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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. 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