Enhanced endosomal escape by photothermal activation for improved small interfering RNA delivery and antitumor effect

Enhanced endosomal escape by photothermal activation for improved small interfering RNA delivery and antitumor effect

Xi Yang,1,2,* Bo Fan,3,* Wei Gao,4,5,* Liping Li,2 Tingting Li,3 Jinghua Sun,2 Xiaoyang Peng,2 Xiaoyan Li,2 Zhenjun Wang,2 Binquan Wang,4,5 Ruiping Zhang,2 Jun Xie1 1Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2...

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Autores principales: Yang X, Fan B, Gao W, Li L, Li T, Sun J, Peng X, Li X, Wang Z, Wang B, Zhang R, Xie J
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2018
Materias:
melanin
poly-L-lysine
photothermal effect
endosomal escape
siRNA delivery
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/8642daedf7b744699cf121e71c67bd08
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spelling oai:doaj.org-article:8642daedf7b744699cf121e71c67bd082021-12-02T00:52:39ZEnhanced endosomal escape by photothermal activation for improved small interfering RNA delivery and antitumor effect1178-2013https://doaj.org/article/8642daedf7b744699cf121e71c67bd082018-07-01T00:00:00Zhttps://www.dovepress.com/enhanced-endosomal-escape-by-photothermal-activation-for-improved-smal-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xi Yang,1,2,* Bo Fan,3,* Wei Gao,4,5,* Liping Li,2 Tingting Li,3 Jinghua Sun,2 Xiaoyang Peng,2 Xiaoyan Li,2 Zhenjun Wang,2 Binquan Wang,4,5 Ruiping Zhang,2 Jun Xie1 1Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Imaging Department of Shanxi Provincial Cancer Hospital, Shanxi Medical University, Imaging Department of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Pharmacy, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 4Department of Otolaryngology, Head and Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 5Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, Shanxi, People’s Republic of China *These authors contributed equally to this work Background: Effective endosomal escape is still a critical bottleneck for intracellular delivery of small interfering RNAs (siRNAs) to maximize their therapeutic efficacy. To overcome this obstacle, we have developed a photothermally triggered system by using the near-infrared (NIR) irradiation to achieve “on-demand” endosomal escape and subsequent siRNA release into cytoplasm. Materials and methods: Herein, the poly-l-lysine (PLL) was successfully conjugated with melanin to obtain melanin-poly-l-lysine (M-PLL) polymer as a siRNA vehicle. The melanin was an efficient photothermal sensitizer, and the positive pendant amino groups of PLL could condense siRNAs to form stable complexes by electrostatic interactions. Results and discussion: Inspired by its excellent photothermal conversion efficiency, the melanin was first involved in the siRNA delivery system. Confocal laser scanning microscopic observation revealed that after cellular uptake the photothermally induced endosomal escape could facilitate siRNAs to overcome endosomal barrier and be delivered into cytoplasm, which resulted in significant silence in the luciferase expression over the NIR- and melanin-free controls. Moreover, the anti-survivin siRNA-loaded M-PLL nanoparticles displayed great inhibitory effect on 4T1 tumor growth in vitro and in vivo. Conclusion: These findings suggest that the M-PLL-mediated siRNA delivery is a promising candidate for therapeutic siRNA delivery and shows improved effect for cancer therapy via enhanced endosomal escape. Keywords: melanin, poly-l-lysine, photothermal effect, endosomal escape, siRNA deliveryYang XFan BGao WLi LLi TSun JPeng XLi XWang ZWang BZhang RXie JDove Medical Pressarticlemelaninpoly-L-lysinephotothermal effectendosomal escapesiRNA deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 4333-4344 (2018)
institution DOAJ
collection DOAJ
language EN
topic melanin
poly-L-lysine
photothermal effect
endosomal escape
siRNA delivery
Medicine (General)
R5-920
spellingShingle melanin
poly-L-lysine
photothermal effect
endosomal escape
siRNA delivery
Medicine (General)
R5-920
Yang X
Fan B
Gao W
Li L
Li T
Sun J
Peng X
Li X
Wang Z
Wang B
Zhang R
Xie J
Enhanced endosomal escape by photothermal activation for improved small interfering RNA delivery and antitumor effect
description Xi Yang,1,2,* Bo Fan,3,* Wei Gao,4,5,* Liping Li,2 Tingting Li,3 Jinghua Sun,2 Xiaoyang Peng,2 Xiaoyan Li,2 Zhenjun Wang,2 Binquan Wang,4,5 Ruiping Zhang,2 Jun Xie1 1Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Imaging Department of Shanxi Provincial Cancer Hospital, Shanxi Medical University, Imaging Department of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Pharmacy, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 4Department of Otolaryngology, Head and Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 5Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, Shanxi, People’s Republic of China *These authors contributed equally to this work Background: Effective endosomal escape is still a critical bottleneck for intracellular delivery of small interfering RNAs (siRNAs) to maximize their therapeutic efficacy. To overcome this obstacle, we have developed a photothermally triggered system by using the near-infrared (NIR) irradiation to achieve “on-demand” endosomal escape and subsequent siRNA release into cytoplasm. Materials and methods: Herein, the poly-l-lysine (PLL) was successfully conjugated with melanin to obtain melanin-poly-l-lysine (M-PLL) polymer as a siRNA vehicle. The melanin was an efficient photothermal sensitizer, and the positive pendant amino groups of PLL could condense siRNAs to form stable complexes by electrostatic interactions. Results and discussion: Inspired by its excellent photothermal conversion efficiency, the melanin was first involved in the siRNA delivery system. Confocal laser scanning microscopic observation revealed that after cellular uptake the photothermally induced endosomal escape could facilitate siRNAs to overcome endosomal barrier and be delivered into cytoplasm, which resulted in significant silence in the luciferase expression over the NIR- and melanin-free controls. Moreover, the anti-survivin siRNA-loaded M-PLL nanoparticles displayed great inhibitory effect on 4T1 tumor growth in vitro and in vivo. Conclusion: These findings suggest that the M-PLL-mediated siRNA delivery is a promising candidate for therapeutic siRNA delivery and shows improved effect for cancer therapy via enhanced endosomal escape. Keywords: melanin, poly-l-lysine, photothermal effect, endosomal escape, siRNA delivery
format article
author Yang X
Fan B
Gao W
Li L
Li T
Sun J
Peng X
Li X
Wang Z
Wang B
Zhang R
Xie J
author_facet Yang X
Fan B
Gao W
Li L
Li T
Sun J
Peng X
Li X
Wang Z
Wang B
Zhang R
Xie J
author_sort Yang X
title Enhanced endosomal escape by photothermal activation for improved small interfering RNA delivery and antitumor effect
title_short Enhanced endosomal escape by photothermal activation for improved small interfering RNA delivery and antitumor effect
title_full Enhanced endosomal escape by photothermal activation for improved small interfering RNA delivery and antitumor effect
title_fullStr Enhanced endosomal escape by photothermal activation for improved small interfering RNA delivery and antitumor effect
title_full_unstemmed Enhanced endosomal escape by photothermal activation for improved small interfering RNA delivery and antitumor effect
title_sort enhanced endosomal escape by photothermal activation for improved small interfering rna delivery and antitumor effect
publisher Dove Medical Press
publishDate 2018
url https://doaj.org/article/8642daedf7b744699cf121e71c67bd08
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