title: Treatment of cancer micrometastasis using a multicomponent chain-like nanoparticle.
abstract: While potent cytotoxic agents are available to oncologists, the clinical utility of these agents is limited due to their non-specific distribution in the body and toxicity to normal tissues leading to use of suboptimal doses for eradication of metastatic disease. Furthermore, treatment of micrometastases is impeded by several biobarriers, including their small size and high dispersion to organs, making them nearly inaccessible to drugs. To circumvent these limitations in treating metastatic disease, we developed a multicomponent, flexible chain-like nanoparticle (termed nanochain) that possesses a unique ability to gain access to and be deposited at micrometastatic sites. Moreover, coupling nanochain particles to radiofrequency (RF)-triggered cargo delivery facilitated widespread delivery of drug into hard-to-reach cancer cells. Collectively, these features synergistically facilitate effective treatment and ultimately eradication of micrometastatic disease using a low dose of a cytotoxic drug.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Radiology, Case Western Reserve University, Cleveland, OH 44106, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Pubudu M
authors.initials: PM
authors.lastname: Peiris
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Randall
authors.initials: R
authors.lastname: Toy
authors.affiliation: Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Abramowski
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Pete
authors.initials: P
authors.lastname: Vicente
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Tucci
authors.affiliation: Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Physics, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bauer
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Mayer
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Morgan
authors.initials: M
authors.lastname: Tam
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Doolittle
authors.affiliation: Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Pansky
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Tran
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Dishen
authors.initials: D
authors.lastname: Lin
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: William P
authors.initials: WP
authors.lastname: Schiemann
authors.affiliation: Edward B. Singleton Department of Pediatric Radiology, Texas Children's Hospital, Houston, TX 77030, USA; Department of Radiology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Ketan B
authors.initials: KB
authors.lastname: Ghaghada
authors.affiliation: Department of Radiology, Case Western Reserve University, Cleveland, OH 44106, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Griswold
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Radiology, Case Western Reserve University, Cleveland, OH 44106, USA; Case Center for Imaging Research, Case Western Reserve University, Cleveland, OH 44106, USA; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: stathis@case.edu.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Karathanasis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001940:Breast / Q000187:drug effects / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D061206:Neoplasm Micrometastasis / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer metastasis; Chain-like nanoparticle; Nanochains; Radiofrequency-triggered drug release; Targeting