Peptide-mediated cell penetration and targeted delivery of gold nanoparticles into lysosomes
Peptide-mediated cell penetration and targeted delivery of gold nanoparticles into lysosomes
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DOI：
10.1002/psc.2430
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发表时间：
2012-08-01
影响因子：
2.1
通讯作者：
Fecondo, John V.
中科院分区：
文献类型：
--
作者：
Dekiwadia, Chaitali D.;Lawrie, Ann C.;Fecondo, John V.
人们对生物分子、治疗剂和成像剂以及纳米颗粒和纳米颗粒缀合物的亚细胞靶向和递送进入细胞器以用于治疗和成像目的具有相当大的兴趣。迄今为止，许多研究已经使用分选肽将货物靶向递送到不同的细胞器中，但不递送到溶酶体中。在这项研究中，使用细胞穿透肽和与纳米颗粒缀合的溶酶体分选肽的新型组合来检查 13 nm 金纳米颗粒穿过细胞膜的递送，然后靶向定位到哺乳动物细胞系的溶酶体中。通过结合荧光光谱、荧光显微镜和透射电子显微镜技术，我们证明这些纳米缀合物可以有效、选择性地递送到溶酶体中，且细胞毒性作用最小。这种新颖的靶向递送系统可以通过利用纳米颗粒的大表面积将药物或替代酶直接递送至溶酶体，从而支持开发治疗溶酶体贮积病的新策略。版权所有 (c) 2012 欧洲肽协会和 John Wiley & Sons, Ltd.
There is considerable interest in the sub-cellular targeting and delivery of biomolecules, therapeutic and imaging agents, and nanoparticles and nanoparticle conjugates into organelles for therapeutic and imaging purposes. To date, a number of studies have used sorting peptides for targeted delivery of cargo into different cell organelles but not into lysosomes. In this study, the delivery of 13-nm gold nanoparticles across the cell membrane followed by targeted localisation into the lysosomes of a mammalian cell line was examined using novel combinations of cell-penetrating peptides and lysosomal sorting peptides conjugated to the nanoparticles. Using a combination of fluorescence spectroscopy, fluorescence microscopy and transmission electron microscopy techniques, we show that these nanoconjugates were efficiently and selectively delivered into the lysosomes with minimal cytotoxic effects. This novel targeted delivery system may underpin the development of a new strategy for the treatment of lysosomal storage diseases by exploiting the large surface area of nanoparticles to deliver drugs or replacement enzymes directly to the lysosomes. Copyright (c) 2012 European Peptide Society and John Wiley & Sons, Ltd.