Design and Synthesis of Hybrid PEGylated Metal Monopicolinate Cyclam Ligands for Biomedical Applications
Authors: Jolanda Spadavecchia
Luca de Stefano
Stefania Filosa
Fatima Aouidat
Rosalba Moretta
Stella Donato
Rosarita Tatè
Zakaria Halime
Raphaël Tripier
Ilaria Rea
Journal: ACS Omega (2019)
Discipline: CHEMISTRY
Keywords: nanosystems; gold Au(III); copper Cu(II); nanoparticles; chelation
Affiliations: CNRS, UMR 7244, CSPBAT, Laboratoire de Chimie, Structures et Propriétés de Biomateriaux et d'Agents Therapeutiques Université Paris 13, 1 rue Chablis 93000, Sorbonne Paris Cité, 93000 Bobigny, France., Universitè de Brest, UMR-CNRS 6521/IBSAM, UFR Sciences et Techniques, 6 Avenue Victor le Gorgeu, C.S. 93837, 29238 Brest, France., Institute for Microelectronics and Microsystems, Unit of Naples, CNR, Via P. Castellino 111, 80131 Naples, Italy., Institute of Biosciences and Bioresources (IBBR), National Research Council (CNR), Naples, Italy-IRCCS, Neuromed, Via Università, 133, 80055 Pozzilli, Isernia, Italy., Institute of Genetics and Biophysics "Adriano Buzzati-Traverso", CNR, Via P. Castellino 111, 80131 Naples, Italy.

Abstract:  In this study, we report, for the first time, the synthesis of two original nanosystems, based on gold Au(III) and copper Cu(II): simple gold-copper nanoparticles (Cu0AuNPs) and enriched monopicolinate cyclam (L1)-Cu(II)-Au(III)-complex (L1@Cu2+AuNPs). The two nanomaterials differ substantially by the chelation or not of the Cu(II) ions during the NPs synthesis process. The two hybrid nanoparticles (Cu0AuNPs; L1@Cu2+AuNPs) were deeply studied from the chemical and physical point of view, using many different analytical techniques such as Raman and UV-vis spectroscopy, electron transmission microscopy, and dynamic light scattering. Both nanosystems show morphological and good chemical stability at pH 4 values and in physiological conditions during 98 h. Undifferentiated and neural differentiated murine embryonic stem cells were used as a model system for in vitro experiments to reveal the effects of NPs on these cells. The comparative study between Cu0AuNPs and L1@Cu2+AuNPs highlights that copper chelated in its +2 oxidation state in the NPs is more functional for biological application. 

Retracted: No

PubPeer comments:
 Figure 4 appears to have two images which overlap. *** ![file] , 
 #1 Usually, I don t reply to posts or emails from anonymous people or people hiding behind a nickname, especially when these concern observations that cast suspicion rather than create clarity, but in this case for the serenity of my co-authors and readers of the article in question, I will be happy to answer. A part of the two images seems to actually overlap, which means that they belong to two fields of view of the microscope of the same sample which is not by chance the control sample. In the experiment in question, the control sample serves to verify the healthy state of the cells, i.e. neurons from stem cells. Once this was verified, the cells were detached from the multiwell and separated in equal dilutions in different wells in triplicate and then inoculated with different nanocomplexes. Actually, the image of the control sample could have been the same because it represented the culture from which all the others were then taken to carry out the dose-response experiments. Having a single initial sample control is common when the biological material is not very available, very expensive or difficult to grow, as in the case considered. In any case, the use of those two figures does not affect in any sense the design of the experiment, nor the validity of the results obtained. Anyone interested in further clarification can write to the corresponding authors. Luca De Stefano, PhD , 
 #2 Dr. De Stefano: Thank you for responding. If I understand correctly, I believe these experiments were performed in triplicate. If that is correct, shouldnu2019t the controls have been executed in the same way and at the same time as the other incubations? Wouldnu2019t there then be 3 sets of control images? , 
 #2 The convoluted method you describe: - does not seem to correspond to what is found in the Materials and Methods of your paper (see image below) - would make the 0 concentration a poor control, as it would be treated differently (manipulation, cell density) to the other concentrations ![file] Moreover, given the  unlimited self-renewal of ES cells, it is not particularly compelling to invoke limited material. What might have made sense would have been for a zero-concentration culture to have been shared without the additional splitting (unless the different nanoparticles had different vehicle), but you don t seem to be describing that either. ,