title: Antioxidant-photosensitizer dual-loaded polymeric micelles with controllable production of reactive oxygen species.
abstract: Poly(ethylene glycol)-b-poly(caprolactone) (PEG-b-PCL) micelles dually loaded with both pheophorbide a (PhA) as a photosensitizer and β-carotene (CAR) as a singlet oxygen ((1)O2) scavenger were designed to control photodynamic therapy (PDT) activity in cancer treatment. The CAR in the PhA/CAR micelles significantly diminished PhA-generated (1)O2 through direct (1)O2 scavenging, whereas the CAR molecules lost their (1)O2 scavenging activity when the PhA and CAR were spatially isolated by the disintegration of the PEG-b-PCL micelles. In cell-culture systems, light irradiation at a post-treatment time that corresponded to the presence of the micelles in the blood environment induced negligible phototoxicity, whereas light irradiation at a post-treatment time that corresponded to the presence of the micelles in the intracellular environment induced remarkable phototoxicity. In addition, a longer post-treatment time induced greater internalization of PhA/CAR micelles, which resulted in higher phototoxicity, suggesting an increase in photo killing activity against the tumor cells of interest. Thus, the co-loading of a (1)O2 generator and a (1)O2 scavenger into a single micelle is a potential strategy that may be useful in facilitating more accurate and reliable PDT with site-specific controllable production of singlet oxygen species for cancer treatment.
authors.affiliation: Department of Polymer Science and Engineering, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764, Republic of Korea.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Polymer Science and Engineering, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764, Republic of Korea.
authors.forename: Kwon Hyeok
authors.initials: KH
authors.lastname: Yoon
authors.affiliation: Department of Pharmacy and Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea. Electronic address: hckang@catholic.ac.kr.
authors.forename: Han Chang
authors.initials: HC
authors.lastname: Kang
authors.affiliation: Department of Polymer Science and Engineering, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 305-764, Republic of Korea. Electronic address: khuh@cnu.ac.kr.
authors.forename: Kang Moo
authors.initials: KM
authors.lastname: Huh
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002734:Chlorophyll / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D004338:Drug Combinations; D004339:Drug Compounding; D005026:Ethylene Glycols / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D011091:Polyesters / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013499:Surface Properties; D019207:beta Carotene / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004338:Drug Combinations; D005026:Ethylene Glycols; D016166:Free Radical Scavengers; D017319:Photosensitizing Agents; D011091:Polyesters; D017382:Reactive Oxygen Species; C476300:poly(epsilon-caprolactone)-b-poly(ethylene glycol); D019207:beta Carotene; D002734:Chlorophyll; C032623:pheophorbide a
keywords: Antioxidant; Photodynamic therapy; Polymeric micelles; Scavenging; Singlet oxygen