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已发表论文
通过光热活化增强内体逃逸，改善小干扰 RNA 递送和抗肿瘤作用
Authors Yang X, Fan B, Gao W, Li L, Li T, Sun J, Peng X, Li X, Wang Z, Wang B, Zhang R, Xie J
Received 9 January 2018
Accepted for publication 10 April 2018
Published 23 July 2018 Volume 2018:13 Pages 4333—4344
DOI https://doi.org/10.2147/IJN.S161908
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Alexander Kharlamov
Peer reviewer comments 5
Editor who approved publication: Dr Linlin Sun
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
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
