| セッション情報 |
International Forum 2(Liver) 4.Treatment Strategy
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| タイトル |
IF2-4-V (Plenary presentation) Targeted dual therapy for hepatocellular carcinoma using drug-loaded superparamagnetic nanoparticles
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| 演者 |
Jason Chang（Dept of Gastroenterology and HepatologySingapore General HospitalSingapore^1） |
| 共同演者 |
H Rumpel（Dept of Diagnostic RadiologySingapore General HospitalSingapore^2）, IHC Kee（Dept of Experimental SurgerySingapore General HospitalSingapore^3）, S Purushotham（School of Materials EngineeringNanyang Technological UniversitySingapore^4）, RTH Ng（Dept of Experimental SurgerySingapore General HospitalSingapore^3）, PKH Chow（Dept of Experimental SurgerySingapore General HospitalSingapore^3）, RV Ramanujan（School of Materials EngineeringNanyang Technological UniversitySingapore^4）, CK Tan（Dept of Gastroenterology and HepatologySingapore General HospitalSingapore^1） |
| 抄録 |
Background ： Superparamagnetic iron-oxide nanoparticles （NP） are non-magnetic unless external mag-netic field （MF） is applied． Poly-N-isopropylacrylamide （PNIPA） is a thermosensitive polymer that shrinksat＞34℃． Doxorubicin-loaded-PNIPA-coated-NP exposed to MF will generate heat and doxorubicin willbe released as polymer shrinks． Hence doxorubicin-loaded-PNIPA-coated-NP can be targeted dual ther-apy for hepatocellular carcinoma （HCC）．Aims：To show（1）doxorubicirloadedっ01ymer-coated-NP can be delivered intra-arterially to targethuman HCC in a rat model （2） heat is generated when MF is applied （3） doxorubicin is released in a con-trolled fashion when doxorubicin-loaded-polymer-coated-NP is heatedMethods ： Morris hepatoma cells are implanted into liver of buffalo rats． MRI is done after 2 weeks toconfirm HCC development． O．5ml of doxorubicin-loaded-polymer-coated-NP solution is injected into thehepatic artery and MRI performed to confirm localization of NP in HCC． Rats are sacrificed and histologyof liverstomachkidneyspleen and lung obtained． A MF is applied to the doxorubicin-loaded-polymer-coated-NP solution and the temperature measured to demonstrate heat effect． The amount of doxorubi-cin released is measured by spectrophotometry．Results：Successful intra-arterial delivery of NP was confirmed ori post-injection MRI scan． Iron parti-cles were seen on H＆E stain in tumor tissue but not in normal liver or other organs． When MF was ap-plied for 800sectemperature of NP solution rose from 200C and plateaued at 430C． When doxorubicin-loaded-PNIPA-coated-NP solution was subjected to MFtemperature increased to 48℃during which4．6% of doxorubicin by weight was released．Conclusions ： We have demonstrated in a rat model for the first time the feasibility of using doxorubicin-loaded-PNIPA-coated-NP for synergistic dual therapy of targeted hyperthermia and cytotoxic killing ofHCC． |
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