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Enhanced endosomal escape by photothermal activation for improved small interfering RNA delivery and antitumor effect
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 a...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061202/ https://www.ncbi.nlm.nih.gov/pubmed/30087564 http://dx.doi.org/10.2147/IJN.S161908 |
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author | Yang, Xi Fan, Bo Gao, Wei Li, Liping Li, Tingting Sun, Jinghua Peng, Xiaoyang Li, Xiaoyan Wang, Zhenjun Wang, Binquan Zhang, Ruiping Xie, Jun |
author_facet | Yang, Xi Fan, Bo Gao, Wei Li, Liping Li, Tingting Sun, Jinghua Peng, Xiaoyang Li, Xiaoyan Wang, Zhenjun Wang, Binquan Zhang, Ruiping Xie, Jun |
author_sort | Yang, Xi |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6061202 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-60612022018-08-07 Enhanced endosomal escape by photothermal activation for improved small interfering RNA delivery and antitumor effect Yang, Xi Fan, Bo Gao, Wei Li, Liping Li, Tingting Sun, Jinghua Peng, Xiaoyang Li, Xiaoyan Wang, Zhenjun Wang, Binquan Zhang, Ruiping Xie, Jun Int J Nanomedicine Original Research 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. Dove Medical Press 2018-07-23 /pmc/articles/PMC6061202/ /pubmed/30087564 http://dx.doi.org/10.2147/IJN.S161908 Text en © 2018 Yang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Yang, Xi Fan, Bo Gao, Wei Li, Liping Li, Tingting Sun, Jinghua Peng, Xiaoyang Li, Xiaoyan Wang, Zhenjun Wang, Binquan Zhang, Ruiping Xie, Jun Enhanced endosomal escape by photothermal activation for improved small interfering RNA delivery and antitumor effect |
title | 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_short | 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 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061202/ https://www.ncbi.nlm.nih.gov/pubmed/30087564 http://dx.doi.org/10.2147/IJN.S161908 |
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