Artigo de peri??dico
Engineering of galectin-3 for glycan-binding optical imaging
Registro en:
0006-291X
3
521
10.1016/j.bbrc.2019.10.161
0000-0002-0029-7313
50.18
62.50
Autor
DE LEO, THAIS C.
SANTOS, SOFIA N. dos
ANDRADE, CAMILLO D.C.
RICCI, EDUARDO
TURATO, WALTER M.
LOPES, NORBERTO P.
OLIVEIRA, RALPH S.
BERNARDES, EMERSON S.
DIAS-BARUFFI, MARCELO
Resumen
Galectin-3 (Gal-3) is a multifunctional glycan-binding protein that participates in many pathophysiological
events and has been described as a biomarker and potential therapeutic target for severe disorders,
such as cancer. Several probes for Gal-3 or its ligands have been developed, however both the
pathophysiological mechanisms and potential biomedical applications of Gal-3 remain not fully assessed.
Molecular imaging using bioluminescent probes provides great sensitivity for in vivo and in vitro analysis
for both cellular and whole multicellular organism tracking and target detection. Here, we engineered a
chimeric molecule consisting of Renilla luciferase fused with mouse Gal-3 (RLuc-mGal-3). RLuc-mGal-3
preparation was highly homogenous, soluble, active, and has molecular mass of 65,870.95 Da. This
molecule was able to bind to MKN45 cell surface, property which was inhibited by the reduction of Gal-3
ligands on the cell surface by the overexpression of ST6GalNAc-I. In order to obtain an efficient and stable
delivery system, RLuc-mGal-3 was adsorbed to poly-lactic acid nanoparticles, which increased binding to
MKN45 cells in vitro. Furthermore, bioluminescence imaging showed that RLuc-mGal-3 was able to
indicate the presence of implanted tumor in mice, event drastically inhibited by the presence of lactose.
This novel bioluminescent chimeric molecule offers a safe and highly sensitive alternative to fluorescent
and radiolabeled probes with potential application in biomedical research for a better understanding of
the distribution and fate of Gal-3 and its ligands in vitro and in vivo. Coordena????o de Aperfei??oamento de Pessoal de N??vel Superior (CAPES) Conselho Nacional de Desenvolvimento Cient??fico e Tecnol??gico (CNPq) CAPES: 88881.121165/2016-0 CNPq: 311947/2015-8