MXene-encapsulated ZIF-8@Liposomes for NIR-enhanced photothermal therapy in hepatocellular carcinoma treatment: In vitro, in vivo, and in silico study

Photothermal therapy (PTT) utilizes near-infrared (NIR) light to enhance localized, non-invasive cancer treatments and drug delivery systems (DDS). Combination chemotherapy with PTT (chemo-PTT) offers multiple therapeutic advantages, involving synergistic effects, reduced side effects, and decreased drug toxicity. In this study, 2D titanium carbide (Ti₃C₂T_x) MXene nanosheets were encapsulated in a zeolitic imidazolate framework-8 (ZIF-8) to form (MX-ZIF-8) nanoparticles (NPs) for PTT applications. Sorafenib (SB), an anticancer drug was loaded onto MX-ZIF-8 and further modified with a liposomes (LPs) lipid bilayer to create (SB-MX-ZIF-8@LPs) nanocomposites. TEM imaging revealed that SB-MX-ZIF-8@LPs had a lamellar structure and spherical shape, with an average diameter of 75.2 nm and a zeta potential (ZP) of −8.4 ± 4.5 mV. Additionally, the PT stability, drug encapsulation, and in-vitro release kinetics of SB-MX-ZIF-8@LPs were assessed. These nanocomposites exhibited an impressive PT conversion efficiency of 55 % at 50 μg/mL under NIR irradiation. The cumulative release of SB from SB-MX-ZIF-8@LPs reached 86.15 % at pH 7.4 and 89.3 % at pH 4.8 under NIR over a period of 72 h, with an encapsulation efficiency of 87.34 %. MTT assays revealed strong cytotoxicity against HepG2 cells, with SB-MX-ZIF-8@LPs showing an IC₅₀ value of 2.7 μg/mL and inducing approximately 96 % total apoptosis. The SB-MX-ZIF-8@lip nanocomposite demonstrated excellent biological stability in a serum environment, retaining over 98 % of sorafenib and maintaining consistent particle size (∼347 nm) over 30 days. An in vivo xenograft study in BALB/c mice further demonstrated the efficacy of SB-MX-ZIF-8@LPs, with this treatment group showing the smallest tumor volume compared to other groups and a significantly higher tumor volume reduction than SB alone. Molecular docking studies indicated that SB exhibited strong binding affinities particularly with ABL1 (−8.7 kcal/mol) and EGFR (−9.3 kcal/mol). Docking interactions between MXene and SB, conducted using the Hdock Server, resulted in a docking score of −10.53, with one bond forming at a distance of 4 Å. These findings were consistent with experimental results, highlighting the favorable interaction between MXene and SB. ADMET analysis confirmed that MX-ZIF-8@LPs possessed favorable drug carrier properties, including high intestinal absorption (96.6 %), and low toxicity supporting its potential as an effective DDS for cancer therapy.