A highly effective self-supplying photosensitizer drug for deep-tissue metastatic tumours treatment

Due to the inherent defects of photodynamic therapy (PDT), its application in the treatment of deep-tissue metastatic tumours remains challenging. To extend the applicability of PDT, a novel chemiluminescent photosensitizer, Cy7-EOM, was developed by covalently coupling the photosensitizer Cy7 with a peroxycatechol derivative and encapsulating it within folate-modified and disulfide-containing nano-micelles. Upon targeted delivery and selective release, positive charged Cy7-EOM would target the mitochondria and efficiently generate singlet oxygen ( ¹ O ₂ ) via intramolecular chemiluminescence resonance energy transfer (CRET) by endogenous H ₂ O ₂ , directly inducing mitochondrial damage and cell apoptosis, realizing an efficient PDT for deep-tissue metastatic tumours. Remarkably, the covalent linkage between the donor and the acceptor greatly reduces the distance, significantly enhancing CRET efficiency. Moreover, the tumour-specific decomposition of the nano-micelles prevents aggregation-induced quenching and mitigates the diffusion barrier of ¹ O ₂ , while in normal tissues the integrality of nano-micelles shields the lethal effects of ¹ O ₂ . This method provides a new strategy for transforming adjuvant photosensitizers into direct therapeutic drugs, with significant potential for clinical application in the treatment of metastatic tumours.