NIRT: Magnetically and Thermally Active Nanoparticles for Cancer Treatment (CBET-0609117)Carlos Rinaldi, Madeline Torres-Lugo, Gustavo Gutierrez, J. Zach Hilt, and Silvina Tomassone

0

0.2

0.4

0.6

0.8

1

1.2

DMEM 37 C 41 C 45 C 50 C

Via

bilit

y R

atio

Hyperthermia Caused by Hot Air

0

0.2

0.4

0.6

0.8

1

1.2

DMEM 1.18 2.36 7.09 11.81 Bleach1.5%

mg/mL

Via

bilit

y

hour 6 h 24

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

CH3

H2C CH

C O

HN

CH

H3C

=

=

+

NIPMAM

N

H3C CH2CH2O

O

-C-CH=CH2

+CH3

H2C C

C O

HN

CH

H3C

=

=

CH3

+

In presence of AIBN initiator and MBA*

+Free

polymerCH2O Si

OH

OH

CH2CH2O C

O=

C CH

CH3

CH2

Magnetite

MPS

CH2O Si

OH

OH

CH2CH2O C

O=

C=CH3

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

2 2

02 22 1

HP

From thermodynamic arguments, the cyclic energy dissipation rate per

unit volume is:

t t t b b b a

m

Tc k T w c T T

tQ P

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 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

Potential Advantages of Using Nanoparticles