title: Selective photosensitizer delivery into plasma membrane for effective photodynamic therapy.
abstract: Subcellular localization of photosensitizers (PSs) determines the therapeutic efficacy in the photodynamic therapy. However, among the subcellular compartments, there has been little effort to deliver the PSs selectively into the plasma membrane and examine the phototherapeutic efficacy of membrane-localized PSs. Here, we developed a liposomal delivery system to localize the hydrophobic PSs selectively into the plasma membrane. The membrane fusogenic liposomes (MFLs), the membrane of which is engineered to fuse with the plasma membrane, was prepared for the membrane localization of PSs. The phototherapeutic efficacy of cells treated with ZnPc-loaded MFLs was superior over that of cells treated with ZnPc-loaded non-fusogenic liposomes, which is the conventional liposomal formulation that delivers the PSs into the intracellular compartments via endocytosis. The membrane localization of ZnPc molecules led to rapid membrane disruption upon irradiation and subsequent necrosis-like cell death. The membrane-localized generation of reactive oxygen species in the cells treated with ZnPc-loaded MFLs was likely to account for the effective disruption of plasma membrane. Thus, this work provides a novel delivery method to localize the PSs selectively into the plasma membrane with the enhanced phototherapeutic efficacy.
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea; KAIST Institute for Optical Science and Technology, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea; KAIST Institute for Optical Science and Technology, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea.
authors.forename: Olavo Amorim
authors.initials: OA
authors.lastname: Santos
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea; KAIST Institute for Optical Science and Technology, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea; KAIST Institute for the NanoCentury, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea. Electronic address: jihopark@kaist.ac.kr.
authors.forename: Ji-Ho
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D054833:Isoindoles; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D008561:Membrane Fusion; D051379:Mice; D009336:Necrosis; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods; D017967:Zinc Compounds
chemical_list: D007211:Indoles; D054833:Isoindoles; D008055:Lipids; D008081:Liposomes; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D017967:Zinc Compounds; C052159:Zn(II)-phthalocyanine
keywords: Cancer; Drug delivery; Membrane fusogenic liposome; Photodynamic therapy; Photosensitizer