Hyaluronic acid-coated niosomal sorafenib targets CD۴۴ and suppresses NF‑κB signalling in oral squamous cell carcinoma

Objective(s): Oral squamous cell carcinoma (OSCC) remains highly lethal and is driven, in part, by chronic NF-κB-mediated inflammation. Sorafenib, a multikinase inhibitor of RAF/VEGFR/PDGFR, can suppress these pathways, but its clinical utility is limited by hydrophobicity, toxicity, and poor tumor penetration. We engineered hyaluronic acid-coated niosomes encapsulating sorafenib (SOR@Nio/HA) to enable CD۴۴-targeted delivery to OSCC cells.Materials and Methods: SOR@Nio/HA displayed a mean hydrodynamic diameter of ۱۷۷±۸ nm (PDI=۰.۲۳-۰.۲۶) and high encapsulation efficiency (۸۶.۳۴%), with pH-responsive release (۴۵% at pH=۵.۵ and ۳۰% at pH=۷.۴, in ۲۴ hr).Results: In CAL۲۷ cells, SOR@Nio/HA significantly enhanced cytotoxicity versus free sorafenib, lowering IC۵۰ from ۱۱.۸±۱.۱ µM to ۵.۲±۰.۹ µM (P<۰.۰۱), and increased Annexin V/PI-defined apoptosis relative to controls. qRT-PCR showed suppression of NF-κB targets, with COX-۲ and MMP-۹ reduced to ۰.۳۵-fold and ۰.۳۲-fold of the control, respectively, alongside a pro-apoptotic shift in the BAX/BCL-۲ axis.Conclusion: Collectively, these data indicate that SOR@Nio/HA improves intracellular delivery and potentiates sorafenib’s antitumor activity by CD۴۴-mediated uptake and inhibition of NF-κB-driven inflammatory and invasive programs. HA-guided niosomal sorafenib warrants in vivo validation as a selective nanotherapeutic strategy for OSCC.

کلیدواژه ها:

Carcinoma ، CD۴۴ ، Drug delivery systems ، Hyaluronic acid ، Mouth neoplasms NF-kappa B ، Sorafenib ، Squamous Cell