Chemoradiotherapeutic Magnetic Nanoparticles for Targeted Treatment of Nonsmall Cell Lung Cancer.
Lung cancer is the leading cause of cancer-related death in the United States and approximately 85% of all lung cancers are classified as nonsmall cell (NSCLC). We here use an innovative approach that may ultimately allow for the clinician to target tumors and aggressively reduce tumor burden in patients with NSCLC. In this study, a platinum (Pt)-based chemotherapeutic (cisplatin, carboplatin, or oxaliplatin) and holmium-165 (Ho), which can be neutron-activated to produce the holmium-166 radionuclide, have been incorporated together in a garnet magnetic nanoparticle (HoIG-Pt) for selective delivery to tumors using an external magnet. The synthesized magnetic HoIG nanoparticles were characterized using PXRD, TEM, ICP-MS, and neutron-activation. Platinum(II) drugs were incorporated onto HoIG, and these were characterized using FTIR, EDX, ICP-MS, and zeta potential measurements, and in vitro and in vivo studies were performed using a HoIG-platinum system. Results indicate that neutron-activated (166)HoIG-cisplatin is more toxic toward NSCLC A549 cells than is blank (166)HoIG and free cisplatin, and that when an external magnetic field is applied in vivo, higher tumor to liver ratios of Ho are observed than when no magnet is applied, suggesting that magnetic targeting is achieved using this system. Furthermore, an efficacy study demonstrated the inhibition of tumor growth by chemoradiotherapeutic magnetic nanoparticles, compared to no treatment controls.
Department of Chemistry, University of Texas at Dallas , 800 West Campbell Road, Richardson, Texas 75080, United States.
Imalka
I
Munaweera
Depatment of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center , 3500 Camp Bowie Boulevard, Fort Worth, Texas 76107, United States.
Yi
Y
Shi
Depatment of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center , 3500 Camp Bowie Boulevard, Fort Worth, Texas 76107, United States.
Bhuvaneswari
B
Koneru
Texas Health Research and Education Institute , Plano, Texas 75093, United States.
Ruben
R
Saez
Department of Chemistry, University of Texas at Dallas , 800 West Campbell Road, Richardson, Texas 75080, United States.
Ali
A
Aliev
Depatment of Pharmaceutical Sciences, University of North Texas System College of Pharmacy, University of North Texas Health Science Center , 3500 Camp Bowie Boulevard, Fort Worth, Texas 76107, United States.
Anthony J
AJ
Di Pasqua
Department of Chemistry, University of Texas at Dallas , 800 West Campbell Road, Richardson, Texas 75080, United States.
Kenneth J
KJ
Balkus
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D045744:Cell Line, Tumor; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006695:Holmium / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011868:Radioisotopes / Q000008:administration & dosage / Q000627:therapeutic use
D000970:Antineoplastic Agents; D058185:Magnetite Nanoparticles; D011868:Radioisotopes; D002945:Cisplatin; D006695:Holmium
cancer; chemotherapy; magnetic nanoparticles; platinum drugs; radiotherapy