Aptamer-functionalized exosomes co-delivering miR-934 inhibitor and gemcitabine for targeted pancreatic cancer therapy

Pancreatic cancer remains a malignancy with limited treatment efficacy and high resistance to chemotherapy. miR-934 was identified as an oncogenic miRNA significantly upregulated in pancreatic cancer, promoting tumor progression, epithelial-mesenchymal transition (EMT), and chemoresistance by targeting the tumor suppressor PRUNE2. Inhibition of miR-934 sensitized cancer cells to Gemcitabine (GEM)-induced apoptosis, highlighting its therapeutic potential. To enhance delivery efficiency, AS1411 (oligonucleotide aptamer of nucleolin)-functionalized exosomes were engineered to co-deliver miR-934 inhibitor and GEM. The functionalized exosomes demonstrated high encapsulation efficiency, enhanced cellular uptake and tumor-targeting capability, and improved suppression of malignant phenotypes. This platform not only suppressed cell migration, invasion, and EMT but also enhanced GEM-induced apoptosis by restoring PRUNE2 expression and activating pro-apoptotic pathways. Furthermore, PRUNE2 overexpression reversed the malignant phenotypes and gemcitabine resistance induced by miR-934, further confirming the critical role of the miR-934/PRUNE2 axis in pancreatic cancer progression. In vivo, AS1411-functionalized engineered exosomes co-delivering miR-934 inhibitor and gemcitabine exhibited enhanced tumor accumulation and significantly suppressed tumor growth compared with free drug treatment and non-functionalized exosomes. These findings underscore the potential of aptamer-functionalized exosomes as a targeted therapeutic strategy for pancreatic cancer by integrating miRNA modulation and chemotherapeutic delivery.

Abstract from PubMed (PMID 43010059). 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.