Featured paper: Nanoclays to overcome toxicity.

[Paper: Reaching Biocompatibility with Nanoclays: Eliminating the Cytotoxicity of Ir(III) Complexes. Malte C. Grüner, Kassio P. S. Zanoni, Camila F. Borgognoni, Cristiane C. Melo, Valtencir Zucolotto, and Andrea S. S. de CamargoACS Applied Materials & Interfaces 2018 10 (32), 26830-26834DOI: 10.1021/acsami.8b10842.]

Nanoclays to overcome toxicity

Working in laboratories of the São Carlos Institute of Physics (IFSC – USP), a scientific team developed a strategy that eliminates the cytotoxicity (ability to destroy cells) of a group of compounds with very interesting photophysical properties for health applications . The study made viable the use of these substances, once toxic, in the study of living organisms and in the diagnosis and treatment of diseases. In addition to eliminating cytotoxicity, the strategy modifies some properties of compounds by adding new functions that can be harnessed for intracellular oxygen sensing and to improve the efficiency of luminescent devices such as OLEDs.

The work was reported in an article recently published in the journal ACS Applied Materials and Interfaces (impact factor 8,097).

It all started in an informal conversation between three postdoctoral fellows linked to IFSC-USP laboratories: Malte C. Grüner and Kassio P. S. Zanoni, both linked to the Laboratory of Functional Materials Spectroscopy (LEMAF), and Camila F. Borgognoni of the Group of Nanomedicine and Nanotoxicology (Gnano). Zanoni had worked with iridium (III) complexes during his doctorate, and wanted to take advantage of some properties of these compounds to use them as photodynamic therapy agents. Such therapy refers to a set of treatments for diseased tissues, such as those affected by cancer, in which an external radiation source is used for the activation at the appropriate time of a compound inserted into the body, which is responsible to destroy the cells that need to be eliminated.

The post-doc Zanoni’s desire, however, came up against the high cytotoxicity of iridium (III) complexes. The postdoc Grüner then had the innovative idea of trying to use laponites (materials he had studied in his doctorate) to inhibit the cytotoxicity of the compounds. From this idea, Grüner and Zanoni carried out the preparation and characterization of the materials in LEMAF, coordinated by Prof. Andrea S. S. de Camargo. At GNano, coordinated by Prof. Valtencir Zucolotto, the post-doc Borgognoni and the student Cristiane Melo were in charge to investigate the interactions of the nanoparticles with the cells.

The authors of the paper. From the left: Kassio Zanoni, Camila Borgognoni, Malte Grüner, Cristiane Melo, Valtencir Zucolotto, and Andrea de Camargo.
The authors of the paper. From the left: Kassio Zanoni, Camila Borgognoni, Malte Grüner, Cristiane Melo, Valtencir Zucolotto, and Andrea de Camargo.

Strategy and applications

Illustration of the adsorption of Ir (III) complexes (blue spheres) on the surface of laponite nanodisks (yellow disks), in solution.
Illustration of the adsorption of Ir (III) complexes (blue spheres) on the surface of laponite nanodisks (yellow disks), in solution.

One of the main properties of iridium (III) complexes is their intense luminescence (emission of light not resulting from heat) in a wide range of colors. This feature may be useful for illuminating cells within living organisms in bioimaging techniques, used for both research and for diagnosis and treatment of diseases.

In turn, laponites, which are synthetic nanoclays fully compatible with living tissues, have often been proposed in the scientific literature as nanoplataforms for transporting drugs and other compounds within living organisms. The laponites are about 25 nm in length and only 1 nm in height.

In the work of the IFSC-USP team, a new material was developed as a result of the adsorption of iridium (III) complex molecules on the surface of laponite nanodiscs.

The researchers found in the laboratory (in vitro) the ability of the new material to be absorbed by cells, its luminescence within cells and its low citotoxicity. For this, they used liver cells and observed their interaction with the new nanomaterial, comparing it with the interaction with the pure iridium (III) complex. The results were highly favorable to iridium (III) laponite nanodiscs, which proved to be harmless to the cells, besides presenting good penetration and high luminescence – characteristics that make them very suitable for application in bioimaging techniques.

Light emission in various colors of the developed nanomaterials (Ir (III) complexes adsorbed on laponite) distributed in xerogels (upper part) and in liver tissue cells (lower part).
Light emission in various colors of the developed nanomaterials (Ir (III) complexes adsorbed on laponite) distributed in xerogels (upper part) and in liver tissue cells (lower part).

