title: Biodistribution and in vivo toxicity of aptamer-loaded gold nanostars.
abstract: This paper reports an in vivo evaluation of toxicology and biodistribution of a highly anisotropic Au nanoconstruct composed of a gold nanostar (AuNS) core and a ligand shell of a G-quadruplex DNA aptamer AS1411 (Apt) supporting both targeting and therapy capabilities. We examined the toxicity of the nanoconstructs (Apt-AuNS) at four different injected concentrations. At the highest dose tested (48 mg/kg), maximal tolerated dose was not reached. Clinical pathology showed no apparent signs of acute toxicity. Interestingly, the nanoconstructs circulated longer in female rats compared to male rats. In two different tumor models, the biodistribution of Apt-AuNS, especially tumor accumulation, was different. Accumulation of Apt-AuNS was 5 times higher in invasive breast cancer tumors compared to fibrosarcoma tumors. These results provide insight on identifying a tumor model and nanoconstruct for in vivo studies, especially when an in vitro therapeutic response is observed in multiple cancer cell lines. From the clinical editor: This study investigated the toxicity and distribution of aptamer loaded gold nanostars in a rodent model of invasive breast cancer and fibrosarcoma. Acute toxicity was not identified even in the highest studied doses. Fivefold accumulation was demonstrated in the breast cancer model compared to the fibrosarcoma model. Studies like this are critically important in further clarifying the potential therapeutic use of these nanoconstructs, especially when ex vivo effects are clearly demonstrated.
authors.affiliation: Department of Chemistry, Northwestern University, Evanston, IL, USA.
authors.forename: Duncan Hieu M
authors.initials: DH
authors.lastname: Dam
authors.affiliation: Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA.
authors.forename: Kayla S B
authors.initials: KS
authors.lastname: Culver
authors.affiliation: Developmental Therapeutic Core, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA.
authors.forename: Irawati
authors.initials: I
authors.lastname: Kandela
authors.affiliation: Department of Chemistry, Northwestern University, Evanston, IL, USA.
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Lee
authors.affiliation: Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA.
authors.forename: Kavita
authors.initials: K
authors.lastname: Chandra
authors.affiliation: Department of Chemistry, Northwestern University, Evanston, IL, USA.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Developmental Therapeutic Core, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Mantis
authors.affiliation: Developmental Therapeutic Core, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA.
authors.forename: Andrey
authors.initials: A
authors.lastname: Ugolkov
authors.affiliation: Developmental Therapeutic Core, Chemistry of Life Processes Institute, Northwestern University, Evanston, IL, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Mazar
authors.affiliation: Department of Chemistry, Northwestern University, Evanston, IL, USA; Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA. Electronic address: todom@northwestern.edu.
authors.forename: Teri W
authors.initials: TW
authors.lastname: Odom
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006046:Gold / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D012727:Sex Characteristics
chemical_list: D052157:Aptamers, Nucleotide; D006046:Gold
keywords: Aptamer; Biodistribution; Gold nanoconstructs; Gold nanostars; Toxicity