Structural factors and mechanisms underlying the improved photodynamic cell killing with silicon phthalocyanine photosensitizers directed to lysosomes versus mitochondria.
Structural factors and mechanisms underlying the improved photodynamic cell killing with silicon phthalocyanine photosensitizers directed to lysosomes versus mitochondria.
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DOI：
10.1111/j.1751-1097.2009.00558.x
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发表时间：
2009-09
影响因子：
3.3
通讯作者：
Oleinick NL
中科院分区：
文献类型：
--
作者：
Rodriguez ME;Zhang P;Azizuddin K;Delos Santos GB;Chiu SM;Xue LY;Berlin JC;Peng X;Wu H;Lam M;Nieminen AL;Kenney ME;Oleinick NL
酞菁光敏剂Pc 4已被证明优先与线粒体和内质网膜结合。在光照射的Pc 4-负载的细胞，膜组件，特别是Bcl-2，是光损伤和细胞凋亡，所示的激活的半胱天冬酶-3和裂解的聚（ADP-核糖）聚合酶，被触发。合成了一系列的Pc 4类似物，结果表明，与Pc 4的氨丙基甲硅烷氧基配体或类似的一个在Pc环的一侧和第二个大的轴向配体在环的另一侧的Pc具有意想不到的性质，包括增强的细胞摄取，更大的单体化导致更大的细胞内荧光和三倍高的亲和常数的脂质体。羟基轴承轴向配体倾向于减少PC的聚集，并将其引导至溶酶体，从而导致比PC 4多4至6倍的细胞杀伤，如通过克隆形成的损失所定义的。尽管Pc 4-PDT光损伤Bcl-2和Bcl-xL，但Pc 181-PDT在相同的剂量-反应范围内对Bcl-2的光损伤相对于细胞杀伤要少得多，Bid的裂解更早，caspase-3依赖性凋亡更慢。因此，在这一系列的光敏剂，这些羟基轴承轴向配体是较少的聚集比Pc 4，往往定位到溶酶体和更有效的整体细胞杀伤比Pc 4，但诱导细胞凋亡更缓慢，并通过修改的途径。
The phthalocyanine photosensitizer Pc 4 has been shown to bind preferentially to mitochondrial and endoplasmic reticulum membranes. Upon photoirradiation of Pc 4-loaded cells, membrane components, especially Bcl-2, are photodamaged and apoptosis, as indicated by activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase, is triggered. A series of analogs of Pc 4 were synthesized, and the results demonstrate that Pcs with the aminopropylsiloxy ligand of Pc 4 or a similar one on one side of the Pc ring and a second large axial ligand on the other side of the ring have unexpected properties, including enhanced cell uptake, greater monomerization resulting in greater intracellular fluorescence and three-fold higher affinity constants for liposomes. The hydroxyl-bearing axial ligands tend to reduce aggregation of the Pc and direct it to lysosomes, resulting in four to six times more killing of cells, as defined by loss of clonogenicity, than with Pc 4. Whereas Pc 4-PDT photodamages Bcl-2 and Bcl-xL, Pc 181-PDT causes much less photodamage to Bcl-2 over the same dose–response range relative to cell killing, with earlier cleavage of Bid and slower caspase-3-dependent apoptosis. Therefore, within this series of photosensitizers, these hydroxyl-bearing axial ligands are less aggregated than is Pc 4, tend to localize to lysosomes and are more effective in overall cell killing than is Pc 4, but induce apoptosis more slowly and by a modified pathway.
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影响因子：
13.3
作者：
Buytaert, E.;Callewaert, G.;Agostinis, P.
通讯作者：
Agostinis, P.
影响因子：
8.8
作者：
Chiu SM;Oleinick NL
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Oleinick NL
影响因子：
3.3
作者：
Xue, Liang-Yan;Chiu, Song-Mao;Oleinick, Nancy L.
通讯作者：
Oleinick, Nancy L.
影响因子：
3.7
作者：
Xue, LY;Chiu, SM;Oleinick, NL
通讯作者：
Oleinick, NL
影响因子：
1.5
作者：
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通讯作者：
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