Martinez de Pinillos Bayona Alejandra, Moore Caroline M, Loizidou Marilena, MacRobert Alexander J, Woodhams Josephine H
UCL Division of Surgery and Interventional Sciences, University College London, London, United Kingdom.
Int J Cancer. 2016 Mar 1;138(5):1049-57. doi: 10.1002/ijc.29510. Epub 2015 Mar 23.
Photochemical internalisation (PCI) is a technique for improving cellular delivery of certain bioactive agents which are prone to sequestration within endolysosomes. There is a wide range of agents suitable for PCI-based delivery including toxins, oligonucleotides, genes and immunoconjugates which demonstrates the versatility of this technique. The basic mechanism of PCI involves triggering release of the agent from endolysosomes within the target cells using a photosensitiser which is selectively retained with the endolysosomal membranes. Excitation of the photosensitiser by visible light leads to disruption of the membranes via photooxidative damage thereby releasing the agent into the cytosol. This treatment enables the drugs to reach their intended subcellular target more efficiently and improves their efficacy. In this review we summarise the applications of this technique with the main emphasis placed on cancer chemotherapy.
光化学内化(PCI)是一种用于改善某些生物活性剂细胞递送的技术,这些生物活性剂容易被隔离在内溶酶体中。有多种适用于基于PCI递送的试剂,包括毒素、寡核苷酸、基因和免疫缀合物,这证明了该技术的多功能性。PCI的基本机制包括使用一种选择性保留在内溶酶体膜上的光敏剂触发目标细胞内溶酶体中试剂的释放。可见光对光敏剂的激发会通过光氧化损伤导致膜破裂,从而将试剂释放到细胞质中。这种处理使药物能够更有效地到达其预期的亚细胞靶点并提高其疗效。在本综述中,我们总结了该技术的应用,主要重点放在癌症化疗上。