Light-triggered molecular mechanotherapy of tumor using membrane-mimicking conjugated oligoelectrolytes.

Sci Adv

Institute of Polymer Optoelectronic Materials and Devices, Guangdong Basic Research Center of Excellence for Energy & Information Polymer Materials, State Key Laboratory of Luminescent Materials and Devices, School of Materials Science and Engineering, South China University of Technology, Guangzhou

Published: August 2025


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Article Abstract

A class of light-mediated mechanotherapeutic agents was developed on the basis of conjugated oligoelectrolytes (COEs), which mimic the topology of lipid membranes and intrinsically exhibit excellent biocompatibility. Low-dose white light irradiation (20 milliwatts per square centimeter for 10 minutes) substantially decreased the half-maximal inhibitory concentration of the optimized COE against A549 cancer cells from more than 256 to 0.6 micromolar. Typical photodynamic and photothermal effects were not responsible for the potent anticancer efficacy. Biophysical and photophysical experiments using vesicle models revealed that COEs can induce mechanical force likely by molecular conformation change within lipid membranes under light exposure, supporting the mechanotherapeutic mechanism by which COEs after excitation can physically disrupt cell membrane. Investigation of two other COEs with similar spectral properties but different backbone architectures revealed that their mechanotherapeutic efficacy is dependent on molecular topology. These results highlight the potential to develop light-responsive mechanotherapeutic agents based on membrane-mimicking COE platform for cancer treatment.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12372874PMC
http://dx.doi.org/10.1126/sciadv.ady3349DOI Listing

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