To create the theranostic complex, commercially available reagents were used: the recombinant protein rhVEGF-A121 (cat.#: PSG140-10, LLC CyStorLab, Skolkovo, Russia) and fumed silica Aerosil (A-200, Degussa AG, Germany). The tosyl spacer that interconnects both components was synthesized in the laboratory. Protein conjugation with fluorophores was also carried out in-house. Indocyanine green (ICG; Sigma-Aldrich, USA) and rhodamine B (JSC Lenreaktiv, St. Petersburg, Russia) were taken for immobilization.Results. In the course of the work, functionalization of silica nanoparticles (SiNPs) with a tosyl spacer was carried out, conjugates of SiNPs with rhVEGF-A121 were synthesized, and theranostic constructs based on SiNPs were obtained, including rhVEGF-A121 as a targeting ligand, and ICG/Rhodamine B as a visualizing label.Conclusion. In the presented study, a prototype of a complex for targeted delivery of a theranostic agent to tissues with an active angiogenesis process, for example, to tumor and ischemic tissues, was developed. To solve the problem, we immobilized on the surface of SiNP a recombinant protein of human vascular endothelial growth factor (rhVEGF) to use as a guide ligand. Such a synthetic construct will help to deliver diagnostic and/ or medicinal substances packed in SiNP directly to cells that overexpress extracellular specific receptors of the VEGFR family. In subsequent in vivo experiments, delivery efficiency will be assessed by tissue accumulation of the fluorophores ICG and rhodamine B, which have been conjugated to the targeting ligand protein. The physicochemical characteristics of the obtained samples were studied by the methods of spectrophotometry and dynamic light scattering.