Photochemical Internalization (PCI): A Technology for Drug Delivery
Photochemical Internalization (PCI): A Technology for Drug Delivery
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DOI：
10.1007/978-1-60761-697-9_10
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Selbo, Pal K.
中科院分区：
文献类型：
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作者：
Berg, Kristian;Weyergang, Anette;Selbo, Pal K.
在癌症和其它疾病的治疗中使用大分子变得越来越重要。分子生物学和生物技术的最新进展使得有可能改进细胞毒性剂、DNA复合物和其他用于临床应用的大分子的靶向和设计。为了实现这些大分子的预期生物学效应，在许多情况下，内化至细胞胞质溶胶是至关重要的。在细胞内水平，治疗分子胞质释放的最基本障碍是内吞囊泡的膜屏障。光化学内化（PCI）是一种将细胞内吞的大分子物质释放到胞质溶胶中的新技术。该技术基于使用位于内吞囊泡中的光敏剂，其在被光激活后诱导大分子从其在内吞囊泡中的区室化中释放。PCI已显示出增强大量不容易穿透质膜的大分子和其他分子的生物活性，包括I型核糖体失活蛋白（RIP）、基因编码质粒、腺病毒、寡核苷酸和化疗博来霉素。PCI还显示出增强靶向治疗性大分子的治疗效果。本方案描述了通过链霉亲和素生物素连接的表皮生长因子受体（EGFR）靶向蛋白毒素（西妥昔单抗皂草素）的PCI，用于筛选靶向毒素，以及基于非病毒聚合物的基因治疗的PCI。尽管详细描述了靶蛋白毒素和DNA聚合复合物的PCI，但这些方案中提出的方法也适用于其他基因治疗载体（例如，病毒载体）、肽核酸（PNA）、小干扰RNA（siRNA）、聚合物、纳米颗粒和一些化疗剂。
The utilization of macromolecules in therapy of cancer and other diseases is becoming increasingly relevant. Recent advances in molecular biology and biotechnology have made it possible to improve targeting and design of cytotoxic agents, DNA complexes, and other macromolecules for clinical applications. To achieve the expected biological effect of these macromolecules, in many cases, internalization to the cell cytosol is crucial. At an intracellular level, the most fundamental obstruction for cytosolic release of the therapeutic molecule is the membrane-barrier of the endocytic vesicles. Photochemical internalization (PCI) is a novel technology for release of endocytosed macromolecules into the cytosol. The technology is based on the use of photosensitizers located in endocytic vesicles that upon activation by light induces a release of macromolecules from their compartmentalization in endocytic vesicles. PCI has been shown to potentiate the biological activity of a large variety of macromolecules and other molecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), gene-encoding plasmids, adenovirus, oligonucleotides, and the chemotherapeutic bleomycin. PCI has also been shown to enhance the treatment effect of targeted therapeutic macromolecules. The present protocol describes PCI of an epidermal growth factor receptor (EGFR)-targeted protein toxin (Cetuximab saporin) linked via streptavidin biotin for screening of targeted toxins as well as PCI of non-viral polyplex-based gene therapy. Although describing in detail PCI of targeted protein toxins and DNA polyplexes, the methodology presented in these protocols are also applicable for PCI of other gene therapy vectors (e.g., viral vectors), peptide nucleic acids (PNA), small interfering RNA (siRNA), polymers, nanoparticles, and some chemotherapeutic agents.