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Twin-Tail Tadpole-Shaped Ce6-Peptide Conjugate for Enhanced Photodynamic Cancer Therapy

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Date 2025 Feb 5
PMID 39909401
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Abstract

Despite its therapeutic potential, photodynamic therapy faces several key limitations in clinical applications, including poor drug delivery and insufficient tumor selectivity. We engineered , a twin-tail peptide-photosensitizer conjugate that self-assembles into nanostructures for improved cancer treatment. By incorporating arginine-rich peptide sequences, this design not only enhances cellular internalization but also promotes peroxynitrite (ONOO) formation, amplifying the therapeutic effect. Our studies revealed that achieves 33-fold higher potency than unmodified Ce6, with an IC of 0.18 μM. The conjugate demonstrated selective accumulation in tumor tissue, robust ROS generation, and complete tumor regression in animal models while maintaining a favorable safety profile. These results establish as an innovative approach for advancing photodynamic therapy in cancer treatment.