title: Nanoparticle-protein complexes mimicking corona formation in ocular environment.
abstract: Nanoparticles adsorb biomolecules to form corona upon entering the biological environment. In this study, tissue-specific corona formation is provided as a way of controlling protein interaction with nanoparticles in vivo. In the vitreous, the composition of the corona was determined by the electrostatic and hydrophobic properties of the associated proteins, regardless of the material (gold and silica) or size (20- and 100-nm diameter) of the nanoparticles. To control protein adsorption, we pre-incubate 20-nm gold nanoparticles with 5 selectively enriched proteins from the corona, formed in the vitreous, to produce nanoparticle-protein complexes. Compared to bare nanoparticles, nanoparticle-protein complexes demonstrate improved binding to vascular endothelial growth factor (VEGF) in the vitreous. Furthermore, nanoparticle-protein complexes retain in vitro anti-angiogenic properties of bare nanoparticles. In particular, priming the nanoparticles (gold and silica) with tissue-specific corona proteins allows nanoparticle-protein complexes to exert better in vivo therapeutic effects by higher binding to VEGF than bare nanoparticles. These results suggest that controlled corona formation that mimics in vivo processes may be useful in the therapeutic use of nanomaterials in local environment.
authors.affiliation: Fight Against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Jo
authors.affiliation: Fight Against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, 03080, Republic of Korea.
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Center for Nano-Bio Measurement, Korea Research Institute of Standards and Science, Daejeon, 34113, Republic of Korea; Department of Chemistry and KI for the NanoCentury, KAIST, Daejeon, 34141, Republic of Korea.
authors.forename: Jin Gyeong
authors.initials: JG
authors.lastname: Son
authors.affiliation: Proteomics Core Facility, Clinical Research Institute, Seoul National University Hospital, Seoul, 03080, Republic of Korea.
authors.forename: Ki Soon
authors.initials: KS
authors.lastname: Dan
authors.affiliation: Department of Laboratory Medicine, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Song
authors.affiliation: Center for Nano-Bio Measurement, Korea Research Institute of Standards and Science, Daejeon, 34113, Republic of Korea. Electronic address: tglee@kriss.re.kr.
authors.forename: Tae Geol
authors.initials: TG
authors.lastname: Lee
authors.affiliation: Fight Against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, 03080, Republic of Korea; Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea; Department of Ophthalmology, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea. Electronic address: steph25@snu.ac.kr.
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000327:Adsorption; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000188:drug therapy / Q000473:pathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004285:Dogs; D006046:Gold / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011485:Protein Binding; D000066970:Protein Corona / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry; D013499:Surface Properties; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014822:Vitreous Body / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000066970:Protein Corona; D042461:Vascular Endothelial Growth Factor A; D006046:Gold; D012822:Silicon Dioxide
keywords: Corona; Nanomedicine; Nanoparticle; Nanoparticle-protein interaction