Photothermal therapy (PTT) has been emerging as an effective, minimally invasive approach to treat cancers. However, a method to quantitatively evaluate the treatment effect after laser-induced thermotherapy (LITT) is needed. In this study, we used 808 nm laser radiation with three different power densities to treat the breast cancer tissue from 4T1 cell lines in a mouse model. The viscoelastic properties of the treated cancer tissues were characterized by a two-term Prony series using a ramp-hold indentation method. We observed that instantaneous shear modulus G0 was significantly higher for the treated cancer tissues than that of the untreated tissue when treated with a power density of 1.5 W/cm2, but significantly lower with a power density of 2.5 W/cm2. The long-term shear modulus G was also significantly higher for the cancer tissue at 1.5 W/cm2, compared to the untreated tissue. The treatment effects were verified by estimating the cell apoptosis rate using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Our results indicate that the viscoelastic properties of the tissue could potentially be used as biomarkers for evaluating the LITT treatment effect. In addition, we also observed a strain-independent behavior of the treated cancer tissue, which provided useful information for applying in vivo imaging method such as magnetic resonance elastography (MRE) for treatment evaluation based on biomechanical properties.

References

1.
Siegel
,
R. L.
,
Miller
,
K. D.
, and
Jemal
,
A.
,
2016
, “
Cancer Statistics, 2016
,”
Ca: Cancer J. Clin.
,
66
(
1
), pp.
7
30
.
2.
Lu
,
W. L.
,
Li
,
H. X.
,
Qian
,
B. Y.
,
Wang
,
Y.
,
Jansen
,
L.
,
Huang
,
G. W.
,
Tang
,
N. J.
,
Sun
,
Z.
,
Chen
,
K. X.
, and
De Bock
,
G. H.
,
2010
, “
The Clinical Characteristics and Prognosis of Chinese Early Stage Breast Cancer Patients: A Retrospective Study
,”
Breast J.
,
16
(
3
), pp.
331
333
.
3.
Brewster
,
A. M.
,
Chavez-MacGregor
,
M.
, and
Brown
,
P.
,
2014
, “
Epidemiology, Biology, and Treatment of Triple-Negative Breast Cancer in Women of African Ancestry
,”
Lancet Oncol.
,
15
(
13
), pp.
e625
e634
.
4.
Sun
,
C.
,
Wen
,
L.
,
Zeng
,
J.
,
Wang
,
Y.
,
Sun
,
Q.
,
Deng
,
L.
,
Zhao
,
C.
, and
Li
,
Z.
,
2016
, “
One-Pot Solventless Preparation of PEGylated Black Phosphorus Nanoparticles for Photoacoustic Imaging and Photothermal Therapy of Cancer
,”
Biomaterials
,
91
, pp.
81
89
.
5.
Kennedy
,
L. C.
,
Bickford
,
L. R.
,
Lewinski
,
N. A.
,
Coughlin
,
A. J.
,
Hu
,
Y.
,
Day
,
E. S.
,
West
,
J. L.
, and
Drezek
,
R. A.
,
2011
, “
A New Era for Cancer Treatment: Gold-Nanoparticle-Mediated Thermal Therapies
,”
Small
,
7
(
2
), pp.
169
183
.
6.
Mou
,
J.
,
Li
,
P.
,
Liu
,
C.
,
Xu
,
H.
,
Song
,
L.
,
Wang
,
J.
,
Zhang
,
K.
,
Chen
,
Y.
,
Shi
,
J.
, and
Chen
,
H.
,
2015
, “
Ultrasmall Cu2-x S Nanodots for Highly Efficient Photoacoustic Imaging-Guided Photothermal Therapy
,”
Small
,
11
(
19
), pp.
2275
2283
.
7.
Liang
,
C.
,
Diao
,
S.
,
Wang
,
C.
,
Gong
,
H.
,
Liu
,
T.
,
Hong
,
G.
,
Shi
,
X.
,
Dai
,
H.
, and
Liu
,
Z.
,
2014
, “
Tumor Metastasis Inhibition by Imaging-Guided Photothermal Therapy With Single-Walled Carbon Nanotubes
,”
Adv. Mater.
,
26
(
32
), pp.
5646
5652
.
8.
Zeng
,
J.
,
Cheng
,
M.
,
Wang
,
Y.
,
Wen
,
L.
,
Chen
,
L.
,
Li
,
Z.
,
Wu
,
Y.
,
Gao
,
M.
, and
Chai
,
Z.
,
2016
, “
pH-Responsive Fe(III)-Gallic Acid Nanoparticles for In Vivo Photoacoustic-Imaging-Guided Photothermal Therapy
,”
Adv. Healthcare Mater.
,
5
(
7
), pp.
772
780
.
9.
Su
,
X.
,
Fu
,
B.
