Using targeted magnetic arsenic trioxide nanoparticles for osteosarcoma treatment.
The present study was to investigate the therapeutic efficacy of the magnetic arsenic trioxide (ATO) nanoparticles against osteosarcoma in vivo tumor models. ATO was incorporated in the magnetic nanoparticles and encapsulated by poly lactic acid. Human MG-63 osteosarcoma cells were injected subcutaneously into the nude mice. After 15 days, the mice were randomly assigned to the four groups (n=6 mice): group 1: control, saline only (10 mL kg(-1) day(-1), intravenously (i.v.)); group 2: ATO alone (5 mg kg(-1) day(-1), i.v.); group 3: magnetic ATO nanoparticles at a dose equivalent to 50% of the ATO alone, with an external magnetic field on the tumor; group 4: CDDP, cisplatin (5 mg kg(-1) day(-1), i.v.). The mice were sacrificed after 21 days. In vitro release profiles showed that ATO was released rapidly from the nanoparticles. The magnetic ATO evaluation indicated that the magnetic nanoparticles might localize under the magnet in vivo. The tumor volume examination showed that the treatment with magnetic ATO nanoparticles achieved the similar inhibition effect on osteosarcoma as that of CDDP or ATO alone. Electron microscopic features typical of apoptosis were identified in the tumor tissue with the three-drug treatment. This "magnetic ATO targeting" offers an opportunity to treat osteosarcoma with a lower dose.
Li
Xue-Song
XS
Department of Orthopedics, First Hospital of Harbin Medical University, Harbin, China. 19x9s9@126.com
Li
Wei-Qing
WQ
Wang
Wen-Bo
WB
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001682:Biological Availability; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods*; D005290:Ferric Compounds / Q000737:chemistry; D005296:Ferrous Compounds / Q000737:chemistry; D006801:Humans; D007668:Kidney / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry; D008280:Magnetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D010087:Oxides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010316:Particle Size; D011091:Polyesters; D011108:Polymers / Q000737:chemistry; D011817:Rabbits; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D001152:Arsenicals; D005290:Ferric Compounds; D005296:Ferrous Compounds; D010087:Oxides; D011091:Polyesters; D011108:Polymers; C000499:ferric oxide; D019344:Lactic Acid; C033616:poly(lactide); C034236:ferrous oxide; D002945:Cisplatin; D000077237:Arsenic Trioxide