Development of glycan-targeted nanoparticles as a novel therapeutic opportunity for gastric cancer treatment
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.
Citação
@online{santos,_sofia_nascimento2023,
author = {Santos, Sofia Nascimento, Dos and Dino Seigo Gushiken ,
Junior and Jhonatas Pedrosa Marim , Pereira and Natália Miranda ,
Iadocicco and André Henrique , Silva and Nascimento, Tatielle, Do
and Luís Alberto Pereira , Dias and Oliveira Silva, Flávia
Rodrigues, De and Eduardo , Ricci-Junior and Ralph , Santos-Oliveira
and Emerson Soares , Bernardes},
title = {Development of glycan-targeted nanoparticles as a novel
therapeutic opportunity for gastric cancer treatment},
volume = {14},
number = {1},
date = {2023-12-01},
doi = {10.1186/s12645-023-00161-2},
langid = {pt-BR},
abstract = {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.}
}