title: Imaging the delivery of drug-loaded, iron-stabilized micelles.
abstract: Nanoparticle drug carriers hold potential to improve current cancer therapy by delivering payload to the tumor environment and decreasing toxic side effects. Challenges in nanotechnology drug delivery include plasma instability, site-specific delivery, and relevant biomarkers. We have developed a triblock polymer comprising a hydroxamic acid functionalized center block that chelates iron to form a stabilized micelle that physically entraps chemotherapeutic drugs in the hydrophobic core. The iron-imparted stability significantly improves the integrity of the micelle and extends circulation pharmacokinetics in plasma over that of free drug. Furthermore, the paramagnetic properties of the iron-crosslinking exhibits contrast in the tumors for imaging by magnetic resonance. Three separate nanoparticle formulations demonstrate improved anti-tumor efficacy in xenograft models and decreased toxicity. We report a stabilized polymer micelle that improves the tolerability and efficacy of chemotherapeutic drugs, and holds potential for non-invasive MRI to image drug delivery and deposition in the tumor.
authors.affiliation: Intezyne Technologies, Tampa, FL, USA. Electronic address: suzanne.bakewell@intezyne.com.
authors.forename: Suzanne J
authors.initials: SJ
authors.lastname: Bakewell
authors.affiliation: Intezyne Technologies, Tampa, FL, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Carie
authors.affiliation: Intezyne Technologies, Tampa, FL, USA.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Costich
authors.affiliation: Intezyne Technologies, Tampa, FL, USA.
authors.forename: Jyothi
authors.initials: J
authors.lastname: Sethuraman
authors.affiliation: Intezyne Technologies, Tampa, FL, USA.
authors.forename: J Edward
authors.initials: JE
authors.lastname: Semple
authors.affiliation: Intezyne Technologies, Tampa, FL, USA.
authors.forename: Bradford
authors.initials: B
authors.lastname: Sullivan
authors.affiliation: Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
authors.forename: Gary V
authors.initials: GV
authors.lastname: Martinez
authors.affiliation: Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
authors.forename: William
authors.initials: W
authors.lastname: Dominguez-Viqueira
authors.affiliation: Intezyne Technologies, Tampa, FL, USA.
authors.forename: Kevin N
authors.initials: KN
authors.lastname: Sill
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007501:Iron / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D008819:Mice, Nude; D008823:Micelles; D011108:Polymers / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D007501:Iron
keywords: Chemotherapeutics; Iron-stabilization; MRI agent; Polymer micelle; Targeted delivery