Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer

• Published in: Biomaterials 2010-06, Vol.31 (18), p.4995-5006
• Main Authors: Maeng, Jin Hee, Lee, Don-Haeng, Jung, Kyung Hee, Bae, You-Han, Park, In-Suh, Jeong, Seok, Jeon, Yong-Sun, Shim, Chang-Koo, Kim, Wooyoung, Kim, Jungahn, Lee, Jeongmi, Lee, Yoon-Mi, Kim, Ji-Hee, Kim, Won-Hong, Hong, Soon-Sun
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - therapeutic use; Apoptosis - drug effects; Carrier Proteins - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Dentistry; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - therapeutic use; Drug delivery; Ferric Compounds - chemistry; Folate Receptors, GPI-Anchored; Humans; Liver cancer; Liver Neoplasms - diagnosis; Liver Neoplasms - drug therapy; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Magnetics; Male; Nanoparticles; Nanoparticles - chemistry; Rabbits; Rats; Rats, Sprague-Dawley; Receptors, Cell Surface - metabolism
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2010.02.068

Abstract To develop a drug delivery system with enhanced efficacy and minimized adverse effects, we synthesized a novel polymeric nanoparticles, (YCC-DOX) composed of poly (ethylene oxide)-trimellitic anhydride chloride-folate (PEO-TMA-FA), doxorubicin (DOX) and superparamagnetic iron oxide (Fe3 O4 ) and folate. The efficacy of the nanoparticles was evaluated in rats and rabbits with liver cancer, in comparison with free-DOX (FD) and a commercial liposome drug, DOXIL® . YCC-DOX showed the anticancer efficacy and specifically targeted folate receptor (FR)-expressing tumors, thereby increasing the bioavailability and efficacy of DOX. The relative tumor volume of the YCC-DOX group was decreased two- and four-fold compared with the FD and DOXIL® groups in the rat and rabbit models, respectively. Furthermore, YCC-DOX showed higher MRI sensitivity comparable to a conventional MRI contrast agent (Resovist® ), even in its lower iron content. In the immunohistochemical analysis, YCC-DOX group showed the lower expression of CD34 and Ki-67, markers of angiogenesis and cell proliferation, respectively, while apoptotic cells were significantly rich in the YCC-DOX group in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. These results indicate that YCC-DOX is a promising candidate for treating liver cancer and monitoring the progress of the cancer using MRI.