ROS-Activatable siRNA-Engineered Polyplex for NIR-Triggered Synergistic Cancer Treatment

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapeutics

Background:

• Small interfering RNA (siRNA) and photodynamic therapy (PDT) show promise for cancer treatment but face challenges with effective delivery.
• Insufficient delivery of therapeutic agents to cancer cells limits the clinical application of siRNA and PDT.

Purpose of the Study:

• To engineer a novel reactive oxygen species (ROS)-activatable polyplex for combined siRNA-based gene silencing and PDT.
• To enhance the delivery and efficacy of siRNA and photosensitizer for hepatocellular carcinoma treatment.

Main Methods:

• Development of a PEGylated cationic polymer complex (PPTC/siRNA) containing a photosensitizer (Ce6) and RRM2-targeting siRNA.
• Utilizing near-infrared (NIR) light to trigger ROS generation, polyplex disassembly, and enhanced cellular uptake.
• Evaluating in vitro gene silencing and in vivo tumor inhibition in xenograft models.

Main Results:

• The polyplex efficiently delivered siRNA and photosensitizer, leading to effective gene silencing and photodynamic killing of cancer cells.
• PPTC/siRNA demonstrated synergistic inhibition of tumor growth in both cell line-derived and patient-derived xenograft models.
• The developed polyplex exhibited favorable safety profiles in cellular and animal studies.

Conclusions:

• The engineered ROS-activatable polyplex provides a novel strategy for combined RNA interference and PDT cancer therapy.
• NIR-triggered polyplex disassembly enhances therapeutic agent delivery and efficacy.
• This approach offers a promising platform for advanced cancer treatment with improved safety and effectiveness.