Hyaluronic acid-coated niosomal sorafenib targets CD44 and suppresses NFκB signalling in oral squamous cell carcinoma.

OBJECTIVES

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 CD44-targeted delivery to OSCC cells.

MATERIALS AND

METHODS

SOR@Nio/HA displayed a mean hydrodynamic diameter of 177±8 nm (PDI=0.23-0.26) and high encapsulation efficiency (86.34%), with pH-responsive release (45% at pH=5.5 and 30% at pH=7.4, in 24 hr).

RESULTS

In CAL27 cells, SOR@Nio/HA significantly enhanced cytotoxicity versus free sorafenib, lowering IC50 from 11.8±1.1 µM to 5.2±0.9 µM (P<0.01), and increased Annexin V/PI-defined apoptosis relative to controls. qRT-PCR showed suppression of NF-κB targets, with COX-2 and MMP-9 reduced to 0.35-fold and 0.32-fold of the control, respectively, alongside a pro-apoptotic shift in the BAX/BCL-2 axis.

CONCLUSION

Collectively, these data indicate that SOR@Nio/HA improves intracellular delivery and potentiates sorafenib's antitumor activity by CD44-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.