Photodynamic damage by liposome-bound porphycenes: comparison between in vitro and in vivo models.
Photodynamic damage by liposome-bound porphycenes: comparison between in vitro and in vivo models.
复制标题
脂质体结合卟啉的光动力损伤：体外和体内模型之间的比较。
DOI：
10.1016/s1011-1344(97)00110-3
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
S. Kimel
中科院分区：
文献类型：
--
作者：
Hila Toledano;R. Edrei;S. Kimel
研究了四种四甲氧基乙基卟啉（TMPn）衍生物脂质体的光动力学效应。荧光和吸收测量被用来确定在二棕榈酰磷脂酰胆碱（DPPC）脂质体的聚集，没有发现光谱变化时，溶解在有机溶液中或在水性分散体的DPPC脂质体。这表明卟啉位于脂质体的亲脂性双层中。荧光猝灭实验与I-表明，具体地说，卟啉位于脂质体双层在不同的深度，根据亲水性的卟啉侧链。建立了剂量反应关系：增加卟啉浓度或光剂量均成比例地增强损伤。在培养的MDCK细胞中，光动力损伤是根据位置：卟啉'埋'在双层内没有造成损害的细胞培养。还通过对受精鸡胚的绒毛尿囊膜（CAM）的血管的损伤在体内测试PDT功效。与体外情况不同，“埋”在双层内的卟啉在体内确实引起了显着的光动力学损伤。这种差异表明，在体外光动力作用后，接触介导的敏化剂从脂质体转移到细胞膜，这仍然不同于细胞，而在体内的光敏剂通过脂质体与内皮细胞膜的融合传递到组织。
Photodynamic efficacy of four tetrakis(methoxyethyl)porphycene (TMPn) derivatives encapsulated in liposomes, was studied in vitro and in vivo. Fluorescence and absorption measurements were used to determine aggregation in dipalmitoyl phosphatidylcholine (DPPC) liposomes; no spectral changes were found when dissolving in an organic solution or in an aqueous dispersion of DPPC liposomes. This indicates that the porphycenes were located in the lipophilic bilayer of the liposomes. Fluorescence quenching experiments with I−showed, specifically, that porphycenes located in the liposome bilayer at various depths, according to the hydrophilicity of the porphycene side chains. Doseresponse relations were established: increasing porphycene concentration or light dose enhanced the damage proportionally. In cultured MDCK cells, photodynamic damage was in accordance with location: a porphycene ‘buried’ inside the bilayer did not cause damage to the cell culture. PDT efficacy was tested also in vivo by the damage to blood vessels of the chorioallantoic membrane (CAM) of the fertilized chick embryo. Unlike in the in vitro case, the porphycene ‘buried’ inside the bilayer did cause significant photodynamic damage in vivo. This difference suggests that in vitro photodynamic action follows contact-mediated sensitizer transfer to cell membranes from liposomes, which remain distinct from cells, whereas in vivo the photosensitizer is delivered to tissue via fusion of liposomes with endothelial cell membranes.