A dual activatable photosensitizer toward targeted photodynamic therapy.

Abstract

An unsymmetrical bisferrocenyl silicon(IV) phthalocyanine has been prepared in which the disulfide and hydrazone linkers can be cleaved by dithiothreitol and acid, respectively. The separation of the ferrocenyl quenchers and the phthalocyanine core greatly enhances the fluorescence emission, singlet oxygen production, intracellular fluorescence intensity, and in vitro photocytotoxicity. The results have been compared with those for the two symmetrical analogues which contain either the disulfide or hydrazone linker and therefore can only be activated by one of these stimuli. For the dual activatable agent, the greatest enhancement can be attained under a slightly acidic environment (pH = 4.5-6.8) and in the presence of dithiothreitol (in millimolar range), which can roughly mimic the acidic and reducing environment of tumor tissues. This compound can also be activated in tumor-bearing nude mice. It exhibits an increase in fluorescence intensity in the tumor over the first 10 h after intratumoral injection and can effectively inhibit the growth of tumor upon illumination.

• Authors: Janet T F Lau, Pui-Chi Lo, Xiong-Jie Jiang, Qiong Wang, Dennis K P Ng
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 57 Issue 10 Pg. 4088-97 (May 22 2014) ISSN: 1520-4804 [Electronic] United States
• PMID: 24793456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Photosensitizing Agents
• Dithiothreitol

Topics

• Animals
• Cell Line, Tumor
• Dithiothreitol (pharmacology)
• Female
• HT29 Cells
• Humans
• Hydrogen-Ion Concentration
• Mice
• Mice, Inbred BALB C
• Neoplasms, Experimental (drug therapy)
• Photochemotherapy
• Photosensitizing Agents (chemical synthesis, chemistry, pharmacology)