, and
Yuan
,
J.
,
2017
, “
Gold Nanocluster-Coated Gold Nanorods for Simultaneously Enhanced Photothermal Performance and Stability
,”
Mater. Lett.
,
188
, pp.
111
114
.
10.
Yong
,
Y.
,
Cheng
,
X.
,
Bao
,
T.
, and
Zhao
,
Y.
,
2015
, “
Tungsten Sulfide Quantum Dots as Multifunctional Nanotheranostics for In Vivo Dual-Modal Image-Guided Photothermal/Radiotherapy Synergistic Therapy
,”
ACS Nano
,
9
(
12
), pp.
12451
12463
.
11.
Li
,
Z.
,
Wang
,
H.
,
Chen
,
Y.
,
Wang
,
Y.
,
Li
,
H.
,
Han
,
H.
,
Chen
,
T.
,
Jin
,
Q.
, and
Ji
,
J.
,
2016
, “
pH- and NIR Light-Responsive Polymeric Prodrug Micelles for Hyperthermia-Assisted Site-Specific Chemotherapy to Reverse Drug Resistance in Cancer Treatment
,”
Small
,
12
(
20
), pp.
2731
2740
.
12.
Eisenhauer
,
E. A.
,
Therasse
,
P.
,
Bogaerts
,
J.
,
Schwartz
,
L. H.
,
Sargent
,
D.
,
Ford
,
R.
,
Dancey
,
J.
,
Arbuck
,
S.
,
Gwyther
,
S.
,
Mooney
,
M.
,
Rubinstein
,
L.
,
Shankar
,
L.
,
Dodd
,
L.
,
Kaplan
,
R.
,
Lacombe
,
D.
, and
Verweij
,
J.
,
2009
, “
New Response Evaluation Criteria in Solid Tumours: Revised RECIST Guideline (Version 1.1)
,”
Eur. J. Cancer
,
45
(
2
), pp.
228
247
.
13.
Li
,
X.
,
Ferrel
,
G. L.
,
Guerra
,
M. C.
,
Hode
,
T.
,
Lunn
,
J. A.
,
Adalsteinsson
,
O.
,
Nordquist
,
R. E.
,
Liu
,
H.
, and
Chen
,
W. R.
,
2011
, “
Preliminary Safety and Efficacy Results of Laser Immunotherapy for the Treatment of Metastatic Breast Cancer Patients
,”
Photochem. Photobiol. Sci.
,
10
(
5
), pp.
817
821
.
14.
Tokes
,
T.
,
Kajary
,
K.
,
Szentmartoni
,
G.
,
Lengyel
,
Z.
,
Gyorke
,
T.
,
Torgyik
,
L.
,
Somlai
,
K.
,
Tokes
,
A. M.
,
Kulka
,
J.
, and
Dank
,
M.
,
2017
, “
Predictive and Prognostic Value of FDG-PET/CT Imaging and Different Response Evaluation Criteria After Primary Systemic Therapy of Breast Cancer
,”
Breast Cancer
,
24
(
1
), pp.
137
146
.
15.
Martin
,
A. C. B. M.
,
Fuzer
,
A. M.
, and
Becceneri
,
A. B.
,
2017
, “
[10]-Gingerol Induces Apoptosis and Inhibits Metastatic Dissemination of Triple Negative Breast Cancer In Vivo
,”
Oncotarget
,
8
(
42
), pp.
72260
72271
.
16.
Shintia
,
C.
,
Endang
,
H.
, and
Diani
,
K.
,
2016
, “
Assessment of Pathological Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Using the Miller-Payne System and TUNEL
,”
Malays. J. Pathol.
,
38
(
1
), pp.
25
32
http://www.mjpath.org.my/2016/v38n1/neoadjuvant-chemotherapy.pdf.
17.
Suresh
,
S.
,
Spatz
,
J.
,
Mills
,
J. P.
,
Micoulet
,
A.
,
Dao
,
M.
,
Lim
,
C. T.
,
Beil
,
M.
, and
Seufferlein
,
T.
,
2005
, “
Connections Between Single-Cell Biomechanics and Human Disease States: Gastrointestinal Cancer and Malaria
,”
Acta Biomater.
,
1
(
1
), pp.
15
30
.
18.
Suresh
,
S.
,
2007
, “
Biomechanics and Biophysics of Cancer Cells
,”
Acta Biomater.
,
3
(
4
), pp.
413
438
.
19.
Genin
,
G. M.
,
Shenoy
,
V. B.
,
Peng
,
G. C. Y.
, and
Buehler
,
M. J.
,
2017
, “
Integrated Multiscale Biomaterials Experiment and Modeling
,”
ACS Biomater. Sci. Eng.
,
3
(
11
), pp.
2628
2632
.
20.
Madani
,
N.
, and
Mojra
,
A.
