Binding of liposomes to human bladder tumor epithelial cell lines: implications for an intravesical drug delivery system for the treatment of bladder cancer.

J W Johnson, R Nayar, J J Killion, A C von Eschenbach, I J Fidler
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引用次数: 22

Abstract

Present therapy of human superficial bladder cancer includes the intravesical administration of antitumor drugs and immunomodulators. The purpose of these studies was to determine whether liposomes can bind to human bladder cancer cells and thereby provide a mechanism to improve the delivery of anticancer agents to diseased urothelium. Negatively charged large multilamellar vesicles (MLVs) bound to four different human bladder tumor cell lines (253J, J82, T24, TCCSUP) more avidly than did small sonicated vesicles or vesicles consisting of uncharged phosphatidylcholine (PC). Of the three types of negatively charged MLVs tested, phosphatidylcholine/phosphatidylserine (7:3, mol ratio) (PC/PS) MLVs bound the most. MLV binding to tumor cells was saturable and appeared to be specific. In contrast, the binding of liposomes to normal fetal bladder cells was minimal. These data suggest that targeting of drugs to superficial bladder cancer can be achieved by the intravesical administration of PC/PS MLV.

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脂质体与人膀胱肿瘤上皮细胞系的结合:膀胱内给药系统治疗膀胱癌的意义。
目前人类浅表性膀胱癌的治疗包括膀胱内给药抗肿瘤药物和免疫调节剂。这些研究的目的是确定脂质体是否可以与人类膀胱癌细胞结合,从而提供一种机制来改善抗癌药物对病变尿路上皮的递送。带负电荷的大多层囊泡(MLVs)与四种不同的人膀胱肿瘤细胞系(253J, J82, T24, TCCSUP)的结合比小超声囊泡或由不带电荷的磷脂酰胆碱(PC)组成的囊泡更强烈。在三种带负电荷的mlv中,磷脂酰胆碱/磷脂酰丝氨酸(7∶3,摩尔比)(PC/PS)的mlv结合最多。MLV与肿瘤细胞的结合是饱和的,似乎是特异性的。相比之下,脂质体与正常胎儿膀胱细胞的结合很少。这些数据表明,通过膀胱内给药PC/PS MLV可以实现药物靶向浅表性膀胱癌。
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