Far-Red Light-Activatable Prodrug of Paclitaxel for the Combined Effects of Photodynamic Therapy and Site-Specific Paclitaxel Chemotherapy
Paclitaxel (PTX) is one of the most useful chemotherapeutic agents approved for several cancers, including ovarian, breast, pancreatic, and nonsmall cell lung cancer. However, it causes systemic side effects when administered parenterally. Photodynamic therapy (PDT) is a new strategy for treating lo...
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| Veröffentlicht in: | Journal of medicinal chemistry 2016-04, Vol.59 (7), p.3204-3214 |
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| container_issue | 7 |
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| container_title | Journal of medicinal chemistry |
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| creator | Thapa, Pritam Li, Mengjie Bio, Moses Rajaputra, Pallavi Nkepang, Gregory Sun, Yajing Woo, Sukyung You, Youngjae |
| description | Paclitaxel (PTX) is one of the most useful chemotherapeutic agents approved for several cancers, including ovarian, breast, pancreatic, and nonsmall cell lung cancer. However, it causes systemic side effects when administered parenterally. Photodynamic therapy (PDT) is a new strategy for treating local cancers using light and photosensitizer. Unfortunately, PDT is often followed by recurrence due to incomplete ablation of tumors. To overcome these problems, we prepared the far-red light-activatable prodrug of PTX by conjugating photosensitizer via singlet oxygen-cleavable aminoacrylate linker. Tubulin polymerization enhancement and cytotoxicity of prodrugs were dramatically reduced. However, once illuminated with far-red light, the prodrug effectively killed SKOV-3 ovarian cancer cells through the combined effects of PDT and locally released PTX. Ours is the first PTX prodrug that can be activated by singlet oxygen using tissue penetrable and clinically useful far-red light, which kills the cancer cells through the combined effects of PDT and site-specific PTX chemotherapy. |
| doi_str_mv | 10.1021/acs.jmedchem.5b01971 |
| format | Article |
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Med. Chem</addtitle><description>Paclitaxel (PTX) is one of the most useful chemotherapeutic agents approved for several cancers, including ovarian, breast, pancreatic, and nonsmall cell lung cancer. However, it causes systemic side effects when administered parenterally. Photodynamic therapy (PDT) is a new strategy for treating local cancers using light and photosensitizer. Unfortunately, PDT is often followed by recurrence due to incomplete ablation of tumors. To overcome these problems, we prepared the far-red light-activatable prodrug of PTX by conjugating photosensitizer via singlet oxygen-cleavable aminoacrylate linker. Tubulin polymerization enhancement and cytotoxicity of prodrugs were dramatically reduced. However, once illuminated with far-red light, the prodrug effectively killed SKOV-3 ovarian cancer cells through the combined effects of PDT and locally released PTX. 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| source | ACS Publications; MEDLINE |
| subjects | Antineoplastic Agents, Phytogenic - pharmacology Cell Line, Tumor Cell Proliferation - drug effects Female Humans Light Micelles Ovarian Neoplasms - drug therapy Ovarian Neoplasms - pathology Paclitaxel - pharmacology Photochemotherapy Photosensitizing Agents - pharmacology Prodrugs - pharmacology Tubulin - drug effects |
| title | Far-Red Light-Activatable Prodrug of Paclitaxel for the Combined Effects of Photodynamic Therapy and Site-Specific Paclitaxel Chemotherapy |
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