Near-infrared Resonant Multilayer Half-Shell Nanoparticles for Photothermally Controlled Drug Delivery and MRI Enhancement

Multifunctional Nanoparticles for
Photothermally Controlled Drug
Delivery and Magnetic Resonance
Imaging Enhancement
Kyung-Hwa Yoo
(Yonsei University)
Multifunctional Nanoparticle
Au layer
Drug
Photothermal
therapy
Photothermally
controlled drug
delivery
Biocompatible &
biodegradable polymer
Magnetic layer
MRI contrast agents
Au nanoshell
PLGA beads
O2 plasma
PMMA
PMMA
Si substrate
PS beads deposition
Si substrate
Au deposition
Lift-off
PMMA
Si substrate
Visible/NIR spectra
1.0
(b) PS
Absorbance (a.u.)
30 nm
20 nm
14 nm
15 nm
20 nm
25 nm
0.5
400
600
800
1000 1200
Wavelength (nm)
10 nm
400
600
800
1000 1200
W avelength (nm)
Hyperthermia
o
Temperature ( C)
46
PS-Au half-shell
44
42
40
PS nanoparticle
38
Au nanoparticle
Water
36
0
50
100
150
Time (s)
200
Hyperthermia
(a)
(b)
2
C=145 µg/ml
45
P=25 W/cm
45
2
P=25 W/cm
40
145 µg/mL
40
2
P=15 W/cm
35
72.5 µg/mL
35
36.25 µg/mL
2
P=7 W/cm
30
0
50
100
150
Time (s)
200
30
0
50
100
150
Time (s)
200
Photothermal toxicity (laser 15a)
Calcein-AM
Bright field image
Without particle
Laser
15a 50 min
With particle
incubation
(100ug/ml) 1 day
Laser
15a 15 min
50 min
Drug Release with & without NIR irradiation
(a)
100
Cumulative % Released
-1
slope = 18.059 day
80
60
-1
slope = 9.0738 day
40
with NIR irradiation
without NIR irradation
20
0
0
1
2
Time (day)
3
4
(b) With NIR illumination
0 min.
15 min.
50 min.
2 μm
2 μm
2 μm
0 min.
15 min.
50 min.
2 μm
2 μm
2 μm
(b) Without NIR illumination
TIRFM images
(a)
0 min.
10 min.
15 min.
50 min.
10 min.
15 min.
50 min.
300 nm
(b)
0 min.
300 nm
0 day
After 2-day NIR irradiation
After 3-day NIR irradiation
After 3 days without NIR irradiation
(b)
(a)
0.38
55
50
o
0.40
60
Temperature ( C)
0 day
1 day
2 day
3 day
7 day
Temperature (°C)
Absorbance (a.u.)
60
40
50
45
40
35
30
25
20
0
30
0.36
700
800
900
Wavelength (nm)
5
10
15
20
Time (min)
0
1
Time (min.)
2
3
(a)
(b)
Au
Mn
(c)
0.32
Mn (10 nm)/Au (25 nm)
0.28
1/T2 (1/sec.)
Absorbance (a.u.)
0.36
Mn(10 nm)/Au(25 nm) H-S NPs
Mn(0 nm)/Au(25 nm) H-S NPs
4
2
Mn (10 nm)/Au (0 nm)
400
600
800
1000
Wavelength (nm)
0
0.0
0.5
1.0
1.5
Relative nanoparticle concentration
Acknowlegement
Huiyul Park; Sungbaek Seo, Kyujung Kim
(Nanomedical Graduate Program)
Yang, Jae Moon; Haam, Seung Ju
(Dept. of Chemical Engineering)
Dong hyun Kim
(Depat. of Electrical and Electronic Engineering
Jinsuk Suh
(Dept. of Radiology)
* Funding: KOSEF through National Core Research
Center for Nanomedical Technology