Enhanced therapeutic efficacy of folic acid-decorated Ti3C2 MXenes in targeted combination therapy for liver cancer

Abstract

The limited efficacy and potential off-target toxicity of nanotherapeutic drugs remain significant challenges in liver cancer treatment. To address these issues, a novel targeted therapy approach utilizing a multifunctional nanocomposite, DOX/Ti₃C₂/PDA/PEG–FA, was developed for combined photothermal/chemotherapy (PTT/CHT) tumor treatment. The folic acid (FA)-modified nanomaterial facilitated specific targeting of folate receptor-overexpressing liver tumor cells, ensuring enhanced accumulation of the drug within the tumor site. Upon near-infrared (NIR) laser irradiation, the Ti₃C₂/PDA core exhibited efficient photothermal conversion, leading to a rapid temperature elevation in the tumor region while simultaneously triggering controlled DOX release due to the photothermal and acidic stimulation, thereby promoting chemotherapy. In vitro results demonstrated that the DOX/Ti₃C₂/PDA/PEG–FA nanocomposites effectively inhibited the proliferation of HepG2 cells. Moreover, in vivo studies in the HepG2 xenograft mouse model showed a significant reduction in the tumor volume and complete tumor ablation with minimal side effects, indicating the high efficiency and low toxicity of the targeted PTT/CHT combination therapy. This study introduces a novel DOX/Ti₃C₂/PDA/PEG–FA nanoplatform, which paves the way for targeted cancer therapy through a synergistic mechanism, significantly improving therapeutic efficacy against liver cancer while concurrently reducing systemic adverse effects.