Endogenous and exogeneous stimuli-triggered reactive oxygen species evoke long-lived carbon monoxide to fight against...

Area of Science:

• Nanotechnology
• Biomedical Engineering
• Cancer Therapy

Background:

• Reactive oxygen species (ROS)-based cancer therapies face challenges with insufficient ROS levels and short ROS half-lives.
• Existing approaches have not simultaneously addressed both limitations for enhanced efficacy.

Purpose of the Study:

• To develop a nanotherapeutic platform that synchronously elevates ROS levels and generates carbon monoxide (CO) to overcome limitations in ROS-associated cancer treatment.
• To investigate the efficacy of this platform in suppressing lung cancer progression, recurrence, and metastasis.

Main Methods:

• Construction of a nanotherapeutic platform using hollow manganese dioxide (H-MnO2) carriers loaded with chlorin e6 (Ce6) and a CO donor (Mn2(CO)10).
• Utilizing intratumoral H2O2 and ultrasound to trigger H-MnO2 and Ce6 for ROS production (•OH and 1O2).
• Employing cascade catalysis for ROS to CO conversion, enhancing therapeutic effects and investigating molecular mechanisms via proteomic and genomic analyses.

Main Results:

• The nanotherapeutic platform effectively elevated ROS levels and produced long-lived CO, converting short-lived ROS.
• Demonstrated significant suppression of lung cancer progression, recurrence, and metastasis, leading to a prolonged survival rate.
• Uncovered CO-induced activation of AKT signaling, NRF-2 phosphorylation, and HMOX-1 overexpression, contributing to mitochondrial dysfunction and enhanced anti-tumor effects.

Conclusions:

• The developed cascade catalysis strategy offers a novel approach to enrich ROS and trigger CO release for treating refractory cancers.
• This multichannel nanotherapeutic platform shows promise for overcoming limitations in current ROS-associated anticancer strategies.
• The findings highlight the potential of synergistic ROS and CO generation for robust anti-cancer outcomes.