Development of glycan‑targeted nanoparticles as a novel therapeutic opportunity for gastric cancer treatment

SANTOS, SOFIA N. dosGUSHIKEN JUNIOR, DINO S.PEREIRA, JHONATAS P.M.IADOCICCO, NATALIA M.SILVA, ANDRE H.NASCIMENTO, TATIELLE doDIAS, LUIS A.P.SILVA, FLAVIA R. de O.RICCI-JUNIOR, EDUARDOSANTOS-OLIVEIRA, RALPHBERNARDES, EMERSON S.2023-04-262023-04-262023SANTOS, 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. Development of glycan‑targeted nanoparticles as a novel therapeutic opportunity for gastric cancer treatment. <b>Cancer Nanotechnology</b>, v. 14, n. 1, p. 1-21, 2023. DOI: <a href="https://dx.doi.org/10.1186/s12645-023-00161-2">10.1186/s12645-023-00161-2</a>. Disponível em: http://repositorio.ipen.br/handle/123456789/34015.1868-6958http://repositorio.ipen.br/handle/123456789/34015Chemotherapy 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.1-21openAccessneoplasmsstomachrnaantigenschemotherapyDevelopment of glycan‑targeted nanoparticles as a novel therapeutic opportunity for gastric cancer treatmentArtigo de periódico11410.1186/s12645-023-00161-20000-0002-0029-7313https://orcid.org/0000-0002-0029-731366.776.00