title: Vascular Targeting of a Gold Nanoparticle to Breast Cancer Metastasis.
abstract: The vast majority of breast cancer deaths are due to metastatic disease. Although deep tissue targeting of nanoparticles is suitable for some primary tumors, vascular targeting may be a more attractive strategy for micrometastasis. This study combined a vascular targeting strategy with the enhanced targeting capabilities of a nanoparticle to evaluate the ability of a gold nanoparticle (AuNP) to specifically target the early spread of metastatic disease. As a ligand for the vascular targeting strategy, we utilized a peptide targeting alpha(v) beta(3) integrin, which is functionally linked to the development of micrometastases at a distal site. By employing a straightforward radiolabeling method to incorporate Technetium-99m into the AuNPs, we used the high sensitivity of radionuclide imaging to monitor the longitudinal accumulation of the nanoparticles in metastatic sites. Animal and histological studies showed that vascular targeting of the nanoparticle facilitated highly accurate targeting of micrometastasis in the 4T1 mouse model of breast cancer metastasis using radionuclide imaging and a low dose of the nanoparticle. Because of the efficient targeting scheme, 14% of the injected AuNP deposited at metastatic sites in the lungs within 60 min after injection, indicating that the vascular bed of metastasis is a viable target site for nanoparticles.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.|Department of Radiology, Case Western Reserve University, Cleveland, Ohio.|Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Pubudu M
authors.initials: PM
authors.lastname: Peiris
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.|Department of Radiology, Case Western Reserve University, Cleveland, Ohio.|Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Partha
authors.initials: P
authors.lastname: Deb
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.|Department of Radiology, Case Western Reserve University, Cleveland, Ohio.|Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Doolittle
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.|Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Gilad
authors.initials: G
authors.lastname: Doron
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.|Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Amy
authors.initials: A
authors.lastname: Goldberg
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.|Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Priya
authors.initials: P
authors.lastname: Govender
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.|Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Shruti
authors.initials: S
authors.lastname: Shah
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.|Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Swetha
authors.initials: S
authors.lastname: Rao
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.|Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Sarah
authors.initials: S
authors.lastname: Carbone
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.|Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cotey
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.|Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Meilyn
authors.initials: M
authors.lastname: Sylvestre
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.|Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Sohaj
authors.initials: S
authors.lastname: Singh
authors.affiliation: Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio.
authors.forename: William P
authors.initials: WP
authors.lastname: Schiemann
authors.affiliation: Department of Radiology, Case Western Reserve University, Cleveland, Ohio.|Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio.|Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.|Department of Radiology, Case Western Reserve University, Cleveland, Ohio.|Case Center for Imaging Research, Case Western Reserve University, Cleveland, Ohio.|Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Karathanasis
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006046:Gold / Q000737:chemistry; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008024:Ligands; D008163:Luminescent Measurements; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism*; D011877:Radionuclide Imaging; D011994:Recombinant Proteins / Q000378:metabolism; D013499:Surface Properties; D013667:Technetium; D051598:Whole Body Imaging
chemical_list: D000970:Antineoplastic Agents; D039302:Integrin alphaVbeta3; D008024:Ligands; D008164:Luminescent Proteins; D010456:Peptides, Cyclic; D011994:Recombinant Proteins; C583418:cyclo(arginyl-glycyl-aspartyl-phenylalanyl-cysteinyl); D013667:Technetium; D006046:Gold
keywords: breast cancer micrometastasis; cancer; gold nanoparticle; nanoparticles; nuclear imaging; scintigraphy; site-specific delivery; targeted drug delivery; vascular targeting