Gold nanoparticles (AuNPs) have several applications including in medicine. Considering cancer is 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 agent, 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, which 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, is 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 198 AuNPs aiming medical applications since the damage to BSA was found to be proportional to the relative concentration of gold-198.

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Chemotherapy resistance remains a major cause of therapeutic failure in gastric cancer. The combination of genetic material such as interference RNAs (iRNAs) to silence cancer-associated genes with chemotherapeutics has become a novel approach for cancer treatment. However, finding the right target genes and developing non-toxic, highly selective nanocarrier systems remains a challenge. Here we developed a novel sialyl-Tn-targeted polylactic acid—didodecyldimethylammonium bromide nanoparticle (PLA-DDAB) nanoparticles (NPs) loaded with dsRNA targeting ST6GalNac-I and/or galectin-3 genes. Using single photon emission computed tomography (SPECT), we have demonstrated that 99mtechnetium radiolabeled sialyl-Tn-targeted nanoparticles can reach the tumor site and downregulate ST6GalNAc-I and galectin-3 RNA expression levels when injected intravenously. Furthermore, using an in vivo gastric tumor model, these nanoparticles increased the effectiveness of 5-FU in reducing tumor growth. Our findings indicate that cancer-associated glycan-targeted NPs loaded with dsRNA targeting ST6GalNAc-I and/or galectin-3 in combination with standard chemotherapy, have the potential to become a novel therapeutic tool for gastric cancer.

Ao Instituto de Pesquisas Energéticas e Nucleares e, em especial, ao Centro de Radiofarmácia pelo suporte na realização deste trabalho. A Dra. Elaine Bortoletti de Araújo por aceitar a orientação deste trabalho e principalmente pela confiança na sua realização transmitindo todo seu conhecimento, apoio e amizade. A MSc. Jair Mengatti, gerente do Centro de radiofarmácia do IPEN, pelo apoio e a oportunidade de execução deste trabalho. A Dra. Neuza T. O Fukumori e Dra Margareth Mie Matsuda, gerentes do Controle de qualidade pelas facilidades na execução do trabalho. Aos funcionários do Centro de Radioframácia Peterson Squair, Natanael, Antonio Carlos Freire e o bolsista Ricardo pela colaboração na execução dos estudos de imagem realizados neste trabalho. Ao Dr. Carlos Roberto Soares e Dra. Miriam Suzuki do Centro de Biotecnologia do IPEN, pela colaboração no fornecimento das bactérias utilizadas neste trabalho.