リポソームを用いる脳腫瘍の化学療法に関する基礎研究—ヒトglioma細胞に対するサルファタイド挿入リポソームの親和性

BASIC STUDIES ON CHEMOTHERAPY OF BRAIN TUMORS BY MEANS OF LIPOSOMES : AFFINITY OF SULFATIDE-INSERTED LIPOSOMES TO HUMAN GLIOMA CELLS

　抄録　悪性脳腫瘍の選択的化学療法にリポソームを応用する目的でリポソームと細胞との相互作用を検討した。卵黄phosphatidylcholine,cholesterolおよびsulfatide （モル比，7：2：1）から成るリポソームにcarboxyfluoresceinまたはferritinを封入し，gliomaをはじめneuroblastoma,carcinoma,sarcoma，lymphoma等の各種ヒト培養細胞内へのリポソームの取り込みを螢光光度計，flow cytometer，電顕により観察した。細胞内へのリポソームの取り込みはリポソームの濃度に比例して増加した。しかし一定のリポソーム濃度，一定接触時間での細胞内への取り込みは，細胞種により大きな差が認められた。とくにリポソーム取り込み率はneuroblastoma細胞や他の細胞に比ベヒトglioma細胞で最も高く，より高濃度のcar-boxyfluoresceinあるいはferritinが細胞内に観察された。以上の結果よりsulfatide挿入リポソームはヒトglioma細胞に高い親和性をもち，悪性脳腫瘍に対する選択的化学療法に応用しうる可能性があると考えられる。

In order to utilize liposomes for the treatment of brain tumors, we examined the interaction between the cells and the liposomes prepared from phosphatidylcholine, cholesterol, and sulfa-tide (molar ratio, 7 : 2 : 1), which were able to deliver the encapsulated materials into the brain through the blood-brain barrier. With a variety of human cell lines, the incorporation of the lipo- somes and the release of the liposomal contents into cells were studied by spectrofluorometry and flow cytometry by use of encapsulated 6-carboxy-fluorescein. It was found that the amounts of lipo-somes incorporated into cells were dependent on the dose of liposomes and type of cells. At the same concentration of liposomes, the highest incorporation was found for glioma cells, which was further confirmed by electron microscopy with ferritin-containing liposomes. These results indicate that the liposomes composed of sulfatide, phosphatidylcholine and cholesterol have a high affinity for human glioma cells and should be useful for the chemotherapy of glioma when anti- tumor drugs are encapsulated into them.