@misc{oai:repo.qst.go.jp:00069548,
 author = {Mizuno, Kazue and Mori, Azusa and Yusa, Noritaka and Konishi, Teruaki and Hamano, Tsuyoshi and Ishikawa, Takahiro and Iso, Hiroyuki and Kato, Takamitsu and Okayasu, Ryuichi and Imaseki, Hitoshi and Uesaka, Mitsuru and 小西 輝昭 and 濱野 毅 and 石川 剛弘 and 磯 浩之 and 加藤 宝光 and 岡安 隆一 and 今関 等},
 month = {Oct},
 note = {Background/Aim:
     X-ray Drug Delivery System (DDS) is a combination of pinpoint X-ray and
DDS, which can reduce side effects of radiation and chemicals.  Polymeric
micelle is one of the most promising DDS carriers having long circulation
and high accumulation in solid tumor.  Cisplatin micelle is a newly
developed DDS drug which contains cisplatin (1 nm) in a polymeric micelle
(30 nm).  The micelle collapses in the presence of chlorine ion, and the
drug is gradually released. To optimize the therapeutic effect, the uptake
characteristics of DDS drugs should be fully understood. The aim of this
study is to directly measure cellular uptake of cisplatin micelle by using
Particle Induced X-ray Emission (PIXE).
Methods:
     Chinese Hamster Ovary cells were treated with cisplatin or cisplatin
micelle for 0.5-24 hours.  The PIXE analysis was conducted at National
Institute of Radiological Sciences, Chiba, Japan.  By counting the number of
characteristic X-rays emitted during proton beam irradiation, the elemental
distribution was obtained.  The signals of Pt-L alpha (9.441 keV) were
corresponding to the amount of platinum contained in the cells.
Results:
     After 24-hours incubation, the Pt signal from the cells treated with
cisplatin micelle was about 1/9 of that of cisplatin alone.  This result
suggests that cisplatin contained in a micelle is not well released in 24
hours.  Next, the cisplatin micelle was exposed to the media, which contains
chlorine ion, before the 24-hours incubation.  The exposure improved the
uptake.  Amount of Pt in the cells agreed with collapsed amount of the
micelle.
Conclusion:
     Uptake of cisplatin micelle was directly observed by PIXE.  The
micelles (30nm) did not pass through the cellular membrane, and their
collapsing rate (releasing rate of cisplatin) played an important role in
cytotoxicity.  The obtained information is useful for application of DDS
drugs to radiation therapy., 8th ASIA OCEANIA CONGRESS OF MEDICAL PHYSICS},
 title = {PIXE ANALYSIS OF PLATINUM-CONTAINING DDS DRUGS},
 year = {2008}
}