title: Nanoparticles coated with the tumor-penetrating peptide iRGD reduce experimental breast cancer metastasis in the brain.
abstract: Metastasis is the main killer in cancer; consequently, there is great interest in novel approaches to prevent and treat metastatic disease. Brain metastases are particularly deadly, as the protection of the blood-brain barrier obstructs the passage of common anticancer drugs. This study used magnetic resonance imaging (MRI) to investigate the therapeutic effects of nanoparticles coated with a tumor-penetrating peptide (iRGD) against a preclinical model of breast cancer brain metastasis. Single doses of iRGD nanoparticle were administered intravenously, and the effect on tumor growth was observed over time. iRGD nanoparticles, when applied in the early stages of metastasis development, strongly inhibited tumor progression. Overall, this study demonstrated for the first time that a single dose of iRGD nanoparticle can have a significant effect on metastatic tumor progression and nonproliferative cancer cell retention when applied early in course of tumor development. These data suggest that iRGD nanoparticles may be useful in preventatively reducing metastasis after a cancer diagnosis has been established.
  
  
  CONCLUSIONS
  bSSFP MRI can be used to track nonproliferative iron-labeled cells and tumor development over time. iRGD-NW, when applied early, has a significant effect on metastatic tumor progression. Retained signal voids represent a subpopulation of nonproliferating tumor cells. Reduced cell retention and tumor burden show a role for iRGD-NW in metastasis prevention. iRGD target is universally expressed; thus, iRGD-NW should be clinically translatable.
authors: Robarts Research Institute, University of Western Ontario, 1151 Richmond St N, London, ON, N6A 5B7, Canada. hamilton@robarts.ca.
authors: Amanda M
authors: AM
authors: Hamilton
authors: Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
authors: Sallouha
authors: S
authors: Aidoudi-Ahmed
authors: Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
authors: Shweta
authors: S
authors: Sharma
authors: Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
authors: Venkata R
authors: VR
authors: Kotamraju
authors: Robarts Research Institute, University of Western Ontario, 1151 Richmond St N, London, ON, N6A 5B7, Canada.
authors: Paula J
authors: PJ
authors: Foster
authors: Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
authors: Kazuki N
authors: KN
authors: Sugahara
authors: Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.|Center for Nanomedicine and Department of Cell, Molecular and Developmental Biology, University of California, Santa Barbara, CA, USA.
authors: Erkki
authors: E
authors: Ruoslahti
authors: Radiological Sciences Laboratory, Stanford University School of Medicine, Stanford, CA, USA.
authors: Brian K
authors: BK
authors: Rutt
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000473:pathology / Q000556:secondary*; D001943:Breast Neoplasms / Q000150:complications* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009842:Oligopeptides / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; C569656:N-end cysteine peptide tumor-homing peptide; D009842:Oligopeptides
keywords: Brain metastasis; Cell tracking; Magnetic resonance imaging; Nanoparticle; Tumor growth inhibition; iRGD