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大环光敏剂与细胞相互作用的结构和物理化学决定因素。

Structural and physico-chemical determinants of the interactions of macrocyclic photosensitizers with cells.

作者信息

Mojzisova Halina, Bonneau Stéphanie, Brault Daniel

机构信息

Laboratoire de Biophysique Moléculaire Cellulaire et Tissulaire (BIOMOCETI), CNRS UMR 7033, Université Pierre and Marie Curie, Genopole Campus 1, 5 rue Henri Desbruères, 91030, Evry Cedex, Paris, France.

出版信息

Eur Biophys J. 2007 Nov;36(8):943-53. doi: 10.1007/s00249-007-0204-9. Epub 2007 Jul 13.

DOI:10.1007/s00249-007-0204-9
PMID:17628795
Abstract

New therapies have been developed using reactive oxygen species produced by light-activation of photosensitizers (PS). Since the lifetime of these species is extremely short and their diffusion in space is limited, the photo-induced reactions primarily affect the cell organelles labeled by the PS. In addition to the development of molecules with the best optical and photosensitizing properties, considerable research has been done to understand the physico-chemical parameters governing their subcellular localization. In this review, we examine these parameters to establish the structure/efficacy relationships, which allow specific targeting of PS. We examine the effect of subcellular localization on the cellular response to photosensitization processes. We discuss the determinants of subcellular localization, including the hydrophobic/hydrophilic balance, the specific charge effects and the dynamics of PS' transfer through membranes. Specific targeting can also be achieved with molecular structures able to recognize cellular or intracellular receptors, and this is also dealt with in this paper.

摘要

利用光激活光敏剂(PS)产生的活性氧开发了新的治疗方法。由于这些物质的寿命极短且在空间中的扩散有限,光诱导反应主要影响被PS标记的细胞器。除了开发具有最佳光学和光敏特性的分子外,还进行了大量研究以了解控制其亚细胞定位的物理化学参数。在这篇综述中,我们研究这些参数以建立结构/功效关系,从而实现PS的特异性靶向。我们研究亚细胞定位对细胞对光致敏过程反应的影响。我们讨论亚细胞定位的决定因素,包括疏水/亲水平衡、特定电荷效应以及PS通过膜的转移动力学。通过能够识别细胞或细胞内受体的分子结构也可以实现特异性靶向,本文也将对此进行探讨。

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