NATALIA MIRANDA IADOCICCO
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Artigo IPEN-doc 29639 Development of glycan‑targeted nanoparticles as a novel therapeutic opportunity for gastric cancer treatment2023 - SANTOS, SOFIA N. dos; GUSHIKEN JUNIOR, DINO S.; PEREIRA, JHONATAS P.M.; IADOCICCO, NATALIA M.; SILVA, ANDRE H.; NASCIMENTO, TATIELLE do; DIAS, LUIS A.P.; SILVA, FLAVIA R. de O.; RICCI-JUNIOR, EDUARDO; SANTOS-OLIVEIRA, RALPH; BERNARDES, EMERSON S.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.