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

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dos Santos, Sofia Nascimento ; Gushiken Junior, Dino Seigo ; Pereira, Jhonatas Pedrosa Marim ; Iadocicco, Natalia Miranda ; Silva, Andre Henrique ; do Nascimento, Tatielle ; Dias, Luis Alberto Pereira ; Silva, Flavia Rodrigues de Oliveira ; Ricci-Junior, Eduardo ; Santos-Oliveira, Ralph ; Bernardes, Emerson Soares

• Document type: Journal article
• Source: CANCER NANOTECHNOLOGY; v. 14, n. 1, p. 21-pg., 2023-12-01.

Abstract

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 (99m)technetium 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. (AU)

• FAPESP's process: 12/06875-6 - Development and production of positron emission tomography radiopharmaceuticals for diagnostic purposes in oncology
• Grantee: Emerson Soares Bernardes
• Support Opportunities: Research Grants - Young Investigators Grants