RESUMO
Combining diagnosis and treatment approaches in one entity is the goal of theranostics for cancer therapy. Magnetic nanoparticles have been extensively used as contrast agents for nuclear magnetic resonance imaging as well as drug carriers and remote actuation agents. Poly(2-oxazoline)-based polymeric micelles, which have been shown to efficiently solubilize hydrophobic drugs and drug combinations, have high loading capacity (above 40% w/w) for paclitaxel. In this study, we report the development of novel theranostic system, NanoFerrogels, which is designed to capitalize on the magnetic nanoparticle properties as imaging agents and the poly(2-oxazoline)-based micelles as drug loading compartment. We developed six formulations with magnetic nanoparticle content of 0.3%-12% (w/w), with the z-average sizes of 85-130â¯nm and ξ-potential of 2.7-28.3â¯mV. The release profiles of paclitaxel from NanoFerrogels were notably dependent on the degree of dopamine grafting on poly(2-oxazoline)-based micelles. Paclitaxel loaded NanoFerrogels showed efficacy against three breast cancer lines which was comparable to free paclitaxel. They also showed improved tumor and lymph node accumulation and signal reduction in vivo (2.7% in tumor; 8.5% in lymph node) compared to clinically approved imaging agent ferumoxytol (FERAHEME®) 24â¯h after administration. NanoFerrogels responded to super-low frequency alternating current magnetic field (50 kA m-1, 50â¯Hz) which accelerated drug release from paclitaxel-loaded NanoFerrogels or caused death of cells loaded with NanoFerrogels. These proof-of-concept experiments demonstrate that NanoFerrogels have potential as remotely actuated theranostic platform for cancer diagnosis and treatment.
Assuntos
Antineoplásicos , Neoplasias da Mama , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Óxido Ferroso-Férrico , Humanos , Campos Magnéticos , Micelas , Oxazóis , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Medicina de PrecisãoRESUMO
We describe the time-resolved thermal changes in indocyanine green (ICG)-assisted diode laser ablation of dental caries as a potential technique for painless treatment based on the selective photoabsorption and controlled photothermal ablation. Static ablation mode produced a higher temperature rise compared with scanning mode due to localized accumulation of heat. A temperature rise between 45-80 and 70-95 °C was obtained after 20 s that corresponded to 29 and 80 W cm-2, respectively. The temperature of the tooth surface increased by irradiation time, and it behaved linearly up to 70 °C at 29 and 80 W cm-2. A maximum ablation per area of about 0.3 and 0.45 mg cm-2 was achieved after 80 s exposure at 29 and 80 W cm-2, respectively. A statistically significant difference is observed in mean carious teeth weight at various exposure times between low and high irradiances. A thermal penetration depth of 0.8-9 mm is determined for 1-100 s of exposure time. The IR thermal imaging of ICG temperature as a function of exposure time showed a linear increase for 60 s beyond which it deviated. The laser-induced fluorescence spectroscopy indicated that the ICG quality can be altered during the course of irradiation, which in our case, it corresponded to ≈ 78% loss of signal within 23 min of exposure. The caries removal experiment was performed within 100 s corresponding to ≈ 7% loss. We believe that the application of the above-combined technique can be utilized as a monitoring device to control the ablation interaction process.