“In this work, it was demonstrated for the first time that the adsorption of iridium (III) complexes (in general, highly toxic) on the surface of laponite nanodisks is capable to completely extinguish the cytotoxicity of these compounds “, summarizes the post-doc Kassio Zanoni , who in 2017 was the winner of B-MRS Young Researcher Award. “This makes it highly feasible to use previously toxic compounds in cell media without impairing the integrity of the medium and therefore has the potential to expand the research of new biocompatible materials for use in cell mapping, theranostics and photodynamic therapy”, he adds.

According to the authors, the new nanomaterial could act as a photodynamic therapy drug, since, when irradiated with certain types of radiation, it produces a molecule (the singlet oxygen) that acts in the destruction of cancer cells. In this way, the nanomaterial also becomes promising in the field of theranostics, which proposes the combination, on the same platform, of the diagnosis of diseases by bioimaging with its cure through photodynamic therapies.

In addition, the nanomaterial can be used as a sensor to accurately determine the amount of oxygen distributed inside a cell. “As demonstrated in our work, the emission intensity of this nanomaterial is a variable as a function of the concentration of oxygen”, justifies Zanoni.

Finally, the nanomaterial, in the form of a thin nanometric film, could also be applied to organic light-emitting diodes (OLEDs) – devices that are already used, for example, in cellular screens. “This is because the iridium (III) complex adsorbed on laponite aggregates photophysical, photochemical and electrochemical properties that are strategic for the development of more efficient devices”, explains Zanoni.

This research was carried out with funding from The São Paulo Research Foundation (FAPESP).

Featured scientist: interview with Prof. Oscar Manoel Loureiro Malta.

DSC_4269CMYK-Photo 1Brazil, besides having one of the world’s largest reserves of ores with lanthanide elements, also occupies a prominent place in the research of these elements and their compounds, which have significant applicability in strategic areas such as energy, health and catalysis, as well as in many other areas.

One of the most prominent Brazilian scientists in this research field is Oscar Manoel Loureiro Malta, born in the city of Recife (state of Pernambuco) 63 years ago. Malta is Professor at the Department of Fundamental Chemistry of the Federal University of Pernambuco (UFPE). Over the course of four decades, he has made important contributions to the research on lanthanides, both in the fundamental and applied fields.

Malta defined his interest in science during his high school years. In 1974, he started the Chemical Engineering course at UFPE and the Physics course at the Catholic University of Pernambuco. After completing his degree in Physics, he left the Chemistry course to join the Master’s degree in Physics at UFPE. There he carried out research work on spectroscopy of lanthanide compounds, mentored by Professor Gilberto Fernandes de Sá. In December of 1977, he obtained the master’s degree. He continued his studies on lanthanide spectroscopy in his doctorate at the University of Paris VI (France), also known as Pierre et Marie Curie Université, guided by Professor Yves Jeannin. He obtained his doctorate in March 1981. He then returned to Recife, where that same year he became professor at UFPE. In 1986, he returned to France for one year as a visiting researcher in the group of Paul Caro, a world-renowned scientist in the lanthanide area, linked to the French National Center for Scientific Research (CNRS).

Oscar Malta was visiting professor in several international institutions: University of Wroclaw (Poland) in 2015; University of Aveiro (Portugal) in 2005; Industrial University of Santander (Colombia) in 2000; University of São Paulo, USP, in 1995, 1996 and 1999, and Paulista State University Júlio de Mesquita Neto, UNESP, in 1994-95 and 1998.

At UFPE, he participated in the creation and consolidation of the Department of Fundamental Chemistry, where he served as department head (1987-89) and postgraduate coordinator (1991-93 and 1999-2001). He was also the coordinator of two national research networks: the National Network of Molecular Nanotechnology and Interfaces, RENAMI (2001 – 2009), and the National Institute of Science and Technology for Integrated Markers, INAMI (2009-2015).

Malta has received a number of acknowledgments for his scientific trajectory. On November 15, 2017, he received an honorary doctorate from the University of Wroctaw, an important institution in Poland where nine Nobel laureates have emerged. In 2016, a special edition of the Journal of Luminescence (publisher Elsevier) on lanthanide spectroscopy was dedicated to this researcher from Pernambuco (https://doi.org/10.1016/j.jlumin.2015.11.024). In 2015, Malta received the Ricardo Ferreira Award for Scientific Merit, recently created by the Foundation for Science and Technology of Pernambuco, Facepe. In 2014, he received the Professor Paulo José Duarte Medal from the Brazilian Chemistry Association. In 2003, he became a full member of the Brazilian Academy of Sciences, ABC.

