Enhanced Therapeutic Efficacy of Folic Acid-Decorated Ti 3 C 2 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 nanocomposites, DOX/Ti 3 C 2 /PDA/PEG-FA, was developed for combined photothermal/chemotherapy (PTT/CHT) tumor treatment. The folic acid (FA)-modified nanomaterial facilitated specific targeting to folate receptor-overexpressing liver tumor cells, ensuring enhanced accumulation of the drug within the tumor site. Upon near-infrared (NIR) laser irradiation, the Ti 3 C 2 /PDA core exhibited efficient photothermal conversion, leading to rapid temperature elevation in the tumor region, while simultaneously triggering controlled DOX release due to photothermal and acidic stimulation, thereby promoting chemotherapy. In vitro results demonstrated that the DOX/Ti 3 C 2 /PDA/PEG-FA nanocomposites effectively inhibited the proliferation of HepG2 cells. Moreover, in vivo studies in the HepG2 xenograft mice model showed a significant reduction in 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 highlights the potential of DOX/Ti 3 C 2 /PDA/PEG-FA nanocomposites as a promising strategy for targeted cancer therapy, offering a synergistic approach to enhance liver cancer therapeutic outcomes while minimizing systemic toxicity.