title: Tumor Presence Induces Global Immune Changes and Enhances Nanoparticle Clearance.
abstract: Long-circulating nanoparticles are essential for increasing tumor accumulation to provide therapeutic efficacy. While it is known that tumor presence can alter the immune system, very few studies have explored this impact on nanoparticle circulation. In this report, we demonstrate how the presence of a tumor can change the local and global immune system, which dramatically increases particle clearance. We found that tumor presence significantly increased clearance of PRINT hydrogel nanoparticles from the circulation, resulting in increased accumulation in the liver and spleen, due to an increase in M2-like macrophages. Our findings highlight the need to better understand interactions between immune status and nanoparticle clearance, and suggest that further consideration of immune function is required for success in preclinical and clinical nanoparticle studies.
authors.affiliation: Department of Chemical and Biomolecular Engineering, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Kai
authors.forename: Hailey E
authors.initials: HE
authors.lastname: Brighton
authors.affiliation: Department of Chemical and Biomolecular Engineering, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Fromen
authors.forename: Tammy W
authors.initials: TW
authors.lastname: Shen
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Luft
authors.forename: Yancey E
authors.initials: YE
authors.lastname: Luft
authors.forename: Amanda W
authors.initials: AW
authors.lastname: Keeler
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Robbins
authors.forename: Jenny P Y
authors.initials: JP
authors.lastname: Ting
authors.forename: William C
authors.initials: WC
authors.lastname: Zamboni
authors.forename: James E
authors.initials: JE
authors.lastname: Bear
authors.affiliation: Department of Chemical and Biomolecular Engineering, North Carolina State University , Raleigh, North Carolina 27695, United States.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: DeSimone
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D002945:Cisplatin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D004339:Drug Compounding; D004423:Ear / Q000033:anatomy & histology / Q000098:blood supply; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D007113:Immunity, Innate; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D009368:Neoplasm Transplantation; D061251:Primary Cell Culture; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D059008:Time-Lapse Imaging
chemical_list: D000970:Antineoplastic Agents; D020100:Hydrogels; D002945:Cisplatin
keywords: immunology; intravital; nanoparticle; orthotopic; pharmacokinetic