MXene-based CRISPR/Cas9 nanoplatform targeting FABP5 for ROS amplification and synergistic photothermal/photodynamic therapy of cervical cancer

Cervical cancer remains a leading cause of cancer-related mortality among women worldwide, underscoring the need for more effective therapeutic strategies. Photodynamic therapy (PDT) has gained attention in tumor treatment owing to its high selectivity and minimal invasiveness. However, PDT is often compromised by the intrinsic antioxidant defense systems of cervical cancer cells. Herein, we developed a gene editing photonic nanoplatform, MXene@PEI-FABP5 (MPF), which integrates the photothermal/photodynamic properties of MXene with CRISPR/Cas9-mediated FABP5 gene editing to achieve synergistically enhanced antitumor effects. Fatty acid binding protein 5 (FABP5), highly expressed in cervical cancer, plays a pivotal role in regulating lipid peroxidation and oxidative stress tolerance. By delivering the CRISPR/Cas9 system using MXene into tumor cells, FABP5 expression was effectively silenced, thereby disrupting cellular antioxidant defenses at the genetic level. Meanwhile, under 808 nm laser irradiation, MXene generated robust hyperthermia and reactive oxygen species (ROS), jointly amplifying oxidative stress and inducing cell death predominantly through apoptosis. Both in vitro and in vivo results demonstrated that MPF achieved an impressive tumor inhibition rate of ~96% while maintaining excellent biosafety. This work presents a "gene editing and photothermal/photodynamic" hybrid therapeutic paradigm, offering a promising avenue to overcome the limitations of conventional PDT and improve cervical cancer treatment outcomes.