In this year, Malta was chairman of the International Conference on Luminescence (ICL), which, after seventeen editions in the northern hemisphere, was held in the Brazilian city of João Pessoa.

With a productivity research grant 1A of CNPq, Oscar Malta is the author of approximately 180 papers published in international journals, with about 7,000 citations in the Web of Science. The scientist has a 42 H index.

Here is our interview with Oscar Manoel Loureiro Malta.

SBPMat newsletter: What do you believe are your main contributions to the Materials area and why do you consider them more relevant?

Oscar Malta:  Since my master’s degree, which I started in 1977, my work has been in the areas of theoretical chemistry, binding field theory, 4f-4f spectral intensities, non-radioactive energy transfer, in particular intramolecular energy transfer in coordination compounds with lanthanide ions whose theory I developed between 1996 and 1998 and which until today I continue working on, as well as several groups in Brazil and abroad. Over the last three decades, in a work that involves great and extraordinary synergy between theory and experiment, we have been able to construct a very successful scheme for the modeling of highly functional luminescent lanthanide ion coordination compounds with the potential for diverse applications such as luminescent markers in bioassays. Many of these results were obtained during the time I coordinated two national nanotechnology networks. The first, National Network of Molecular Nanotechnology and Interfaces (RENAMI), was in force from 2001 to 2009, the second, the National Institute of Science and Technology for Integrated Markers (inct-INAMI), was in force from 2009 to 2015. Coupled to these results two important themes were also developed: the effect of metal nanoparticle plasmas on the luminescence of compounds with lanthanide ions, a subject that is currently linked to the so-called plasmon, and the concept of polarizability of the coating region in the chemical bond as a way to quantify covalence, which I introduced between 2002 and 2005 in order to better understand the chemical bond involving 4f orbitals. This concept was subsequently generalized to any chemical bonding, from single molecules to complex materials. In all these results it is important to emphasize the students’ participation, from scientific initiation to the doctorate.

SBPMat Bulletin:  You started researching in the field of lanthanide ion compounds spectroscopy in your master’s degree, 40 years ago, and you’re still working in the area. What most appeals to you in this research topic? Is it still a promising area? What has changed in the research in this area in Brazil since the 1970s so far?

Oscar Malta:  Lanthanides and their compounds are fascinating. They took me into the world of theoretical chemistry, in the world of angular momentum algebra, in the world of the interaction of radiation with matter, and into the world of spectroscopy. When I finished my master’s degree, everything was in place for me to go on to do a doctorate in England to work in atomic physics. At that time he was in Recife, at the invitation of Gilberto Sá and Ricardo Ferreira, Paul Caro, one of the most renowned researchers in lanthanide spectroscopy. He presented a seminar that really impressed me. I gave up on going to England and went to work for Paul Caro’s group at CNRS in Meudon-Bellevue in France. At first the plan was to develop an experimental thesis. However, I wanted to work on the theory. Paul Caro accepted this without problems, and a very fruitful theory/experiment interaction emerged that extended to other groups and continues to this day, always with much to do from a fundamental point of view and from the point of view of applications. Brazil is one of the world leaders in this field, with extremely active and internationally recognized research groups in the country. In fact there is again a discussion about the production of lanthanides since Brazil is a country rich with the minerals of these elements, so important for today’s technology and undoubtedly for the future. We cannot overlook this.

SBPMat Bulletin: Now we invite you to leave a message for the readers who are starting their scientific careers.

Oscar Malta:  There is now a strong tendency of young researchers (I am referring to the scientific area under consideration here) to exacerbate the value of applied science in a short-sighted manner. As a result they forget the theoretical foundations and they often do not know the history of the subject, even the experimental history, that they work with or intend to work with. It is exhausting (a fact) to notice this in scientific meetings and I usually am amazed. This is like a linear inflationary process in which money is thrown into the market without having a stabilizer. Sooner or later it ends up in trouble, problems whose creative solutions (an assumption that must accompany a scientist) could be found if greater investment had been deposited in the theoretical foundation and greater attention given to the history of the situation at hand. Therefore, with respect to this question, my message is: do not neglect good theoretical formation and the knowledge of the origin of the subject with which you intend to work. Countries that are now developing and exporting good technology realize how important this is.

SBPMat Bulletin: Feel free to share other comments with our community.

