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Memona Khan,* Khaoula Cherni,* Rawdha Dekhili, Jolanda Spadavecchia CNRS, UMR 7244, NBD-CSPBAT, Laboratory of Chemistry, Structures and Properties of Biomaterials and Therapeutic Agents University Paris 13, Sorbonne Paris Nord, Bobigny, France*These authors contributed equally to this workCorrespondence: Rawdha Dekhili; Jolanda Spadavecchia, Email rawdhadekhilichimiste@gmail.com; jolanda.spadavecchia@univ-paris13.fr; jolanda.spadavecchia@gmail.comIntroduction: The aim of this study is focused on the development of theranostic hybrid nanovectors based on gold-doxorubicin (DOX)-gemcitabine (GEM) complexes and their active targeting with Galectin-1 (Gal-1) as a promising therapeutic and prognostic marker in cancer.Methods: For this purpose, a gold salt (HAuCl4) interacts with antitumor drugs (DOX; GEM) by chelation and then stabilizes with dicarboxylic acid-terminated polyethylene glycol (PEG) as a biocompatible surfactant. The proposed methodology is fast and reproducible, and leads to the formation of a hybrid nanovector named GEM@DOX IN PEG-AuNPs, in which the chemo-biological stability was improved. All synthetic chemical products were evaluated using various spectroscopic techniques (Raman and UV–Vis spectroscopy) and transmission electron microscopy (TEM).Results: To conceive a therapeutic application, our hybrid nanovector (GEM@DOX IN PEG-AuNPs) was conjugated with the Galectin-1 protein (Gal-1) at different concentrations to predict and specifically recognize cancer cells. Gal-1 interacts with GEM@DOX in PEG-AuNPs, as shown by SPR and Raman measurements. We observed both dynamic variation in the plasmon position (SPR) and Raman band with Gal-1 concentration.Discussion: We identified that GEM grafted electrostatically onto DOX IN PEG-AuNPs assumes a better chemical conformation, in which the amino group (NH3+) reacts with the carboxylic (COO−) group of PEG diacide, whereas the ciclopenthanol group at position C-5’ reacts with NH3+ of DOX.Conclusion: This study opens further way in order to built “smart nanomedical devices” that could have a dual application as therapeutic and diagnostic in the field of nanomedicine and preclinical studies associated.Keywords: gold-complex, gemcitabine, doxorubicin, galectin-1 protein, Raman spectroscopy, nanovector, diagnostic, biomarkers

Aptamers are small biomolecules composed of 20-100 nucleotides that recognize target molecules in three-dimensional structures. These natural targeting molecules have attracted interest in the biomedical field as biomarkers for cancer diagnostics. In this study, we investigated the interaction of a characteristic aptamer with its target protein, Cu, Zn superoxide dismutase (SOD 4), on a gold nanoparticle (AuNP) surface under experimental conditions. For this purpose, we applied two protocols to coat SOD 4 aptamer (APT) on the nanoparticle surface: carbodiimide chemistry (EDC/NHS) (Method ON) and a complexation methodology (Method IN). The nano-aptamer's interactions with SOD 4 were detected by UV-vis absorption and Raman spectroscopy in a range of protein concentrations (from 1 μM to 50 nM). We believe that the interaction is heavily dependent on the nature of the biomarker (SOD 4) and also on the steric arrangement of the aptamer on the gold nanoparticle surface. The lowest detectable concentration (limit of detection, LOD) was about 2 nM for APT IN PEG-AuNPs and 8 nM for APT ON PEG-AuNPs. For the first time, we demonstrated a very sensitive detection of SOD 4 in the nanomolar concentration range with new ways of biosensor synthesis (APT IN and ON), providing a very strong tool to understand the effect of aptamer conformation to detect SOD 4., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)