Codelivery of a cytotoxin and photosensitiser via a liposomal nanocarrier: a novel strategy for light-triggered cytosolic release.
Codelivery of a cytotoxin and photosensitiser via a liposomal nanocarrier: a novel strategy for light-triggered cytosolic release.
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DOI：
10.1039/c8nr04048f
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发表时间：
2018-11-08
期刊：
影响因子：
6.7
通讯作者：
Eggleston IM
中科院分区：
文献类型：
--
作者：
Yaghini E ;Dondi R ;Edler KJ ;Loizidou M ;MacRobert AJ ;Eggleston IM
蛋白质毒素的光触发细胞内递送是通过脂质体纳米载体实现的，该载体以细胞穿透肽(CPP)-光敏剂结合物为靶标。对于许多纳米级生物治疗药物的胞浆或胞核靶标的胞内输送来说，胞体包埋是一个关键问题。光化学内化(PCI)是一种新型的基于光的解决方案，可用于触发一系列生物活性物质内体逃逸到胞浆中，从而提高临床前和临床研究的效率。经皮冠状动脉介入治疗通常依赖于生物活性物质与单独给药的适当光敏剂的内溶酶体共定位。在这项研究中，我们证明了这两种成分可以通过一种新型的多功能脂质体纳米载体结合在一起进行联合传递，并相应地提高了包封剂的生物学效力。作为概念的证据，我们在这里展示了30 kDa蛋白毒素皂苷在MC28纤维肉瘤细胞中的细胞毒性显著增强，当通过细胞穿透肽(CPP)修饰的脂质体传递时，CPP另外还具有针对内溶酶体膜的光敏剂的功能。这一创新为通过经皮冠状动脉介入治疗方法有效地提供一系列生物治疗药物开辟了道路，结合了经过临床验证的脂质体输送平台，并使用生物正交连接化学物质来添加光敏剂和所选的多肽。
Light-triggered intracellular delivery of a protein toxin was achieved by codelivery via a liposomal nanocarrier, targeted with a cell-penetrating peptide (CPP)–photosensitiser conjugate. Endosomal entrapment is a key issue for the intracellular delivery of many nano-sized biotherapeutics to their cytosolic or nuclear targets. Photochemical internalisation (PCI) is a novel light-based solution that can be used to trigger the endosomal escape of a range of bioactive agents into the cytosol leading to improved efficacy in pre-clinical and clinical studies. PCI typically depends upon the endolysosomal colocalisation of the bioactive agent with a suitable photosensitiser that is administered separately. In this study we demonstrate that both these components may be combined for codelivery via a novel multifunctional liposomal nanocarrier, with a corresponding increase in the biological efficacy of the encapsulated agent. As proof of concept, we show here that the cytotoxicity of the 30 kDa protein toxin, saporin, in MC28 fibrosarcoma cells is significantly enhanced when delivered via a cell penetrating peptide (CPP)-modified liposome, with the CPP additionally functionalised with a photosensitiser that is targeted to endolysosomal membranes. This innovation opens the way for the efficient delivery of a range of biotherapeutics by the PCI approach, incorporating a clinically proven liposome delivery platform and using bioorthogonal ligation chemistries to append photosensitisers and peptides of choice.
影响因子：
3.7
作者：
Itakura S;Hama S;Ohgita T;Kogure K
通讯作者：
Kogure K