title: Physiological function and inflamed-brain migration of mouse monocyte-derived macrophages following cellular uptake of superparamagnetic iron oxide nanoparticles-Implication of macrophage-based drug delivery into the central nervous system.
abstract: This study was designed to use superparamagnetic iron oxide nanoparticles (SPIONs) as evaluating tools to study monocyte-derived macrophages (MDM)-mediated delivery of small molecular agents into the diseased brains. MDM were tested with different-configured SPIONs at selected concentrations for their impacts on carrier cells' physiological and migratory properties, which were found to depend largely on particle size, coating, and treatment concentrations. SHP30, a SPION of 30-nm core size with oleic acids plus amphiphilic polymer coating, was identified to have high cellular uptake efficiency and cause little cytotoxic effects on MDM. At lower incubation dose (25μg/mL), few alteration was observed in carrier cells' physiological and in vivo migratory functions, as tested in a lipopolysaccharide-induced acute neuroinflammation mouse model. Nevertheless, significant increase in monocyte-to-macrophage differentiation, and decrease in in vivo carrier MDM inflamed-brain homing ability were found in groups treated with a higher dose of SHP30at 100μg/mL. Overall, our results have identified MDM treatment at 25μg/mL SHP30 resulted in little functional changes, provided valuable parameters for using SPIONs as evaluating tools to study MDM-mediated therapeutics carriage and delivery, and supported the concepts of using monocytes-macrophages as cellular vehicles to transport small molecular agents to the brain.
authors.affiliation: Office of Public Health Studies, University of Hawaii at Manoa, Honolulu, HI 96822, USA; Department of Microbiology, University of Hawaii at Manoa, Honolulu, HI 96822, USA. Electronic address: hsini@hawaii.edu.
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Tong
authors.affiliation: Office of Public Health Studies, University of Hawaii at Manoa, Honolulu, HI 96822, USA. Electronic address: kangwenkevin@gmail.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Kang
authors.affiliation: Office of Public Health Studies, University of Hawaii at Manoa, Honolulu, HI 96822, USA. Electronic address: angelsighyl@gmail.com.
authors.forename: Yingli
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Office of Public Health Studies, University of Hawaii at Manoa, Honolulu, HI 96822, USA. Electronic address: gzzhou@163.com.
authors.forename: Guangzhou
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Office of Public Health Studies, University of Hawaii at Manoa, Honolulu, HI 96822, USA. Electronic address: yuanan@hawaii.edu.
authors.forename: Yuanan
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005290:Ferric Compounds / Q000737:chemistry*; D007249:Inflammation / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000378:metabolism; D058185:Magnetite Nanoparticles; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology; D009829:Oleic Acids / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D005290:Ferric Compounds; D008070:Lipopolysaccharides; D058185:Magnetite Nanoparticles; D009829:Oleic Acids; D011108:Polymers; C000499:ferric oxide
keywords: Monocyte-macrophage brain migration; Monocyte-macrophage drug delivery; Nanoparticle size; Nanoparticle surface coating; Neuroinflammation; SPIONs