Effect of axial ligation and delivery system on the tumour-localising and -photosensitising properties of Ge(IV)-octabutoxy-phthalocyanines.
Effect of axial ligation and delivery system on the tumour-localising and -photosensitising properties of Ge(IV)-octabutoxy-phthalocyanines.
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轴向结扎和输送系统对 Ge(IV)-八丁氧基-酞菁的肿瘤定位和光敏特性的影响。
DOI：
10.1038/bjc.1995.142
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发表时间：
1995
影响因子：
8.8
通讯作者：
Rodgers,MA
中科院分区：
文献类型：
--
作者：
Soncin,M;Polo,L;Reddi,E;Jori,G;Kenney,ME;Cheng,G;Rodgers,MA
本文研究了四种带有两个烷基型轴向配体的八丁氧基锗酞菁（GePcs）的药代动力学特性和对肌内移植的MS-2纤维肉瘤Balb/c小鼠的光治疗效率。将GePCs以0.35 μ mol kg-1体重的剂量静脉注射到Cremophor乳剂或二棕榈酰磷脂酰胆碱（DPPC）的小单层脂质体中。传递系统的性质和酞菁的化学结构都被发现会影响GePCs在体内的行为。因此，与相应的脂质体递送的酞菁相比，Cremophor施用的GePCs总是产生更长的血清保留和与低密度脂蛋白（LDL）的更大关联。这导致肿瘤靶向的更高效率和选择性。这些效果是更明显的那些GePCs具有相对较长的烷基链（己基癸基）的轴向配体。注射后24小时，发现Ge-Pc（己基）2的最大肿瘤蓄积（0.67 nmol/g组织）。同样，Ge-Pc（己基）2，通过Cremophor给药，显示出最高的光疗活性对MS-2纤维肉瘤。
Four Ge (IV)-octabutoxy-phthalocyanines (GePcs) bearing two alkyl-type axial ligands were assayed for their pharmacokinetic properties and phototherapeutic efficiency in Balb/c mice bearing an intramuscularly transplanted MS-2 fibrosarcoma. The GePcs were iv injected at a dose of 0.35 mumol kg-1 body weight after incorporation into either Cremophor emulsions or small unilamellar liposomes of dipalmitoyl-phosphatidylcholine (DPPC). Both the nature of the delivery system and the chemical structure of the phthalocyanine were found to affect the behaviour of the GePcs in vivo. Thus, Cremophor-administered GePcs invariably yielded a more prolonged serum retention and a larger association with low-density lipoproteins (LDLs) as compared with the corresponding liposome-delivered phthalocyanines. This led to a greater efficiency and selectivity of tumour targeting. These effects were more pronounced for those GePcs having relatively long alkyl chains (hexyl to decyl) in the axial ligands. Maximal tumour accumulation (0.67 nmol per g of tissue) was found for Ge-Pc (hexyl) 2 at 24 h after injection. Consistently, the Ge-Pc (hexyl) 2, administered via Cremophor, showed the highest phototherapeutic activity towards MS-2 fibrosarcoma.