Silicon Rhodamine-Catalyzed Near-Infrared Light-Induced Photodecaging of Ortho-Nitrobenzyl Groups In Vitro and In...

Area of Science:

• Photochemistry
• Chemical Biology
• Biomedical Engineering

Background:

• Ortho-nitrobenzyl (ONB) photocages offer spatiotemporal control but are limited by UV/blue light absorption, causing phototoxicity and poor tissue penetration.
• Existing photocaging strategies necessitate wavelengths that are detrimental to biological systems.

Purpose of the Study:

• To develop a near-infrared (NIR) light-triggered photodecaging method for ONB photocages.
• To overcome the limitations of UV/blue light activation for ONB photocages in biological applications.

Main Methods:

• Utilized silicon rhodamine (SiR) as a photoredox catalyst for NIR light-triggered ONB photodecaging.
• Investigated the reaction mechanism, revealing nitroreduction via single electron transfer and subsequent self-immolation.
• Applied the method to diverse substrates including amino acids, nucleotides, prodrugs, proteins, and fluorescent dyes.

Main Results:

• Achieved efficient uncaging of ONB substrates using 660 nm NIR light with high yields.
• Demonstrated successful application in mammalian cells and bacteria.
• Developed and validated a NIR-activated prodrug release system for antibody-drug conjugates (ADCs) in a tumor-bearing mouse model.

Conclusions:

• The novel SiR-catalyzed NIR photoredox system enables efficient and phototoxic-free uncaging of ONB photocages.
• This technology expands the utility of ONB photocages for advanced biological studies and therapeutic applications, including targeted cancer therapy.