Pheophorbide-a conjugates with cancer-targeting moieties for targeted photodynamic cancer therapy

作者：You Hyun; Yoon Hyo Eun; Jeong Pyeong Hwa; Ko Hyojin^*; Yoon Jung Hoon; Kim Yong Chul

来源：Bioorganic & Medicinal Chemistry, 2015, 23(7): 1453-1462.

DOI：10.1016/j.bmc.2015.02.014

• Pheophorbide-a
• Conjugate
• Fluorescence
• Apoptosis
• PDT

Pheophorbide-a, a non-selective photosensitizer, was conjugated with cancer-targeting moieties, such as folic acid, the CRGDLASLC peptide, the cRGDfK peptide and leuprorelin, for the purpose of targeted photodynamic cancer therapy. The cellular uptake of pheophorbide-a conjugates in cancer cells overexpressing the corresponding receptors of the targeting moieties was largely enhanced compared with that in the receptor-negative cells. In the study of in vitro photodynamic activity and selectivity of pheophorbide-a conjugates in the receptor-positive and receptor-negative cells, a pheophorbide-a conjugate, (14) with an alpha(v)beta(6) ligand (CRGDLASLC) exhibited the highest selectivity in the positive FaDu cells. Targeted PDT with 14 induced cell death through apoptosis and morphological apoptosis-like characteristics. These results suggest that pheophorbide-a conjugate 14 could be utilized in selective photodynamic therapy for oral cancers primarily expressing the alpha(v)beta(6) receptor.

• 出版日期2015-4-1