Hyaluronic acid-coated niosomal sorafenib targets CD44 and suppresses NF‑κB signalling in oral squamous cell carcinoma

Articles in Press

Document Type : Original Article

Authors

1 Department of Stomatology, Shungeng Campus, Jinan Stomatological Hospital, No.73, Shungeng Road, Shizhong District, Jinan, Shandong, 250001, China

2 Department of Stomatology, Central Hospital affiliated to Shandong First Medical University, No.105, Jiefang Road, Lixia District, Jinan, Shandong, 250013, China

3 Department of Stomatology, Shandong Medical College, No 5460, Second Ring South Road, Jinan, Shandong, 250002, China

10.22038/ijbms.2026.88283.19066

Abstract

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 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.

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References

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Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 02 May 2026

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