Multifunctional sorafenib-loaded MXene for enhanced cancer therapy: In vitro and in vivo study based on chemotherapy/photothermal therapy approach

Abstract

Cancer, characterized by uncontrolled cell proliferation, remains one of the deadliest diseases. Multifunctional hybrid nanosystems that combine drugs with photothermal therapy (PTT) offer enhanced tumor treatment options through localized thermal increase and smart drug delivery (SDD). MXene, a 2D inorganic nanomaterial consisting of titanium carbide (Ti₃C₂), has garnered significant interest for cancer applications. MXene was combined with the metal–organic framework MOF-UiO-67 to create MX-Uio-67. The anticancer drug sorafenib (SN) was then load onto MX-UiO-67 and coated with chitosan (CS) to form SN-MX-UiO-67@CS aiming to improve chemo-PTT mediated by near-infrared (NIR) laser irradiation. The release of SN from SN-MX-UiO-67@CS was studied at pH 4.6 and pH 7.4 conditions, both with and without NIR, over a period of 96 h. The cumulative release of SN from MX-UiO-67@CS reached 80.16 % at pH 7.4 and 93.77 % at pH 4.6 under NIR irradiation. MTT assay results demonstrated significant cytotoxicity against HepG2 cells, with SN-MX-UiO-67@CS (chemo-PTT) displaying an IC₅₀ value of 22.4 µg/mL and achieving a necrosis was 36.1 % and apoptosis rate of 50.94 %, highlighting its potential as an effective anticancer agent. Furthermore, in vivo PTT via xenograft model and biodistribution studies were performed in healthy BALB/c mice under NIR. A bio-analytical technique was established utilizing HepG2 cells for the quantitative examination of SN in mice plasma, spleen, liver, heart, kidneys, tumor and lungs. A highly significant difference was observed in the plasma concentration–time curves and pharmacokinetic parameters of SN, SN-MX, and SN-MX-UiO-67following the intravenous administration of SN-MX-UiO-67@CS. Notably, the formulation exhibited higher key pharmacokinetic parameters, involving C_max and AUC_(0-72).