Photochemical internalization provides time- and space-controlled endolysosomal escape of therapeutic molecules
Photochemical internalization provides time- and space-controlled endolysosomal escape of therapeutic molecules
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DOI：
10.1016/j.jconrel.2010.06.008
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发表时间：
2010-11-20
影响因子：
10.8
通讯作者：
Berg, Kristian
中科院分区：
文献类型：
--
作者：
Selbo, Pal Kristian;Weyergang, Anette;Berg, Kristian
利用细胞内靶点的生物药物成功治愈癌症取决于将药物特异性和充分地输送到恶性细胞的细胞质或细胞核中。然而，膜不渗透癌症治疗的细胞质递送和疗效经常受到内溶酶体腔室中药物的隔离和降解的阻碍。因此，我们开发了光化学内化（PCI）作为一种位点特异性药物递送技术，该技术可以击破内吞囊泡的膜，诱导被包裹的药物释放到光照射细胞的细胞质中。PCI的原理已在不同实验室的80种不同的细胞系和10种不同的各种癌症的异种移植模型中得到证实，显示了其广泛的应用潜力。本文将介绍pci诱导的蛋白或核酸为基础的内体逃逸疗法和一些化疗药物。在生命科学家的共同努力下，PCI技术目前正处于I/II期临床试验阶段，在治疗实体肿瘤方面取得了非常有希望的初步结果。(C) 2010 Elsevier B.V.版权所有
A successful cure of cancer by biopharmaceuticals with intracellular targets is dependent on both specific and sufficient delivery of the drug to the cytosol or nuclei of malignant cells. However, cytosolic delivery and efficacy of membrane-impermeable cancer therapeutics are often hampered by the sequestration and degradation of the drugs in the endolysosomal compartments. Hence, we developed photochemical internalization (PCI) as a site-specific drug delivery technology, which bursts the membrane of endocytic vesicles inducing release of entrapped drugs to the cytosol of light exposed cells. The principle of PCI has been demonstrated in >80 different cell lines and 10 different xenograft models of various cancers in different laboratories demonstrating its broad application potential. PCI-induced endosomal escape of protein- or nucleic acid-based therapeutics and some chemotherapeutics will be presented in this review. With a joint effort by life scientists the PCI technology is currently in a Phase I/II clinical trial with very promising initial results in the treatment of solid tumors. (C) 2010 Elsevier B.V. All rights reserved.