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Name (Title):
Yukio NAGASAKI (Professor)
Affiliation:
International Center for Materials Nanoarchitectonics Satellite (MANA),
National Institute for Materials Science (NIMS) and Tsukuba Research
Center for Interdisciplinary Materials Science(TIMS), University of Tsukuba
Address:
Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
Email: Nagasaki@nagalabo.jp
Home Page: http://www.ims.tsukuba.ac.jp/~nagasaki_lab/index.htm
Presentation Title:
Nano-particle Assisted Therapy
Abstract:
Nanosized polymeric particles have versatile utilities such as carrier for drug delivery,
bioimaging and nano-diagnostic system. Recently, we have been focusing on preparation of
core-shell type polymeric nanogels, which possess crosslinked polyamine core and biocompatible
poly(ethylene glycol) (PEG) shell. The obtained nanogel showed volume phase transition in a
minute change in environmental pH. Using the nanogel thus prepared as a nanoreactor, new
nanomaterials were prepared for new therapy and imaging tools.
Recently, we have found that gold nanoparticles (GNPs) were successfully synthesized
through the self-reduction of Au(III) ions with PEGylated nanogels composed of polyamine gel
core and PEG chains1. TEM images revealed that the synthesized GNPs located only in the
nanogel core, indicating that nanogel acted as both nanoreactor and nanoreservoir for GNPs.
Additionally, number of GNPs in sigle nanogel could be easily arranged by changing N / Au
(number of amino groups / number of Au atoms) ratio. The obtained gold naoparticle containing
nanogels (GNG) were applied for an enhancement of cancer phtothermal therapy as well as
radiotherapy in response to electromagnetic wave in cultured cancer cells.
Cancer photothermal effect was tested using HeLa cells (10 5 cells / well) after treatment with
GNG(1) ([Au] = 168 µg / mL). Figure 1 shows fluorescence microscopy image of double-stained
HeLa cells after irradiation of Ar + laser (514.5 nm, 51mW / cm 2 , d
= 1 mm) for 5 min. As can be seen in Figure 1, dead cells (red
fluorescence) were clearly observed only in the laser irradiationregion
(inner of yellow circle), whereas the living cells (green
fluorescence) were only observed out of the laser irradiationregion.
This result strongly indicates that pinpoint cancer
photothermal therapy was successfully achieved using GNG.
Radiotherapy was carried out using A549 cells (200 cells / dish in
case of 4 Gy irradiation sample) after treatment with GNG(2)
([Au] = 15 µg / mL) or the PEGylated nanogels without GNPs.
The results of giemusa-stained colony assay of A549 cells
showed that the number of the colony decreased after irradiation
of 4, 8, 12, 16 Gy of X-ray (200 kV, 20 mA, 4 Gy / min). These
results clearly show that GNG acted as an efficient radioenhancer,
which may reduce the side effect of cancer radiotherapy. In
conclusion, noninvasive photothermal and radio therapy were
successfully achieved using GNG as electromagnetic enhancer.
This study was carried out by group of Nagasaki Laboratory
in University of Tsukuba collaborated with Prof. Matsuishi Lab
in U.Tsukuba and Prof.Inanami in Hokkaid U. The author
appreciates, Professors K.Matsuishi, O.Inanami, M.Oishi, Drs.
H.Yasui and H.Hayashi, Messrs. A.Tamura, T.Nakamura, Y.Jinji
and R.Takeuchi for their collaboration of this study.
References:
Oral Presentation 11
TEM of
Gold-containing
Nanogel
Fig.1 Fluorescence microscope image
of double-stained Hela cells after laser
irradiation.
M. Oishi, H. Hayashi, T. Uno, T. Ishii, M. Iijima, and Y. Nagasaki, Macromol. Chem. Phys., 208,
1176-1182 (207).
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