Fucoidan-functionalized liposomal nanocarriers for targeted miR-217-5p delivery and combined antitumor treatment in pancreatic ductal adenocarcinoma

The clinical translation of microRNA (miRNA) therapy is hindered by poor tumor specificity and inefficient delivery. In this study, we constructed a targeted nanoplatform using marine sulfated polysaccharide fucoidan (FU) to encapsulate miR-217-5p in FU-modified cationic liposomes (FU-LIP-miR) for the treatment of pancreatic ductal adenocarcinoma (PDAC), alone or in combination with gemcitabine (GEM). In this system, FU serves primarily as a targeting ligand. FU was incorporated as a functional surface ligand. Previous studies have demonstrated a high-affinity interaction between FU and P-selectin, suggesting that this interaction may contribute to the enhanced tumor-associated accumulation of FU-functionalized nanocarriers. Furthermore, FU is susceptible to degradation by H 2 O 2 within the tumor microenvironment, consequently enabling controlled drug release. Initial findings confirmed that that miR-217-5p was significantly downregulated in PDAC tissues. FU-LIP-miR promoted the tumor accumulation and delivery of miR-217-5p and restored its expression, which was accompanied by reduced PDAC cell proliferation, migration, and invasion. Notably, FU can also be employed as an active targeting ligand. FU-LIP-miR combined with GEM produced an enhanced antitumor effect and increased apoptosis in PDAC cells. In a subcutaneous xenograft model using Panc02 cells in C57BL/6 mice, the combination of FU-LIP-miR and GEM produced enhanced antitumor efficacy compared with the corresponding control treatments. This study underscores the pivotal role of FU as a versatile polysaccharide in the design of targeted delivery platforms, thereby providing a novel and promising noncoding RNA-based therapeutic approach for PDAC using polysaccharide materials.

Abstract from PubMed (PMID 42956982). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.