期刊
CHEMMEDCHEM
卷 10, 期 2, 页码 304-311出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201402401
关键词
chemotherapy; conjugation; coumarin; photodynamic therapy; phthalocyanine
资金
- Technology Development Foundation of Fuzhou University [2011-XY-8, 2011-XY-6]
- Natural Science Foundation of Fujian Province [2012J05021]
- National Natural Science Foundation of China [21101028, 21201035]
- Major Project of the State Ministry of Science and Technology of China [2011ZX09101-001-04]
The combination of photodynamic therapy and chemotherapy is a promising strategy to overcome growing problems in contemporary medicine, such as low therapeutic efficacy and drug resistance. Four zinc(II) phthalocyanine-coumarin conjugates were synthesized and characterized. In these complexes, zinc(II) phthalocyanine was used as the photosensitizing unit, and a coumarin derivative was selected as the cytostatic moiety; the two components were linked via a tri(ethylene glycol) chain. These conjugates exhibit high photocytotoxicity against HepG2 human hepatocarcinoma cells, with low IC50 values in the range of 0.014-0.044 mu m. The high photodynamic activities of these conjugates are in accordance with their low aggregation tendency and high cellular uptake. One of these conjugates exhibits high photocytotoxicity and significantly higher chemocytotoxicity. The results clearly show that the two antitumor components in these conjugates work in a cooperative fashion. As shown by confocal microscopy, the conjugates can localize in the mitochondria and lysosomes, and one of the conjugates can also localize in the cell nuclei.
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