Purpose: Over the past 30 years, no consistent survival benefits have been recorded for
anticancer agents of advanced hepatocellular carcinoma (HCC), except for the multikinase
inhibitor sorafenib (Nexavar®), which clinically achieves only ~3 months overall survival
benefit. This modest benefit is attributed to limited aqueous solubility, slow dissolution rate
and, consequently, limited absorption from the gastrointestinal tract. Thus, novel formulation
modalities are in demand to improve the bioavailability of the drug to attack HCC in a more
efficient manner. In the current study, we aimed to design a novel sorafenib-loaded carbon
nanotubes (CNTs) formula that is able to improve the therapeutic efficacy of carried cargo
against HCC and subsequently investigate the antitumour activity of this formula.
Materials and methods: Sorafenib was loaded on functionalized CNTs through physical
adsorption, and an alginate-based method was subsequently applied to microcapsulate the
drug-loaded CNTs (CNTs-SFN). The therapeutic efficacy of the new formula was estimated
and compared to that of conventional sorafenib, both in vitro (against HepG2 cells) and in
vivo (in a DENA-induced HCC rat model).
Results: The in vitro MTT anti-proliferative assay revealed that the drug-loaded CNTs
formula was at least two-fold more cytotoxic towards HepG2 cells than was sorafenib itself.
Moreover, the in vivo animal experiments proved that our innovative formula was superior to
conventional sorafenib at all assessed end points. Circulating AFP-L3% was significantly
decreased in the CNTs-SFN-MCs-treated group (14.0%) in comparison to that of the DENA
(40.3%) and sorafenib (38.8%) groups. This superiority was further confirmed by Western
blot analysis and immunofluorescence assessment of some HCC-relevant biomarkers.
Conclusion: Our results firmly suggest the distinctive cancer-suppressive nature of CNTs-
SFN-MCs, both against HepG2 cells in vitro and in a DENA-induced HCC rat model in
vivo, with a preferential superiority over conventional sorafenib.