T908 POLYMERIC MICELLES IMPROVED THE UPTAKE OF SGC8C-ALEXA IN MICE BEARING LYMPHOMA TUMOR INDUCED USING A20-CELLS THAT OVEREXPRESS PTK7 RECEPTOR

CASTELLI R.; FERNANDEZ M.; SICCO E.; IBARRA M.; CERECETTO H. ; CALZADA V.; GLISONI RJ.

BUENOS AIRES

Congreso; Annual Meeting of Bioscience Societies 2021; 2021

SAIC-SAI-AAFE-NANOMED

Aptamers are oligonucleotides that have the characteristic of recognizing a target with high affinity and specificity. The greatest challenges include to overcome the degradation by endo- and exo-nucleases and to increase its blood circulation. Sgc8c is an aptamer that recognizes the PTK7 receptor, described as a tumor target that has been previously studied by our research group, as a molecular imaging probe. In this work, we studied the optimization of Sgc8c delivery, as well as its stability, using linear and branched polymeric micelles (PMs), based of PEO-PPO-PEO copolymers: poloxamer F127® and poloxamines T1307® and T908®. For it, Sgc8c-(CH2)6-NH2 was conjugated to Alexa647 fluorophore (Sgc8c-ALEXA, probe) and its co-association with different PMs was exhaustively analyzed. The majority size-populations of Sgc8c-ALEXA-PMs were between 11 and 32 nm at 25ºC by Dynamic Light Scattering (DLS). Zeta-potentials were moderately negative in all cases. TEM and AFM data fitted well with DLS and showed nanometric sizes with marked different morphology between free- and co-associated probe-PMs. Finally, the biodistribution and pharmacokinetic studies in BALB-c mice bearing lymphoma tumor induced using A20-cells,revealed an enhanced circulation time and marked uptake into tumor for Sgc8c-ALEXA-T908 PMs. All data obtained from this work, suggested that PEO- PPO-PEO based PMs and, more specificallythose PMs made of high molecular weight copolymer (~25 kDa), such as T908-based ones, are good candidates to improve the pharmacokinetics and the tumor uptake of Sgc8c-ALEXA in models of mice bearing tumor.