title: Far-Red Light-Activatable Prodrug of Paclitaxel for the Combined Effects of Photodynamic Therapy and Site-Specific Paclitaxel Chemotherapy.
abstract: 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.
authors.affiliation: College of Pharmacy, University of Oklahoma Health Sciences Center , 1110 North Stonewall Avenue, Oklahoma City, Oklahoma 73117, United States.
authors.forename: Pritam
authors.initials: P
authors.lastname: Thapa
authors.affiliation: College of Pharmacy, University of Oklahoma Health Sciences Center , 1110 North Stonewall Avenue, Oklahoma City, Oklahoma 73117, United States.
authors.forename: Mengjie
authors.initials: M
authors.lastname: Li
authors.affiliation: College of Pharmacy, University of Oklahoma Health Sciences Center , 1110 North Stonewall Avenue, Oklahoma City, Oklahoma 73117, United States.
authors.forename: Moses
authors.initials: M
authors.lastname: Bio
authors.affiliation: College of Pharmacy, University of Oklahoma Health Sciences Center , 1110 North Stonewall Avenue, Oklahoma City, Oklahoma 73117, United States.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Rajaputra
authors.affiliation: College of Pharmacy, University of Oklahoma Health Sciences Center , 1110 North Stonewall Avenue, Oklahoma City, Oklahoma 73117, United States.
authors.forename: Gregory
authors.initials: G
authors.lastname: Nkepang
authors.affiliation: College of Pharmacy, University of Oklahoma Health Sciences Center , 1110 North Stonewall Avenue, Oklahoma City, Oklahoma 73117, United States.
authors.forename: Yajing
authors.initials: Y
authors.lastname: Sun
authors.affiliation: College of Pharmacy, University of Oklahoma Health Sciences Center , 1110 North Stonewall Avenue, Oklahoma City, Oklahoma 73117, United States.
authors.forename: Sukyung
authors.initials: S
authors.lastname: Woo
authors.affiliation: College of Pharmacy, University of Oklahoma Health Sciences Center , 1110 North Stonewall Avenue, Oklahoma City, Oklahoma 73117, United States.
authors.forename: Youngjae
authors.initials: Y
authors.lastname: You
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D008027:Light; D008823:Micelles; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology*; D014404:Tubulin / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D017319:Photosensitizing Agents; D011355:Prodrugs; D014404:Tubulin; D017239:Paclitaxel