,
2017
, “
Quantitative Diagnosis of Breast Tumors by Characterization of Viscoelastic Behavior of Healthy Breast Tissue
,”
J. Mech. Behav. Biomed.
,
68
, pp.
180
187
.
21.
Ramião
,
N. G.
,
Martins
,
P. S.
,
Rynkevic
,
R.
,
Fernandes
,
A. A.
,
Barroso
,
M.
, and
Santos
,
D. C.
,
2016
, “
Biomechanical Properties of Breast Tissue, a State-of-the-Art Review
,”
Biomech. Model. Mechanobiol.
,
15
(
5
), pp.
1307
1323
.
22.
Samani
,
A.
,
Bishop
,
J.
,
Luginbuhl
,
C.
, and
Plewes
,
D. B.
,
2003
, “
Measuring the Elastic Modulus of Ex Vivo Small Tissue Samples
,”
Phys. Med. Biol.
,
48
(
14
), pp.
2183
2198
.
23.
Samani
,
A.
,
Zubovits
,
J.
, and
Plewes
,
D.
,
2007
, “
Elastic Moduli of Normal and Pathological Human Breast Tissues: An Inversion-Technique-Based Investigation of 169 Samples
,”
Phys. Med. Biol.
,
52
(
6
), pp.
1565
1576
.
24.
Krouskop
,
T. A.
,
Wheeler
,
T. M.
,
Kallel
,
F.
,
Garra
,
B. S.
, and
Hall
,
T.
,
1998
, “
Elastic Moduli of Breast and Prostate Tissues Under Compression
,”
Ultrason. Imaging
,
20
(
4
), pp.
260
274
.
25.
Mojra
,
A.
,
Najarian
,
S.
,
Kashani
,
S. M. T.
, and
Panahi
,
F.
,
2012
, “
A Novel Tactile-Guided Detection and Three-Dimensional Localization of Clinically Significant Breast Masses
,”
J. Med. Eng. Technol.
,
36
(
1
), pp.
8
16
.
26.
Mojra
,
A.
,
Najarian
,
S.
,
Towliat Kashani
,
S. M.
,
Panahi
,
F.
, and
Yaghmaei
,
M.
,
2011
, “
A Novel Haptic Robotic Viscogram for Characterizing the Viscoelastic Behaviour of Breast Tissue in Clinical Examinations
,”
Int. J. Med. Rob.
,
7
(
3
), pp.
282
292
.
27.
Mariappan
,
Y. K.
,
Glaser
,
K. J.
,
Manduca
,
A.
,
Romano
,
A. J.
,
Venkatesh
,
S. K.
,
Yin
,
M.
, and
Ehman
,
R. L.
,
2009
, “
High-Frequency Mode Conversion Technique for Stiff Lesion Detection With Magnetic Resonance Elastography (MRE)
,”
Magn. Reson. Med.
,
62
(
6
), pp.
1457
1465
.
28.
Sinkus
,
R.
,
Tanter
,
M.
,
Xydeas
,
T.
,
Catheline
,
S.
,
Bercoff
,
J.
, and
Fink
,
M.
,
2005
, “
Viscoelastic Shear Properties of In Vivo Breast Lesions Measured by MR Elastography
,”
Magn. Reson. Imaging
,
23
(
2
), pp.
159
165
.
29.
Chang
,
J. M.
,
Won
,
J.-K.
,
Lee
,
K.-B.
,
Park
,
I. A.
,
Yi
,
A.
, and
Moon
,
W. K.
,
2013
, “
Comparison of Shear-Wave and Strain Ultrasound Elastography in the Differentiation of Benign and Malignant Breast Lesions
,”
Am. J. Roentgenol.
,
201
(
2
), pp.
W347
W356
.
30.
Coussot
,
C.
,
Kalyanam
,
S.
,
Yapp
,
R.
, and
Insana
,
M. F.
,
2009
, “
Fractional Derivative Models for Ultrasonic Characterization of Polymer and Breast Tissue Viscoelasticity
,”
IEEE Trans. Ultrason. Ferroelectr. Freq. Control
,
56
(
4
), pp.
715
726
.
31.
Ophir
,
J.
,
Garra
,
B.
,
Kallel
,
F.
,
Konofagou
,
E.
,
Krouskop
,
T.
,
Righetti
,
R.
, and
Varghese
,
T.
,
2000
, “
Elastographic Imaging
,”
Ultrasound Med. Biol.
,
26
(
Suppl. 1
), pp.
S23
S29
.
32.
Han
,
Y.
,
Wang
,
S.
,
Hibshoosh
,
H.
,
Taback
,
B.
, and
Konofagou
,
E.
,
2016
, “
Tumor Characterization and Treatment Monitoring of Postsurgical Human Breast Specimens Using Harmonic Motion Imaging (HMI)
,”
Breast Cancer Res.
