A novel pheophorbide derivative, trimethyl-152-[L-aspartyl]pheophorbide a was synthesised and investigated for anti-tumor activity. The prepared photosensitizer had good absorption in the phototherapeutic window and high ROS yields. It exhibited excellent phototoxicity higher than reference compound m-THPC when irradiated by 650 nm light in vitro, and obvious photodynamic anti-tumor effect in vivo. It causes cellular apoptosis or necrosis under laser irradiation and localizes in mitochondria, lysosome, and endoplasmic reticulum. The observed high efficacy was rationalized by efficient introduction into the blood by facile transfer through membranes, which is supported by molecular dynamics simulation studies. This work provides a new candidate photosensitizer for anti-cancer treatment.

Department of Mathematics Informatics and Cybernetics University of Chemistry and Technology 16628 Prague Czech Republic

Department of Orthopedics Shanghai Bone Tumor Institution Shanghai General Hospital Shanghai Jiao Tong University School of Medicine 100 Haining Street Shanghai 200080 China

Department of Pharmaceutical Science and Technology Donghua University Shanghai 201620 China

Division of Organic Chemistry and Biochemistry Ruđer Bošković Institute Bijenička c 54 Zagreb 10000 Croatia

Present address Selvita d o o Prilaz baruna Filipovića 29 10000 Zagreb Croatia

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