RBC membrane-coated sorafenib-MXene-Au nanocomposites for synergistic chemo-photothermal therapy of liver cancer

Red blood cell (RBC) membrane has emerged as innovative biological nanocarriers. In this study, RBCs membrane-coated sorafenib (SF)-MXene-Au nanocomposite (SF-MX-Au@RBCs), was developed as a smart drug delivery (SDD) system, offering enhanced photothermal therapy (PTT) under near-infrared (NIR) irradiation. The synthesized SF-MX-Au@RBCs exhibited an average size of approximately 65 nm and a zeta potential of −22.11 mV. The cumulative SF release from SF-MX-Au@RBCs reached 61.4 % under NIR irradiation at pH 7.4 over 96 h. Furthermore, the treatment effectiveness of SF-MX-Au@RBCs as a chemo-PTT treatment was evaluated against HepG2 liver cancer cells. In vitro assay demonstrated significant cytotoxicity, with chemo-PTT achieving an IC₅₀ value of 7.3 μg/mL and leading to necrosis rates of 31.9 % while the total apoptosis rates was 56.3 % (29.5 % late and 26.8 % early apoptosis) in treated cells. Western blot analysis indicated significant suppression of phosphorylated ERK (p-ERK) and MEK (p-MEK) in the MEK/ERK signaling pathway, with greater inhibition observed in the SF-MX-Au@RBCs group compared to SF alone. Additionally, key angiogenesis-related proteins, involving VEGFR2, VEGFR3, and PDGFR, were downregulated, highlighting the superior antiangiogenic effects of the nanocomposite. In vivo studies utilizing a xenograft model in BALB/c mice under NIR revealed that the chemo-PTT treatment indicated the smallest tumor volume (140 mm³) and tumor weight (0.16 g) compared to the other treatment groups. The chemo-PTT approach significantly enhanced antitumor efficacy, highlighting the potential for further optimization and improved treatment outcomes through targeted drug delivery systems (DDS). In addition, a comprehensive molecular docking analysis was conducted to examine the binding interactions of SF and MXene with three crucial proteins, namely: RAF proto-oncogene serine/threonine-protein kinase, FGR tyrosine-protein kinase, and mitogen-activated protein kinase (MAPK). MXene demonstrated superior binding affinities across the investigated target proteins, with ΔG values ranging from −11.94 to −12.56 kcal/mol.