,
18
(
1
), p.
46
.
33.
Feng
,
Y.
,
Lee
,
C.-H.
,
Sun
,
L.
,
Ji
,
S.
, and
Zhao
,
X.
,
2017
, “
Characterizing White Matter Tissue in Large Strain Via Asymmetric Indentation and Inverse Finite Element Modeling
,”
J. Mech. Behav. Biomed.
,
65
, pp.
490
501
.
34.
Feng
,
Y.
,
Gao
,
Y.
,
Wang
,
T.
,
Tao
,
L.
,
Qiu
,
S.
, and
Zhao
,
X.
,
2017
, “
A Longitudinal Study of the Mechanical Properties of Injured Brain Tissue in a Mouse Model
,”
J. Mech. Behav. Biomed.
,
71
, pp.
407
415
.
35.
Feng
,
Y.
,
Okamoto
,
R. J.
,
Namani
,
R.
,
Genin
,
G. M.
, and
Bayly
,
P. V.
,
2013
, “
Measurements of Mechanical Anisotropy in Brain Tissue and Implications for Transversely Isotropic Material Models of White Matter
,”
J. Mech. Behav. Biomed.
,
23
, pp.
117
132
.
36.
Qiu
,
S.
,
Zhao
,
X.
,
Chen
,
J.
,
Zeng
,
J.
,
Chen
,
S.
,
Chen
,
L.
,
Meng
,
Y.
,
Liu
,
B.
,
Shan
,
H.
,
Gao
,
M.
, and
Feng
,
Y.
,
2018
, “
Characterizing Viscoelastic Properties of Breast Cancer Tissue From 4T1 and SKBR3 Cell Lines With Indentation Using a Mouse Model
,”
J. Biomech.
,
69
, pp.
81
89
.
37.
Joseph
,
J. O. H.
, and
Samani
,
A.
,
2009
, “
Measurement of the Hyperelastic Properties of 44 Pathological Ex Vivo Breast Tissue Samples
,”
Phys. Med. Biol.
,
54
(
8
), pp.
2557
2569
.
38.
Plodinec
,
M.
,
Loparic
,
M.
,
Monnier
,
C. A.
,
Obermann
,
E. C.
,
Zanetti-Dallenbach
,
R.
,
Oertle
,
P.
,
Hyotyla
,
J. T.
,
Aebi
,
U.
,
Bentires-Alj
,
M.
, and
Lim
,
R. Y.
,
2012
, “
The Nanomechanical Signature of Breast Cancer
,”
Nat. Nanotechnol.
,
7
(
11
), pp.
757
765
.
39.
Umemoto
,
T.
,
Ueno
,
E.
,
Matsumura
,
T.
,
Yamakawa
,
M.
,
Bando
,
H.
,
Mitake
,
T.
, and
Shiina
,
T.
,
2014
, “
Ex Vivo and In Vivo Assessment of the Non-Linearity of Elasticity Properties of Breast Tissues for Quantitative Strain Elastography
,”
Ultrasound Med. Biol.
,
40
(
8
), pp.
1755
1768
.
40.
Griesenauer
,
R. H.
,
Weis
,
J. A.
,
Arlinghaus
,
L. R.
,
Meszoely
,
I. M.
, and
Miga
,
M. I.
,
2017
, “
Breast Tissue Stiffness Estimation for Surgical Guidance Using Gravity-Induced Excitation
,”
Phys. Med. Biol.
,
62
(
12
), pp.
4756
4776
.
41.
Feng
,
Y.
,
Okamoto
,
R. J.
,
Genin
,
G. M.
, and
Bayly
,
P. V.
,
2016
, “
On the Accuracy and Fitting of Transversely Isotropic Material Models
,”
J. Mech. Behav. Biomed.
,
61
, pp.
554
566
.
42.
Jing
,
H.
,
Cheng
,
W.
,
Li
,
Z. Y.
,
Ying
,
L.
,
Wang
,
Q. C.
,
Wu
,
T.
, and
Tian
,
J. W.
,
2016
, “
Early Evaluation of Relative Changes in Tumor Stiffness by Shear Wave Elastography Predicts the Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer
,”
J. Ultrasound Med.
,
35
(
8
), pp.
1619
1627
.
43.
Collins
,
C.
,
Osborne
,
L. D.
,
Guilluy
,
C.
,
Chen
,
Z.
,
O'Brien
,
E. T.
, III,
Reader
,
J. S.
,
Burridge
,
K.
,
Superfine
,
R.
, and
Tzima
,
E.
,
2014
, “
Haemodynamic and Extracellular Matrix Cues Regulate the Mechanical Phenotype and Stiffness of Aortic Endothelial Cells
,”
Nat. Commun.
,
5
(
1
), p.
3984
.
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