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首页> 外文会议>Optical Methods for Tumor Treatment and Early Diagnosis: Mechanisms and Techniques >Efficacy of photodynamic killing with membrane associated and internalized photosensitizer molecules
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Efficacy of photodynamic killing with membrane associated and internalized photosensitizer molecules

机译：与膜结合和内在化的光敏剂分子的光动力杀伤功效

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Abstract: Many photosensitizers under investigation for possible use in PDT share the property of selective accumulation in malignant or abnormal tissues. However, the mechanisms by which this occurs is not understood. Although it has been established that singlet oxygen is responsible for cell killing once a photosensitizer has reached the target tissue, the cellular targets and molecular mechanisms also remain unknown. The mechanisms of selective accumulation and cytotoxicity may depend upon the photosensitizer used. In attempts to develop technology to improve selective uptake by target tissues, the authors address the question of cellular targets at a preliminary level. These studies were performed using one benzoporphyrin derivative analogue, benzoporphyrin mono-acid ring A (BPD-MA). Plasma distribution of BPD-MA shows that this lipophilic photosensitizer has a propensity to associate with plasma lipoproteins in blood. Biodistribution studies indicate that preincubation of BPD-MA with low density lipoprotein (LDL) leads to significantly greater tumor accumulation than BPD-MA in aqueous solution. Further, the technology for conjugating BPD-MA to monoclonal antibodies has been established in the laboratory. Selective photodynamic killing of a human squamous cell carcinoma cell line (A549) has been demonstrated using such a conjugate. The monoclonal antibody (MoAb) used, 5E8, has specificity for a glycoprotein detected on human squamous cell carcinoma of the lung. In this study these two delivery systems are used to compare the cytotoxicity of membrane bound and internalized photosensitizer at the cellular level. The results indicate that LDL or MoAb mediated delivery increases the selectivity and cytotoxicity of BPD-MA. Internalization of BPD-MA via either delivery mode produces significantly enhanced cell killing.!
机译：摘要：正在研究中的许多可能在PDT中使用的光敏剂都具有在恶性或异常组织中选择性积累的特性。但是，这种情况发生的机理尚不清楚。尽管已经确定一旦光敏剂到达靶组织，单线态氧就可以杀死细胞，但是细胞靶和分子机制仍然未知。选择性积累和细胞毒性的机制可能取决于所使用的光敏剂。在尝试开发改善靶组织选择性摄取的技术的过程中，作者在初步的水平上解决了细胞靶的问题。这些研究是使用一种苯并卟啉衍生物类似物苯并卟啉单酸环A（BPD-MA）进行的。 BPD-MA的血浆分布表明，这种亲脂性光敏剂具有与血液中血浆脂蛋白缔合的倾向。生物分布研究表明，与水溶液中的BPD-MA相比，将BPD-MA与低密度脂蛋白（LDL）进行预孵育会导致明显的肿瘤蓄积。此外，在实验室中已经建立了将BPD-MA与单克隆抗体缀合的技术。使用这种缀合物已经证明了对人鳞状细胞癌细胞系（A549）的选择性光动力杀死。使用的单克隆抗体（MoAb）5E8对在人肺鳞状细胞癌中检测到的糖蛋白具有特异性。在这项研究中，这两种传递系统用于在细胞水平上比较膜结合和内在化光敏剂的细胞毒性。结果表明，LDL或MoAb介导的传递增加了BPD-MA的选择性和细胞毒性。通过任何一种输送方式对BPD-MA进行内在化都会显着增强细胞杀伤力。

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