Evidence for low-density lipoprotein receptor-mediated uptake of benzoporphyrin derivative.
Evidence for low-density lipoprotein receptor-mediated uptake of benzoporphyrin derivative.
复制标题
低密度脂蛋白受体介导的苯二氧蛋白衍生物摄取的证据。
DOI：
10.1038/bjc.1994.162
复制
发表时间：
1994-05
影响因子：
8.8
通讯作者：
Levy, J G
中科院分区：
文献类型：
--
作者：
Allison, B A;Pritchard, P H;Levy, J G
血浆脂蛋白，如低密度脂蛋白（LDL），已被提出，以提高交付的疏水性光敏剂恶性组织，因为肿瘤细胞已被证明有增加的LDL受体的数量。我们已经研究了这种受体在光敏剂苯并卟啉衍生物（BPD）的细胞积累中的作用。我们注意到：（1）与正常细胞系相比，LDL受体阴性成纤维细胞系的[14 C]BPD-LDL蓄积不显著;（2）在与细胞孵育期间，没有证据表明BPD与LDL解离;（3）LDL的化学乙酰化显著降低[14 C]BPD-LDL的摄取。因此，我们得出结论，几乎所有的光敏剂积累的细胞是由于特异性结合和通过LDL受体的内化。随后在M-1（甲基胆蒽诱导的横纹肌肉瘤）荷瘤DBA/2 J小鼠中的体内研究表明，与天然LDL相关的BPD的肿瘤蓄积显著（P < 0.01）高于乙酰-LDL相关的BPD。这些结果表明，LDL受体是负责LDL相关的BPD在体外和体内的积累。因此，利用该递送系统可以在临床实践中提供光动力疗法的改进。
Plasma lipoproteins, such as low-density lipoprotein (LDL), have been proposed to enhance the delivery of hydrophobic photosensitisers to malignant tissue since tumour cells have been shown to have increased numbers of LDL receptors. We have investigated the role of this receptor in the cellular accumulation of the photosensitiser benzoporphyrin derivative (BPD). We observed that: (1) [14C]BPD-LDL accumulation by LDL receptor-negative fibroblast cell lines was insignificant compared with normal cell lines; (2) there was no evidence that BPD dissociated from LDL during incubation with the cells; and (3) chemical acetylation of LDL markedly decreased the uptake of [14C]BPD-LDL. We conclude, therefore, that virtually all of the photosensitiser accumulated by the cells was due to specific binding and internalisation via the LDL receptor. Subsequent in vivo studies in M-1 (methylcholanthrene-induced rhabdomyosarcoma) tumour-bearing DBA/2J mice showed that tumour accumulation of BPD associated with native LDL was significantly (P < 0.01) enhanced over that of acetyl-LDL-associated BPD. These results indicate that the LDL receptor is responsible for the accumulation of LDL-associated BPD both in vitro and in vivo. Thus, utilisation of this delivery system may provide for improvements in photodynamic therapy in clinical practice.