T908 Polymeric Micelles Improved the Uptake of Sgc8-c Aptamer Probe in Tumor-Bearing Mice: A Co-Association Study between the Probe and Preformed Nanostructures

被引:9
作者
Castelli, Romina [1 ]
Ibarra, Manuel [2 ]
Faccio, Ricardo [3 ]
Miraballes, Iris [4 ]
Fernandez, Marcelo [5 ]
Moglioni, Albertina [6 ]
Cabral, Pablo [1 ]
Cerecetto, Hugo [1 ]
Glisoni, Romina J. [7 ]
Calzada, Victoria [1 ]
机构
[1] Univ Republica, Fac Ciencias, Ctr Invest Nucl, Area Radiofarm, Montevideo 11400, Uruguay
[2] Univ Republica, Dept Pharmaceut Sci, Fac Chem, Montevideo 11800, Uruguay
[3] Univ Republica, Fac Quim, Area Fis, DETEMA, Montevideo 11800, Uruguay
[4] Univ Republica, Inmunol Clin BIOCLIN & Biotecnol, PoloTecnol PandoFac Quim, Montevideo 11800, Uruguay
[5] Univ Republica, Fac Ciencias, Ctr Invest Nucl, Lab Expt Anim, Montevideo 11400, Uruguay
[6] Univ Buenos Aires, Inst IQUIMEFA UBA CONICET, Fac Farm & Bioquim, Dept Farmacol, C1113AAD, Buenos Aires, DF, Argentina
[7] Univ Buenos Aires, Inst NANOBIOTEC UBA CONICET, Fac Farm & Bioquim, Dept Tecnol Farmaceut,CABA, C1113AAD, Buenos Aires, DF, Argentina
关键词
Sgc8-c aptamer; probe; polymeric micelles; liposomes; active targeting; DELIVERY-SYSTEMS; AQUEOUS-SOLUTIONS; DRUG; EXPRESSION; PTK7; THERMODYNAMICS; DYNAMICS; RELEASE; AGENT; GENE;
D O I
10.3390/ph15010015
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Aptamers are oligonucleotides that have the characteristic of recognizing a target with high affinity and specificity. Based on our previous studies, the aptamer probe Sgc8-c-Alexa647 is a promising tool for molecular imaging of PTK7, which is an interesting biomarker in cancer. In order to improve the delivery of this probe as well as create a novel drug delivery nanosystem targeted to the PTK7 receptor, we evaluate the co-association between the probe and preformed nanostructures. In this work, preformed pegylated liposomes (PPL) and linear and branched pristine polymeric micelles (PMs), based on PEO-PPO-PEO triblock copolymers were used: poloxamer F127(R) and poloxamines T1307(R) and T908(R). For it, Sgc8-c-Alexa647 and its co-association with the different nanostructures was exhaustively analyzed. DLS analysis showed nanometric sizes, and TEM and AFM showed notable differences between free- and co-associated probe. Likewise, all nanosystems were evaluated on A20 lymphoma cell line overexpressing PTK7, and the confocal microscopy images showed distinctness in cellular uptake. Finally, the biodistribution in BALB/c mice bearing lymphoma-tumor and pharmacokinetic study revealed an encouraging profile for T908-probe. All data obtained from this work suggested that PMs and, more specifically T908 ones, are good candidates to improve the pharmacokinetics and the tumor uptake of aptamer-based probes.
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页数:20
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