title: Vascular targeted nanoparticles for imaging and treatment of brain tumors.
abstract: OBJECTIVE
  Development of new therapeutic drug delivery systems is an area of significant research interest. The ability to directly target a therapeutic agent to a tumor site would minimize systemic drug exposure, thus providing the potential for increasing the therapeutic index.
  
  
  METHODS
  Photodynamic therapy (PDT) involves the uptake of a sensitizer by the cancer cells followed by photoirradiation to activate the sensitizer. PDT using Photofrin has certain disadvantages that include prolonged cutaneous photosensitization. Delivery of nanoparticles encapsulated with photodynamic agent specifically to a tumor site could potentially overcome the drawbacks of systemic therapy. In this study, we have developed a multifunctional polymeric nanoparticle consisting of a surface-localized tumor vasculature targeting F3 peptide and encapsulated PDT and imaging agents.
  
  
  RESULTS
  The nanoparticles specifically bound to the surface of MDA-435 cells in vitro and were internalized conferring photosensitivity to the cells. Significant magnetic resonance imaging contrast enhancement was achieved in i.c. rat 9L gliomas following i.v. nanoparticle administration. Serial magnetic resonance imaging was used for determination of pharmacokinetics and distribution of nanoparticles within the tumor. Treatment of glioma-bearing rats with targeted nanoparticles followed by PDT showed a significant improvement in survival rate when compared with animals who received PDT after administration of nontargeted nanoparticles or systemic Photofrin.
  
  
  CONCLUSIONS
  This study reveals the versatility and efficacy of the multifunctional nanoparticle for the targeted detection and treatment of cancer.
authors.affiliation: Molecular Therapeutics, Inc., Ann Arbor, MI 48109, USA.
authors.forename: G Ramachandra
authors.initials: GR
authors.lastname: Reddy
authors.forename: Mahaveer S
authors.initials: MS
authors.lastname: Bhojani
authors.forename: Patrick
authors.initials: P
authors.lastname: McConville
authors.forename: Jonathan
authors.initials: J
authors.lastname: Moody
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Moffat
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Hall
authors.forename: Gwangseong
authors.initials: G
authors.lastname: Kim
authors.forename: Yong-Eun L
authors.initials: YE
authors.lastname: Koo
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Woolliscroft
authors.forename: James V
authors.initials: JV
authors.lastname: Sugai
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Johnson
authors.forename: Martin A
authors.initials: MA
authors.lastname: Philbert
authors.forename: Raoul
authors.initials: R
authors.lastname: Kopelman
authors.forename: Alnawaz
authors.initials: A
authors.lastname: Rehemtulla
authors.forename: Brian D
authors.initials: BD
authors.lastname: Ross
mesh_terms: D000792:Angiography / Q000379:methods; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D001932:Brain Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000401:mortality / Q000628:therapy*; D003952:Diagnostic Imaging / Q000379:methods; D017323:Dihematoporphyrin Ether / Q000008:administration & dosage; D004333:Drug Administration Routes; D004337:Drug Carriers / Q000627:therapeutic use; D005290:Ferric Compounds / Q000008:administration & dosage; D005910:Glioma / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000627:therapeutic use*; D036103:Nanotechnology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D051381:Rats; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
chemical_list: D004337:Drug Carriers; D005290:Ferric Compounds; D017319:Photosensitizing Agents; C000499:ferric oxide; D017323:Dihematoporphyrin Ether