期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 13, 期 -, 页码 4333-4344出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S161908
关键词
melanin; poly-L-lysine; photothermal effect; endosomal escape; siRNA delivery
资金
- National Natural Science Foundation of China [81571747, 81771907]
- Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province, Shanxi Scholarship Council of China [2015057]
- Key research and development project of Shanxi Province [2016021, 201703D321015-3]
- Science and technology innovation team project [201705D131026]
- Scientific and technological achievements transformation project of Shanxi Province [201704D131006]
- Shanxi Province Science Foundation for Youths [201701D221257]
- Foundation for PhD of Shanxi Medical University [03201620]
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.
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