Alkaline Phosphatase-Controllable and Red Light-Activated RNA Modification Approach for Precise Tumor Suppression

Area of Science:

• Biomedical Engineering
• Molecular Biology
• Cancer Research

Background:

• RNA interference (RNAi) shows therapeutic promise but faces challenges in delivery efficiency and stability.
• Developing advanced RNAi technologies is crucial for precise medicine and effective anti-tumor treatments.

Purpose of the Study:

• To develop a novel alkaline phosphatase (ALP)-controllable and red light-activated RNA modification (ALARM) approach for anti-tumor therapy.
• To design and synthesize an ALP-responsive probe (f-RCP) for targeted tumor detection and RNA modification.

Main Methods:

• Designed and synthesized f-RCP probe with tumor-targeting peptide, ALP-activated photosensitizer, and furan module.
• Investigated f-RCP's targeting to liver carcinoma HepG2 cells and ALP-triggered signal activation.
• Evaluated red light-induced singlet oxygen production and subsequent RNA modification leading to tumor cell apoptosis.

Main Results:

• f-RCP specifically targeted liver carcinoma cells and emitted signals upon ALP cleavage, enabling tumor detection.
• Red light activation of f-RCP generated singlet oxygen, inducing covalent RNA modification and mitochondrial damage.
• Significant tumor cell apoptosis and efficient tumor suppression were achieved through the ALARM strategy.

Conclusions:

• The ALARM approach offers a novel method for targeted cancer gene therapy by controllable RNA modification.
• This strategy demonstrates potential for sensitive tumor detection and effective anti-tumor treatment.
• Transcriptomic analysis provided initial insights into the therapeutic mechanism of the ALARM strategy.