PIXE ANALYSIS OF PLATINUM-CONTAINING DDS DRUGS

Abstract

Background/Aim: X-ray Drug Delivery System (DDS) is a combination of pinpoint X-ray andDDS, which can reduce side effects of radiation and chemicals. Polymericmicelle is one of the most promising DDS carriers having long circulationand high accumulation in solid tumor. Cisplatin micelle is a newlydeveloped DDS drug which contains cisplatin (1 nm) in a polymeric micelle(30 nm). The micelle collapses in the presence of chlorine ion, and thedrug is gradually released. To optimize the therapeutic effect, the uptakecharacteristics of DDS drugs should be fully understood. The aim of thisstudy is to directly measure cellular uptake of cisplatin micelle by usingParticle Induced X-ray Emission (PIXE).Methods: Chinese Hamster Ovary cells were treated with cisplatin or cisplatinmicelle for 0.5-24 hours. The PIXE analysis was conducted at NationalInstitute of Radiological Sciences, Chiba, Japan. By counting the number ofcharacteristic X-rays emitted during proton beam irradiation, the elementaldistribution was obtained. The signals of Pt-L alpha (9.441 keV) werecorresponding to the amount of platinum contained in the cells.Results: After 24-hours incubation, the Pt signal from the cells treated withcisplatin micelle was about 1/9 of that of cisplatin alone. This resultsuggests that cisplatin contained in a micelle is not well released in 24hours. Next, the cisplatin micelle was exposed to the media, which containschlorine ion, before the 24-hours incubation. The exposure improved theuptake. Amount of Pt in the cells agreed with collapsed amount of themicelle.Conclusion: Uptake of cisplatin micelle was directly observed by PIXE. Themicelles (30nm) did not pass through the cellular membrane, and theircollapsing rate (releasing rate of cisplatin) played an important role incytotoxicity. The obtained information is useful for application of DDSdrugs to radiation therapy.8th ASIA OCEANIA CONGRESS OF MEDICAL PHYSIC

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