JONNATAN JULIVAL DOS SANTOS
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Artigo IPEN-doc 24857 Bovine serum albumin conjugated gold-198 nanoparticles as model to evaluate the damage caused by ionizing radiation to biomolecules2018 - SANTOS, JONNATAN J.; LEAL, JESSICA; DIAS, LUIS A.P.; TOMA, SERGIO H.; CORIO, PAOLA; GENEZINI, FREDERICO A.; KATTI, KATTESH V.; ARAKI, KOITI; LUGAO, ADEMAR B.Gold nanoparticles (AuNPs) have several applications including in medicine. Considering cancer as one of the most common diseases for men and women, new treatments and more specific and effective drugs, which cause less side effects, have been actively pursued. Among them, gold-198 can be engineered as theranostic agents, working as contrast (exploiting gamma emission) and treatment agents (beta emission). Accordingly, a new procedure for the production of 14 nm diameter radioactive citrate protected gold-198 nanoparticles, that were then conjugated with bovine serum albumin utilizing 3-mercaptopropionic acid directly bound to AuNPs surface as anchoring groups, generating fully dispersible nanoparticles in aqueous media, are described. The effect of gamma and beta radiation on grafted BSA was evaluated by direct irradiation of the corresponding cold material and comparing with the damage caused on BSA grafted gold-198 nanoparticles prepared from a neutron activated gold foil. The investigation by fluorescence and Raman spectroscopy indicated that the damage to BSA chromophore groups is proportional to the dose (from 0.1 to 1 kGy) and that chromophores groups close to the particle surface are more prone to damage. Gold-198 nanoparticles conjugated with bovine serum albumin showed that process is much more localized next to nanoparticles surface since each gold core acts as a punctual radiation source. In short, AuNPs can enhance the damage caused by irradiation of cold nanoparticles and AuNPs@MPA-BSA is a suitable model to probe the effect of gamma and beta emitter on biomolecules. Furthermore, the strategy of diluting the gold-198 with cold gold atoms was shown to be suitable to control the activity of 198AuNPs aiming medical applications, since the damage to BSA was found to be proportional to the relative concentration of gold-198.Resumo IPEN-doc 24847 Synthesis of high stable gold (198) nanoparticles for radiotherapy2017 - SANTOS, JONNATAN J.; LEAL, JESSICA; DIAS, LUIS A.P.; TOMA, SERGIO H.; CORIO, PAOLA; ARAKI, KOITI; GENEZINI, FREDERICO A.; KATTI, KATTESH V.; LUGAO, ADEMAR B.Cancer has become a problem in the last years, is expect be diagnosed more than 500 000 new cases in 2017, only in Brazil, according to Brazilian Cancer Nacional Institute. Among women breast cancer is the most common and among men the most representative is prostate cancer, and although treatments for both cancers have been already developed, new methods more efficient and that causes less damage to the patient are always being searched. Gold nanoparticles (AuNps) have many different applications on chemistry, biology, medicine, etc; their low reactivity and toxicity and high stability become it very interesting for bioapplications, such as drugs delivery and biosensing. In this work, we had developed a new method to prepare 198AuNps, from a leaf of gold bombed by neutrons, adapting Turkevich method, these nanoparticles were modified with bovine serum albumin (BSA) and characterized by multiple techniques, after 30 days (eleven half-life decays). This methodology was capable of generate AuNps with almost 14 nm and Zeta potential higher than -37 mV, very stable. BSA can be used for different applications, like a simple stabilizer or to increase cellular uptaking, but in our case its chromophore groups were utilized to follow damages caused by radiation, as a sensor for radiation damage, a dosimeter. Bellow are presented TEM image, Zeta potential measures and fluorescence spectroscopy of the 198AuNps-BSA samples.Resumo IPEN-doc 24835 Radiation-induced "one pot" synthesis for cell therapies2017 - LUGAO, ADEMAR B.; FAZOLIN, GABRIELA N.; VARCA, GUSTAVO H.C.; SANTOS, JORGE G.; BARROS, JANAINA; FUCASE, TAMARA; SANTOS, JONNATAN J.; LEAL, JESSICA; GRASSELLI, MARIANO; KATTI, KATTESH V.The dream of Marie Curie lab’s expressed by Regaud and Lacassagne in 1927 was to administer radiations with penetration range of molecular dimensions to the organism and selectively fixed in the protoplasm of cells one seeks to destroy. Gold nanoparticles can be employed as a radiation sensitizer by utilizing mainly Auger effect and photoelectrons. Auger electrons are released in large numbers with low kinetic energy therefore these electrons damage cells over a very short range: less than the size of a single cell, on the order of nanometers. Gold-198 is a beta and gamma emitter can be employed for therapy as well as diagnostic. The radioactive properties of gold include: Au (βmax=0.96 MeV; t1/2 = 2.7 days) and Au (βmax =0.46 MeV; t1/2 = 3.14 days), making it a strong candidate for theranostics. However, Gold or Gold-198 need to internalize selectively in tumor cells. Conjugation with proteins and peptides can make them very selective. While radioactive nanoparticles can offer a much higher dose payload than ions for therapy and diagnostic, in addition to the huge surface to bind targeting species presented by the nanoparticles, functionalization with proteins may potentially increases the particle uptake by tumors or tissues. Albumin and Papain features a set of characteristics that assure applications as natural drug carriers with particular attractive properties in oncology. Albumin may be easily crosslinked and engineered towards loading of large number of hydrophobic molecules as well as hydrophilic ones. They can be bound in a reversible way and the delivery controlled by endogenous mechanism. Alternatively to conventional systems, albumin can be crosslinked by radiation in such way that dialdehydes or toxic chemicals are totally avoided . Conjugation of such materials with sugars, peptides, antibodies, proteins among others is routinely used nowadays for targeting. The main purpose of this work was the development of one pot in situ synthesis of radioactive gold 198 nanoparticle encapsulated by albumin for application in cancer Theranostics. While crosslinked albumin may provide a nontoxic coating on AuNPs with a controllable hydrodynamic diameter, conventional AuNP can be activated by nuclear reactor to produce AuNP. The gamma or beta radiation originated from the gold nanoparticle was used to crosslink the Albumin layer. The use of a radioactive particle able to emit radiation for crosslinking of the Albumin layer and simultaneous theranostic application was tried for the first time. The elegant procedure and simplicity of the production process combined with the properties of Au and the safety of AuNP/BSA make this new particle an exciting advancement in cancer therapy and diagnosis. Gold conjugated protein nanoparticles and protein nanoparticles itself were also produced in an radiation induced one pot process. Crosslinking and protein damage werea cessed by different techniques.