title: In vitro photodynamic effects of scavenger receptor targeted-photoactivatable nanoagents on activated macrophages.
abstract: Scavenger receptors (SRs) expressed on the activated macrophages in inflammation sites have been considered as the most interesting and important target biomarker for targeted drug delivery, imaging and therapy. In the present study, we fabricated the scavenger receptor-A (SR-A) targeted-photoactivatable nanoagents (termed as Ce6/DS-DOCA) by entrapping chlorin e6 (Ce6) into the amphiphilic dextran sulfate-deoxycholic acid (DS-DOCA) conjugates via physically hydrophobic interactions. Insoluble Ce6 was easily encapsulated into DS-DOCA nanoparticles by a dialysis method and the loading efficiency was approximately 51.7%. The Ce6/DS-DOCA formed nano-sized self-assembled aggregates (28.8±5.6nm in diameter), confirmed by transmission electron microscope, UV/Vis and fluorescence spectrophotometer. The Ce6/DS-DOCA nanoagents could generate highly reactive singlet oxygen under laser irradiation. Also, in vitro studies showed that they were more specifically taken up by lipopolysaccharide (LPS)-induced activated macrophages (RAW 264.7) via a SR-A-mediated endocytosis, relative to by non-activated macrophages, and notably induced cell death of activated macrophages under laser irradiation. Therefore, SR-A targetable and photoactivatable Ce6/DS-DOCA nanoagents with more selective targeting to the activated macrophages will have great potential for treatment of inflammatory diseases.
authors.affiliation: Korea Basic Science Institute Chuncheon Center, Chuncheon, Gangwon 200-701, Republic of Korea; Interdisplinary Graduate Program for BIT Medical Convergence and Department of Biology, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon 200-701, Republic of Korea.
authors.forename: Bong Gu
authors.initials: BG
authors.lastname: Yi
authors.affiliation: Korea Basic Science Institute Chuncheon Center, Chuncheon, Gangwon 200-701, Republic of Korea.
authors.forename: Ok Kyu
authors.initials: OK
authors.lastname: Park
authors.affiliation: Korea Basic Science Institute Chuncheon Center, Chuncheon, Gangwon 200-701, Republic of Korea.
authors.forename: Myeong Seon
authors.initials: MS
authors.lastname: Jeong
authors.affiliation: Korea Basic Science Institute Chuncheon Center, Chuncheon, Gangwon 200-701, Republic of Korea.
authors.forename: Seung Hae
authors.initials: SH
authors.lastname: Kwon
authors.affiliation: Korea Basic Science Institute Chuncheon Center, Chuncheon, Gangwon 200-701, Republic of Korea.
authors.forename: Jae In
authors.initials: JI
authors.lastname: Jung
authors.affiliation: Korea Basic Science Institute Gwangju Center, Gwangju 500-757, Republic of Korea.
authors.forename: Seongsoo
authors.initials: S
authors.lastname: Lee
authors.affiliation: Interdisplinary Graduate Program for BIT Medical Convergence and Department of Biology, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon 200-701, Republic of Korea.
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Ryoo
authors.affiliation: Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Medical Center, Guro Hospital, #80, Guro-dong, Guro-gu, Seoul 152-703, Republic of Korea.
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Multimodal Imaging and Theranostic Laboratory, Cardiovascular Center, Korea University Guro Hospital, Seoul 152-703, Republic of Korea.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Korea Basic Science Institute Gwangju Center, Gwangju 500-757, Republic of Korea. Electronic address: wjmoon@kbsi.re.kr.
authors.forename: Won-Jin
authors.initials: WJ
authors.lastname: Moon
authors.affiliation: Korea Basic Science Institute Chuncheon Center, Chuncheon, Gangwon 200-701, Republic of Korea. Electronic address: kspark1223@kbsi.re.kr.
authors.forename: Kyeongsoon
authors.initials: K
authors.lastname: Park
mesh_terms: D000818:Animals; D001692:Biological Transport; D002735:Chlorophyllides; D003840:Deoxycholic Acid / Q000737:chemistry; D016264:Dextran Sulfate / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects* / Q000528:radiation effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects; D051379:Mice; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry*; D010778:Photochemotherapy; D011166:Porphyrins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism*; D012995:Solubility
chemical_list: D002735:Chlorophyllides; D004337:Drug Carriers; D008070:Lipopolysaccharides; D011166:Porphyrins; D012333:RNA, Messenger; D051117:Scavenger Receptors, Class A; D003840:Deoxycholic Acid; C062985:phytochlorin; D016264:Dextran Sulfate
keywords: Activated macrophages; Photoactivatable nanoagents; Scavenger receptor targeting