Oscar Malta: Science and technology are more than ever a social activity that requires creativity (as always), training, and therefore education, dedication and strong interdisciplinary cooperation. And it requires investments. Without these ingredients, coupled with sound and sensible ethics committees, we will not be able to create intelligent and reliable science and technology policies that will ensure the continuation of human civilization. The great astronomer Carl Sagan said that not taking these ingredients seriously and the notion that five billion years from now our solar system will have been burned (by our red giant), we will have no chance of getting out of here. This sounds like science fiction, but it’s not. Hopefully the next generations, especially our leaders, will realize this. But I am optimistic in this regard, like a great neuroscientist (Miguel Nicolelis) who wrote “Beyond Boundaries”, which I recommend to my colleagues in Materials Science – especially with respect to emerging properties.

Featured paper: Revealing secrets of the luminescence of a lanthanide ion.

Paper: Mechanisms of optical losses inthe 5D4 and 5D3 levels in Tb3+ doped low silica calcium aluminosilicate glasses. J. F. M. dos Santos, I. A. A. Terra, N. G. C. Astrath, F. B. Guimarães, M. L. Baesso, L. A. O. Nunes and T. Catunda. J. Appl. Phys. 117, 053102 (2015). DOI: 10.1063/1.4906781.

A team of scientists from Brazilian institutions has expanded the comprehension of the mechanisms that restrict the light emission efficiency in materials doped with trivalent terbium ion (Tb³+). This ion, found in the rare earth group, subgroup of lanthanides, displays luminescent emissions from ultraviolet to infrared. Its intense green emission, with approximately 545 nm of wave length, is particularly interesting for technological purposes.

Some years ago, for instance, Japanese researchers produced laser emissions with Tb3+ doped optical fibers. However, their device displayed low efficiency, due to the saturation of its optical gain, even at low excitation levels.

Luminescence process of a Tb³ doped LSCAS sample, excited by a blue laser, emitting green light. The pictures portray the sample in a state of (a) non-excitation and (b) excitation.

Taking up this technological issue, the team of Brazilian scientists has conducted a thorough study on the processes that cause the saturation of the green emission. For that, they used Tb3+ to dope a material which, thanks to its properties, ensures high efficiency to the emission, mainly in infrared: the low silica calcium aluminosilicate glass, also known as LSCAS.

The study involved two research groups that have been collaborating for approximately two decades, the group of spectroscopy of solids from the São Carlos Institute of Physics at the São Paulo University (USP), and the photothermics group from State University of Maringá (UEM). The results were reported in a paper that appeared recently on the Journal of Applied Physics.

Firstly, glass samples with different dopant concentrations were prepared by the UEM group.

Picture of the LSCAS samples. The base sample has a Tb3+ concentration of 0.05%.

At IFSC-USP, the samples were excited using a laser at two different wavelengths, 488 nm (visible) and 325 nm (ultraviolet), and their absorption, emission and excitation spectra were obtained. Analyzing them, the scientists from the group of spectroscopy of solids observed certain particularities in the behavior of some luminescent emissions, such as a strong saturation in a green emission, similar to the one found in the laser presented by the Japanese scientists. In other wavelengths, they noted, for example, a decrease in luminescence occurring at lower excitation levels than expected. Thus, the researchers managed to conclude that the mechanism associated in the literature to the emissions from Tb3+ doped materials, also known as cross relaxation, was not enough to completely explain the behavior of the emissions or even the saturation of the green emissions, and proposed the additional action of other processes.

“Additional loss mechanisms, such as emissions by defects in the matrix, energy upconversion processes, to name a few, have a significant influence in the system we have studied”, explains Tomaz Catunda, professor at USP and corresponding author of the article. “These decay paths, previously ignored by the literature, are very important in the manufacturing of optical devices with Tb3+ doped materials”, he adds.

The study of Tb³+ doped glasses by the Brazilian team started during the Doctoral dissertation of Idelma Terra, defended in 2013 at USP, which aimed to develop materials in order to increase the efficiency of solar cells. Her work was granted the 2014 “Vale-Capes Science and Sustainability Award”. The study of these materials continued in Giselly Bianchi’s Doctoral dissertation, performed at UEM, and in the Master’s thesis of Jéssica Fabiana Mariano dos Santos, defended in 2014 at EESC-USP.

The article published on the Journal of Applied Physics has joined dozens of papers born from the collaboration between the groups of spectroscopy of solids and photothermics, in some cases also involving other scientists from Brazil and abroad, focused on the optical spectroscopy of calcium aluminate glasses doped with rare earth ions and their applications in light-emitting devices.