Hyperthermia Caused by Hot Air

1. NIRT: Magnetically and Thermally Active Nanoparticles for Cancer Treatment (CBET-0609117)Carlos Rinaldi, Madeline Torres-Lugo, Gustavo Gutierrez, J. Zach Hilt, and Silvina Tomassone CH3 MPS H2C CH H2C C = = C = O C = O OH O HN HN = = O CH2 C C CH2 CH2 Si O CH CH CH3 OH H3C H3C Magnetite Contraction of the copolymer structure Fluorescence intensity increases OH O Free polymer = Potential Advantages of Using Nanoparticles O CH2 C C CH CH2 CH2 Si O + Suspensions of Magnetic Nanoparticles for Cancer Treatment CH3 OH Energy Dissipation and Heat Transfer in Magnetic Fluid Hyperthermia Fluorescence Intensity as a Function of Temperature • Particle size 10-100 nm • Injectable • High circulation lifetime • Permeable through tumor leaky vasculature • Controllable surface charge (-5mV to +5mV) • Minimize phagocytosis • Avoid non-specific interactions with blood and tissues • Avoid aggregation • Functionalized nanoparticles may target specific cell types (cancerous vs healthy) • Minimize damage to surrounding healthy tissue • Fe3O4 nanoparticles are bio-absorbable • Inject and forget treatment • Targeted energy delivery at nanoscale • Uniform hyperthermia at the tumor site From thermodynamic arguments, the cyclic energy dissipation rate per unit volume is: Dependent on particle magnetic properties, concentration, size, polydispersity, and the viscous properties of the surrounding medium Large dissipation rates reported in adiabatic liquid suspension with 7% vol/vol particles Hydrodynamic Diameter as a Function of Temperature Heat transfer in the tissue may be modeled using Penne’s bio-heat equation: Heat generation is balanced by blood perfusion – this can dramatically affect actual temperature rise Variation of the fluorescence intensity versus temperature for 1% (w/v) of magnetite nanoparticles coated with fluorescent-PNIPAM in aqueous solution (crosslinking density 3.5 %, ex: 450 nm, em: 590 nm). Hydrodynamic diameter of magnetite nanoparticles coated with PNIPAM and Fluorescent-PNIPAM as a function of temperature (crosslinking density 3.5 %), obtained using Dynamic Light Scattering. A LCST of about 34 ºC was observed Fluorescent Thermoresponsive Magnetic Nanoparticles as “Nanothermometers” Free Radical Polymerization on Magnetite O -C-CH=CH2 H3C CH2CH2O Magnetite nanoparticles coated with acrylamide polymers such as PNIPAM and a fluorescent modified acrylamide (FMA) monomer can be used for biomedical applications as nano magnetic fluorescent-thermometers N + + + CH2 CH3 CH3 NIPAM NIPMAM Fluorescent Acrylamide Monomer In presence of AIBN initiator and MBA* Application of an AC magnetic field causes energy dissipation Free radical polymerization Magnetite nanoparticle At 60 C for 8 h Brush of fluorescent thermo-responsive polymer Brush of fluorescent thermo-responsive polymer *AIBN: ,’-Azoisobutyronitrile; MBA: Methyl bis-acrylamide MFH – 30 min in Caco-2 cells with autoclave ferrofluid (22.36 mg/mL) (Power = 100%, Volts =320 V, Frequency = 260 kHz, Current = 54 A) MFH – 0 h contact, 30 min in Caco-2 cells with autoclave ferrofluid (Power = 100%, Volts =320 V, Frequency = 260 kHz, Current = 54 A) Hyperthermia Caused by Hot Air Viability Analysis of Autoclave Commercial Ferrofuid (n=12±stdv) Magnetic nanoparticles inside cancer cell Magnetic nanoparticles The destruction of cancerous cells loaded with magnetic nanoparticles upon the application of an oscillating magnetic field is called magnetocytolysis Application of an AC magnetic field. Temperature rise to ~46°C (hyperthermia) Destruction of cancer cell