Aptamer vehiculization for therapy and molecular imaging

CALZADA V.; GLISONI RJ.; CASTELLI R.; BÁEZ J.; SICCO E.; FERNANDEZ LOMONACO M.; IBARRA M.; MOGLIONI A.G.; CABRAL P.; CERECETTO H.

Mar del Plata

Congreso; SAIC SAI SAFIS-NANOMED-ar 2018; 2018

SAIC-NANOMED-ar

Aptamers are oligonucleotides that have the characteristic of recognizing a target with high affinity and specificity. They have significant advantages in terms of size, production and modification and they are a versatile and low-cost tool for the development of new biotechnological platforms, as well as the development of therapy and imaging agents. The biggest challenges are to increase blood circulation and to prevent the degradation by nucleases. Sgc8c is an aptamer that recognizes the PTK7 receptor, described as a tumor target that has been previously studied, as a molecular imaging probe. Therefore, the goal of this work was the vehiculization of Sgc8c using different nanosystems to improve their delivery, as well as their stability. For this purpose, Sgc8c-(CH2)6-NH2 was firstly conjugated to NHS-Alexa647 fluorophore (Sgc8c-ALEXA) and its vehiculization was studied, using: (i) preformed pegylated liposomes (LPS), (ii) polymeric micelles (PMs) and (iii) hydroxypropyl-beta-cyclodextrin (HPβ-CD). The fluorescent probe was efficiently included in all the systems. The average particle size of loaded-systems was similar to that of the empty-systems. The Zeta-potential of the charged systems showed evidence that the probe would be included within the particles. After 24 hours, the 96% of LPS/probe was found in the release medium, so its effective release being manifested. The images by TEM obtained showed that the data fit in good agreement with DLS.Finally, the pharmacokinetic studies included the administration of the free-probe and the nanosystem/probe. Secondary pharmacokinetic parameters quantifying aptamer exposure and residence time were obtained through non-compartmental analysis. Although observations showed high intra- and interindividual variability, aptamer exposure was significantly greater for LPS/probe. Data obtained hitherto, would suggest that the preformed pegylated liposomes would increase the residence time of Sgc8c-ALEXA.