title: Folic Acid-Conjugated Pyropheophorbide a as the Photosensitizer Tested for In Vivo Targeted Photodynamic Therapy.
abstract: Photodynamic therapy (PDT) is a highly localized and minimally invasive cancer treatment modality with many important advantages, but the lack of ideal photosensitizers (PSs) greatly restricts its clinical utility. To develop new PSs with highly efficient singlet oxygen production and high tumor-localizing ability to reduce damage to healthy adjacent tissues, we conjugated folic acid (FA) with pyropheophorbide a (Pyro), a potent PS with a very high singlet oxygen quantum yield and a high extinction coefficient. In the present work, we describe the synthesis and PDT evaluation of this FA-Pyro conjugate both in vitro and in vivo. This conjugation increased the accumulation of Pyro inside the tumors and improved the efficiency of PDT, resulting in eradication of subcutaneous xenograft KB (human mouth epidermal carcinoma) tumors after only 1 or 2 applications of external near infrared light irradiation. This outstanding PDT outcome in a tumor-bearing mouse model and the simple synthesis of the conjugate should have very good practical potential for clinical application.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, People's Republic of China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Kanghong Yaoyuan Biotech Co., Ltd, Tianjin, People's Republic of China. Electronic address: hwq0324@hotmail.com.
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, People's Republic of China. Electronic address: hongzy@nankai.edu.cn.
authors.forename: Zhangyong
authors.initials: Z
authors.lastname: Hong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005492:Folic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008807:Mice, Inbred BALB C; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D017319:Photosensitizing Agents; D002734:Chlorophyll; C040298:pyropheophorbide a; D005492:Folic Acid
keywords: folate receptor; photodynamic therapy; pyropheophorbide a