NIRT: Magnetically and Thermally Active Nanoparticles for Cancer Treatment (CBET ) Carlos Rinaldi, Madeline Torres-Lugo, Gustavo Gutierrez, J. Zach Hilt, and Silvina Tomassone Hyperthermia Caused by Hot Air Viability Analysis of Autoclave Commercial Ferrofuid (n=12±stdv) MFH – 0 h contact, 30 min in Caco-2 cells with autoclave ferrofluid (Power = 100%, Volts =320 V, Frequency = 260 kHz, Current = 54 A) 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) Free Radical Polymerization on Magnetite Free radical polymerization At 60  C for 8 h Brush of fluorescent thermo- responsive polymer *AIBN: ,  ’-Azoisobutyronitrile; MBA: Methyl bis-acrylamide NIPAM CH 3 H2CH2CCH CO HN CH H3CH3C = = + NIPMAM N H3CH3CCH 2 CH 2 O O -C-CH = CH 2 + CH 3 H2CH2CC CO HN CH H3CH3C = = CH 3 + In presence of AIBN initiator and MBA* + Free polymer CH 2 O Si OH CH 2 O C O = C CH CH 3 CH 2 Magnetite MPS CH 2 O Si OH CH 2 O C O = C = CH 3 Fluorescent Acrylamide Monomer Fluorescent Thermoresponsive Magnetic Nanoparticles as “Nanothermometers” 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 Brush of fluorescent thermo-responsive polymer Magnetite nanoparticle Application of an AC magnetic field causes energy dissipation Contraction of the copolymer structure Fluorescence intensity increases 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 Hydrodynamic Diameter as a Function of Temperature Fluorescence Intensity as a Function of Temperature 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). The destruction of cancerous cells loaded with magnetic nanoparticles upon the application of an oscillating magnetic field is called magnetocytolysis Magnetic nanoparticles Magnetic nanoparticles inside cancer cell Application of an AC magnetic field. Temperature rise to ~46°C (hyperthermia) Destruction of cancer cell Suspensions of Magnetic Nanoparticles for Cancer Treatment Energy Dissipation and Heat Transfer in Magnetic Fluid Hyperthermia From thermodynamic arguments, the cyclic energy dissipation rate per unit volume is: Heat transfer in the tissue may be modeled using Penne’s bio-heat equation: 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 Heat generation is balanced by blood perfusion – this can dramatically affect actual temperature rise Particle size 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 Fe 3 O 4 nanoparticles are bio-absorbable –Inject and forget treatment Targeted energy delivery at nanoscale –Uniform hyperthermia at the tumor site Potential Advantages of Using Nanoparticles