B-MRS Newsletter. Year 7, issue 3.


 

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Newsletter of the
Brazilian Materials
Research Society

Year 7, issue 3. April 6, 2020.

B-MRS News

– B-MRS annual event. Due to the uncertainties related to COVID-19, and to prevent putting our community’s health at risk, the Organizing Committee of the event, the Executive Board of B-MRS and IUMRS have decided to postpone the event “XIX B-MRS Meeting + IUMRS ICEM.” More information is at the event’s website: https://www.sbpmat.org.br/19encontro/.

Featured Paper

A Brazilian scientific team developed a molecular machine that stores drugs in internal nanochannels, transports them in a physiological medium and releases them by opening a nanocap only when the acidity of the medium increases, which usually occurs around cancer cells. In in vitro studies, the nanomachine was more effective than the pure drug in eliminating cancer cells. The work was recently reported in the Journal of Materials Chemistry B. Know more.

nanomaquina_news

STI Policies

We interviewed Mariana Mazza, a professional who has worked for more than 3 years monitoring Brazilian government actions with a possible impact on STI and working with parliamentarians to defend scientific research. She told us what her work consists of, the main victories achieved and her next challenges at a time marked by difficulties and uncertainties. See interview.

mariana mazza news

News from B-MRS Members

– Professor Osvaldo Novais de Oliveira Junior (IFSC-USP), former president of B-MRS, signs a text on Brazilian science published in one of the main Brazilian newspapers. Know more.

Materials Research Community

– The first death by Covid-19 in the state of Rio Grande do Norte is professor Luiz Di Souza (UERN).

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XIX B-MRS Meeting + IUMRS ICEM
(Foz do Iguaçu, Brazil,
August 29 – September 2, 2021)

The event is postponed owing to Covid-19.

New date: August 29 to September 2, 2021.

Same venue: Rafain Convention Center – Foz do Iguaçu (Brazil).

Abstract submission: A new schedule will be released.

Event website: www.sbpmat.org.br/19encontro/

Owing to the uncertainties related to the COVID-19, and in order to reduce the risk of hampering the health of our community, the Organizing Committee, the Executive Board of the B-MRS and the IUMRS decided to postpone the 2020 B-MRS and the IUMRS/ICEM meetings.

The conferences are now scheduled to happen from August 29th until September 2nd, 2021, in the city of Iguassu Falls, at the Rafain Convention Center. All participants will be asked to resubmit their abstracts following a new schedule to be released.

Reading Tips

– Researcher at Northeastern University (USA) suggests nanomedicine as an approach for possible treatments of the new coronavirus: nanoparticles the size of the virus that can detect it, adhere to it and make it inactive within the organism. Know more.

– How long does the new coronavirus “live” in different materials? Does the “life” time outside the cells justify its extremely high dissemination? US scientists’ work explained this. Know more.

– Using one of the best supercomputers in the world, scientists are building a model that will show all the atoms in the “shell” of SARS-CoV-2 (the virus causing the Covid-19 pandemic) and the interaction between them. The computational model should help understand in detail how the virus acts in the cells and to develop drugs and vaccines to fight the disease. Know more.

Do you know of any initiative or opportunity in the materials research and innovation community that contributes or could contribute to the fight against Covid-19 in any of its aspects? Share with the community. Write to comunicacao@sbpmat.org.br

Follow us on social media

You can suggest news, opportunities, events or reading tips in the materials field to be covered by B-MRS Newsletter. Write to comunicacao@sbpmat.org.br.

 

 

Featured paper: A molecular machine to fight cancer.


[A reversible, switchable pH-driven quaternary ammonium pillar[5]arene nanogate for mesoporous silica nanoparticles. Santos, ECS ; dos Santos, TC; Fernandes, TS; Jorge, FL; Nascimento, V; Madriaga, VGC ; Cordeiro, PS; Checca, NR; Da Costa, NM; Pinto, LFR; Celia Ronconi. J. Mater. Chem. B, 2020,8, 703-714. https://doi.org/10.1039/C9TB00946A]

A molecular machine to fight cancer

In 2016, the smallest man-made machines ever created, called molecular or nanomachines, gained visibility with the Nobel Prize in Chemistry. These nanometer-sized machines, whose components are molecules that perform controlled movements, could help humanity accomplish complex tasks at the molecular scale.

In the health area, one such task is to effectively fight cancer cells without damaging healthy tissues. It is known that nowadays one of the main problems of the most used therapies concerns the side effects on healthy tissues – a problem that has led many scientists to develop drug delivery systems that can take drugs directly to cancer cells without leaking.

At the Brazilian Federal Fluminense University (UFF), over the last ten years Professor Célia Machado Ronconi and her scientific team have been working on nanomachines for cancer treatment. In her postdoctoral research, carried out between 2003 and 2005, the scientist learned about molecular machines at the University of California, Los Angeles (UCLA), at one of the most qualified laboratories in the world working on this subject – the research group of Sir James Fraser Stoddart, who years later would be awarded the Nobel Prize mentioned at the beginning of this article, alongside with Jean-Pierre Sauvage and Bernard L. Feringa.

