Injectable thermosensitive hydrogel-encapsulated paclitaxel liposomes enriched with miR-455-3p antagomir for dormancy therapy of salivary adenoid cystic carcinoma

Abstract

Postoperative salivary adenoid cystic carcinoma (SACC) without symptoms is marked by dormant tumor cells in the primary site and metastatic organs. These cells, when reactivated, cause recurrence and metastasis. A treatment strategy that targets the “awakening” and elimination of these cells, combined with chemotherapy, could prevent and treat recurrence and metastasis. High expression of miR-455-3p were found to be crucial for SACC cell dormancy induced by serum starvation. High expression of miR-455-3p was inversely correlated with Ki-67 levels, while its reduction was linked to SACC tumor recurrence. These findings further imply that elevated miR-455-3p expression in SACC is indicative of a state of tumor dormancy. Mechanistically, a dual luciferase reporter assay provided further validation that miR-455-3p targeted GNPNAT1, regulating SACC dormancy. GNPNAT1 is downregulated in SACC tissues, and its overexpression inhibits cell dormancy and migration/invasion. An injectable, thermosensitive hydrogel designed to deliver antagomiR-455-3p via paclitaxel liposomes formed a Lip@miR hydrogel. This hydrogel “awakened” dormant SACC cells, suppressing their tumorigenic potential and leading to their eradication through sustained paclitaxel release in vivo. This approach presents a new therapeutic strategy for eliminating dormant tumor cells and reducing the risk of post-therapy cancer relapse.