MXene-based CRISPR/Cas9 nanoplatform targeting FABP5 for ROS amplification and synergistic photothermal/photodynamic...

Area of Science:

• Biomedical Engineering
• Oncology
• Nanotechnology

Background:

• Cervical cancer poses a significant global health challenge, necessitating advanced therapeutic strategies.
• Photodynamic therapy (PDT) shows promise but is limited by cancer cells' antioxidant defenses.
• Fatty acid binding protein 5 (FABP5) is crucial for cervical cancer's oxidative stress tolerance.

Purpose of the Study:

• To develop a hybrid nanoplatform integrating gene editing and photothermal/photodynamic therapy for enhanced cervical cancer treatment.
• To investigate the synergistic effects of MXene-based photothermal/photodynamic therapy and CRISPR/Cas9-mediated FABP5 gene silencing.
• To evaluate the efficacy and biosafety of the developed nanoplatform in vitro and in vivo.

Main Methods:

• Fabrication of a MXene@PEI-FABP5 (MPF) nanoplatform for targeted delivery of CRISPR/Cas9.
• Utilizing MXene's photothermal and photodynamic properties under 808 nm laser irradiation.
• Silencing FABP5 expression in cervical cancer cells to disrupt antioxidant defenses.
• Assessing tumor inhibition rates and apoptosis induction in vitro and in vivo.

Main Results:

• The MPF nanoplatform effectively silenced FABP5 expression, reducing cellular antioxidant capacity.
• Combined photothermal/photodynamic therapy and gene editing resulted in significant oxidative stress amplification.
• An impressive tumor inhibition rate of approximately 96% was achieved with excellent biosafety.
• Cell death was predominantly induced through apoptosis in cancer cells.

Conclusions:

• The developed gene editing photonic nanoplatform offers a synergistic therapeutic approach for cervical cancer.
• This hybrid strategy overcomes limitations of conventional PDT by targeting cellular antioxidant mechanisms.
• The MPF nanoplatform presents a promising new paradigm for improving cervical cancer treatment outcomes.