In a recently published paper in Journal of Materials Chemistry B, Professor Célia Ronconi, her team and collaborators, all from Brazilian institutions, presented a new nanomachine composed of a drug reservoir and a cap. The machine has an opening/closing lid mechanism that responds to changes in the acidity of the medium in which it is located. When the pH of the medium is similar to that of the blood of a healthy human being (physiological medium), the cap remains closed, preventing the drug from being released. When the pH is more acidic, a characteristic seen around cancer cells, the lid opens and the drug is released. In laboratory in vitro tests, the nanomachine loaded with a well-known chemotherapeutic drug proved to be more effective than the pure drug in eliminating breast cancer cells, destroying 92% of them in 48 hours.

The highlight of this figure shows a zoom of the nanomachine loaded with the drug (green balls). The zoom focuses one of the nanochannels of the closed reservoir and its nanocap, preventing the drug from being released.
The highlight of this figure shows a zoom of the nanomachine loaded with the drug (green balls). The zoom focuses one of the nanochannels of the closed reservoir and its nanocap, preventing the drug from being released.

With these characteristics, the nanomachine developed at UFF shows application potential in the delivery of chemotherapeutic drugs to cancer cells. “The results of this work were extremely promising,” says Professor Ronconi. “However, there is still much to be studied. The next steps of the work will be to test the nanomachine loaded with the drug in other breast cancer cell lines, as only one line (MCF-7) was tested. We will also test the toxicity of the device without the drug in healthy cells and, if the results are positive, in vivo studies will be carried out, using mices genetically altered to have a deficient immune system, ” adds Professor Ronconi.

Assembly and operation of the nanomachine

To achieve the reservoir function, the UFF group synthesized spherical mesoporous silica nanoparticles of about 85 nm in diameter. In addition to being biocompatible, this material has a unique internal honeycomb-like structure, with a set of nanochannels of up to 4 nm in diameter, in which the drug molecules can be stored. The nanoparticles were covered with carboxyl groups (- COOH) that improved the interaction of the reservoir with its cap. For the cap, the researchers chose pilararene, an artificial molecule made up of five aromatic rings, whose first synthesis dates back to 2008 in the scientific literature.

In the assembly and operation of the nanomachine, the electrostatic interactions of attraction controlled by the medium pH were the great allies of the scientific team at UFF. In fact, as confirmed by the researchers in their experiments, in a solution with a pH of 7.4, which represents the acidity of healthy blood, the carboxyl groups (-COOH) that cover the reservoir lose a proton forming carboxylate groups (-COO- ), negatively charged, which interact electrostatically with the positively charged cap. Thus, the electrostatic attraction brings the two parts of the nanomachine together until it prevents the drug from being released. By lowering the pH, that is, by making the solution more acidic, the carboxylate groups (-COO-) gain protons, neutralizing their charge. As a result, the electrostatic attraction between the cap and the reservoir breaks apart, the cap opens and the drug is released.

Functioning of the nanomachine loaded with the drug (pink balls). On the left, at physiological pH, the lids close the reservoir's nanochannels. On the right, the more acidic medium generates the removal of the caps and the drug is released.
Functioning of the nanomachine loaded with the drug (pink balls). On the left, at physiological pH, the lids close the reservoir’s nanochannels. On the right, the more acidic medium generates the removal of the caps and the drug is released.

In the experiments carried out, the UFF group was able to partially release the chemotherapeutic drug (34%) at a pH of 5.5 (probably similar to that surrounding the cancer cells) and almost totally (91%) in a 2.0 acidity medium. All experiments were carried out at a temperature of 37 °C, similar to that of the human body.

History of work

Since 2009, when she became a professor at UFF and set up the Laboratory of Supramolecular Chemistry and Nanotechnology, Professor Célia Ronconi has been working in the different development phases of diverse nanomachines and drug transport and release systems, using chemical, magnetic and luminous stimulants. During Evelyn da Silva Santos’ doctorate, under the guidance of Ronconi, a nanomachine prototype was developed using material available on the market. However, new studies carried out after the defense of her doctorate work, in 2018, showed that the nanoparticles used as reservoirs formed clusters in the physiological environment (the solution that emulates blood in experiments). Thus, Professor Ronconi involved postdoctoral fellow Thiago Custódio dos Santos and doctoral student Tamires Soares Fernandes in the development of new material. “They continued the project and synthesized a material with excellent dispersion in the physiological environment, and the device was redone, as well as the drug release studies,” says professor Ronconi. The biological tests of the nanomachine were performed at INCA’s molecular carcinogenesis group, by researchers Luis Felipe Ribeiro Pinto and Nathália Meireles da Costa, and the technician Fernanda Jorge. The study also included the participation of the Brazilian Center for Research in Physics (CBPF) in the characterization of materials by microscopy techniques, carried out at the Multi-User Laboratory for Nanoscience and Nanotechnology (LABNANO). The research received funding from the Brazilian agencies CNPq, CAPES and FAPERJ.

Main authors. From the left: Evelyn Santos, Thiago Custódio, Tamires Soares and Célia M. Ronconi.
Main authors. From the left: Evelyn Santos, Thiago Custódio, Tamires Soares and Célia M. Ronconi.