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

Autor: Sofia Nascimento dos Santos, Dino Seigo Gushiken Junior, Jhonatas Pedrosa Marim Pereira, Natália Miranda Iadocicco, André Henrique Silva, Tatielle do Nascimento, Luís Alberto Pereira Dias, Flávia Rodrigues de Oliveira Silva, Eduardo Ricci-Junior, Ralph Santos-Oliveira, Emerson Soares Bernardes
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cancer Nanotechnology, Vol 14, Iss 1, Pp 1-21 (2023)
Druh dokumentu: article
ISSN: 1868-6958
1868-6966
DOI: 10.1186/s12645-023-00161-2
Popis: 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 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.
Databáze: Directory of Open Access Journals
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