Vascular targeted nanoparticles for imaging and treatment of brain tumors.
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.
Reddy
G Ramachandra
GR
Molecular Therapeutics, Inc., Ann Arbor, MI 48109, USA.
Bhojani
Mahaveer S
MS
McConville
Patrick
P
Moody
Jonathan
J
Moffat
Bradford A
BA
Hall
Daniel E
DE
Kim
Gwangseong
G
Koo
Yong-Eun L
YE
Woolliscroft
Michael J
MJ
Sugai
James V
JV
Johnson
Timothy D
TD
Philbert
Martin A
MA
Kopelman
Raoul
R
Rehemtulla
Alnawaz
A
Ross
Brian D
BD
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
D004337:Drug Carriers; D005290:Ferric Compounds; D017319:Photosensitizing Agents; C000499:ferric oxide; D017323:Dihematoporphyrin Ether