Targeted sonodynamic therapy using protein-modified TiO2 nanoparticles.
Our previous study suggested new sonodynamic therapy for cancer cells based on the delivery of titanium dioxide (TiO(2)) nanoparticles (NPs) modified with a protein specifically recognizing target cells and subsequent generation of hydroxyl radicals from TiO(2) NPs activated by external ultrasound irradiation (called TiO(2)/US treatment). The present study first examined the uptake behavior of TiO(2) NPs modified with pre-S1/S2 (model protein-recognizing hepatocytes) by HepG2 cells for 24h. It took 6h for sufficient uptake of the TiO(2) NPs by the cells. Next, the effect of the TiO(2)/US treatment on HepG2 cell growth was examined for 96 h after the 1 MHz ultrasound was irradiated (0.1 W/cm(2), 30s) to the cells which incorporated the TiO(2) NPs. Apoptosis was observed at 6h after the TiO(2)/US treatment. Although no apparent cell-injury was observed until 24h after the treatment, the viable cell concentration had deteriorated to 46% of the control at 96 h. Finally, the TiO(2)/US treatment was applied to a mouse xenograft model. The pre-S1/S2-immobilized TiO(2) (0.1mg) was directly injected into tumors, followed by 1 MHz ultrasound irradiation at 1.0 W/cm(2) for 60s. As a result of the treatment repeated five times within 13 days, tumor growth could be hampered up to 28 days compared with the control conditions.
Institute of Nature and Environmental Technology, Kanazawa University, Kanazawa 920-1192, Japan. franco.ferrero@polito.it
Kazuaki
K
Ninomiya
Chiaki
C
Ogino
Shuhei
S
Oshima
Shiro
S
Sonoke
Shun-ichi
S
Kuroda
Nobuaki
N
Shimizu
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods; D053672:Electrochemotherapy / Q000379:methods*; D056945:Hep G2 Cells; D019220:High-Energy Shock Waves; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000473:pathology* / Q000628:therapy*; D011506:Proteins / Q000627:therapeutic use*; D011829:Radiation Dosage; D013010:Sonication / Q000379:methods*; D014025:Titanium / Q000528:radiation effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000379:methods*
D011506:Proteins; C009495:titanium dioxide; D014025:Titanium