NIR Light-Mediated Mitochondrial RNA Modification for Cancer RNA Interference Therapeutics

Area of Science:

• Biomedical Engineering
• Molecular Biology
• Cancer Research

Background:

• Mitochondrial RNA (mtRNA) is crucial for mitochondrial protein synthesis.
• Interfering with mtRNA can effectively induce cancer cell apoptosis.
• Targeting mtRNA presents a potential therapeutic strategy for cancer treatment.

Purpose of the Study:

• To develop a near-infrared (NIR) light-mediated approach for mitochondrial RNA modification.
• To create a tumor-targetable probe for long-term imaging and effective tumor suppression.
• To investigate the potential of mtRNA modification as a cancer RNA interference therapeutic.

Main Methods:

• Designed and synthesized a NIR fluorescent probe (f-CRI) incorporating a cyclic RGD peptide, IR780 fluorophore, and a singlet oxygen-labile furan group.
• Demonstrated probe accumulation in cellular mitochondria.
• Utilized 808 nm irradiation to covalently conjugate the probe onto mtRNA, enabling long-term retention in tumors.

Main Results:

• The f-CRI probe predominantly localized to mitochondria.
• NIR irradiation induced covalent conjugation of f-CRI to mtRNA, leading to prolonged tumor retention.
• Covalent modification of mtRNA perturbed mitochondrial function, resulting in significant tumor suppression.

Conclusions:

• NIR light-mediated mtRNA modification using the f-CRI probe is effective for tumor imaging and suppression.
• This approach offers a promising strategy for developing cancer RNA interference therapeutics.
• The study highlights the potential of targeting mtRNA for long-term cancer treatment.