Transcript Slide 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
Suspensions of Magnetic Nanoparticles
for Cancer Treatment
Potential Advantages of Using Nanoparticles
• 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
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
Free Radical Polymerization on
Magnetite
Fluorescent Thermoresponsive Magnetic
Nanoparticles as “Nanothermometers”
CH3
H2C = C
MPS
H2C = CH
OH
C=O
=
O
O Si CH2CH2CH2O C C= CH2
+
CH3
OH
Magnetite
HN
HN
+
CH CH3
of the surrounding medium
0 H  
2 1   2 2 
2
Large dissipation rates reported in
adiabatic liquid suspension with 7%
vol/vol particles
Heat transfer in the tissue may be
modeled using Penne’s bio-heat
equation:
T
t ct
    kt T   wb b cb Ta  T 
t
Qm  P
Heat generation is balanced
by blood perfusion – this can
dramatically affect actual
temperature rise
Fluorescence Intensity as a Function of
Temperature
Hydrodynamic Diameter as a Function of
Temperature
N
+
CH CH3
H3C
H3C
NIPAM
Free radical
polymerization
NIPMAM
Fluorescent Acrylamide
Monomer
OH
=
O
O Si CH2CH2CH2O C C CH
At 60 C for 8 h
Brush of fluorescent thermo-responsive polymer
+
Free
polymer
OH
Brush of fluorescent thermoresponsive polymer
Viability Analysis of Autoclave
Commercial Ferrofuid (n=12±stdv)
hour 6
1.2
1.2
1
1
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.
CH3
*AIBN: ,’-Azoisobutyronitrile; MBA: Methyl bis-acrylamide
Hyperthermia Caused by Hot Air
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).
A LCST of about 34 ºC was observed
MFH – 0 h contact, 30 min in Caco-2 cells
with autoclave ferrofluid
(Power
=
100%,
Volts
=320
V,
Frequency
1.2
= 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)
0h, 0h
1
h 24
0h, 4h
4h, 0h
0.8
0.8
0.6
0.6
0.8
1
0.6
0.8
Viability Ratio
Viability Ratio
1.2
Viability
Viability Ratio
P
2
In presence of AIBN initiator and MBA*
Application of an AC
magnetic field causes
energy dissipation
Magnetite nanoparticle
From thermodynamic arguments, the
Dependent on particle magnetic
properties, concentration, size,
cyclic energy dissipation rate per
polydispersity, and the viscous properties
unit volume is:
C=O
Contraction of the
copolymer structure
Fluorescence
intensity increases
O
CH2CH2O -C-CH=CH2
H3C
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
fluorescentthermometers
Energy Dissipation and Heat Transfer in
Magnetic Fluid Hyperthermia
0.4
0.4
0.4
0.2
0.4
0.2
0.2
0.6
0.2
0
0
0
DMEM
37 C
41 C
45 C
50 C
DMEM
1.18
2.36
7.09
mg/mL
11.81
Bleach
1.5%
DMEM
2.236
mg mL
Without magnetic field
6.703
mg mL
11.18
mg mL
Corner of the plate with magnetic field
15.652
mg mL
22.36
1.5%
mg mL NaOCL
Center of the plate with magnetic field
0
DMEM/Incubator
Campo Esquina
Campo Centro
1.5% NaOCL