Title |
Enhanced endosomal escape by photothermal activation for improved small interfering RNA delivery and antitumor effect
|
---|---|
Published in |
International Journal of Nanomedicine, July 2018
|
DOI | 10.2147/ijn.s161908 |
Pubmed ID | |
Authors |
Xi Yang, Bo Fan, Wei Gao, Liping Li, Tingting Li, Jinghua Sun, Xiaoyang Peng, Xiaoyan Li, Zhenjun Wang, Binquan Wang, Ruiping Zhang, Jun Xie |
Abstract |
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. 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. 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 37 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 10 | 27% |
Student > Master | 5 | 14% |
Professor | 3 | 8% |
Researcher | 3 | 8% |
Student > Postgraduate | 2 | 5% |
Other | 6 | 16% |
Unknown | 8 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 6 | 16% |
Medicine and Dentistry | 5 | 14% |
Chemistry | 5 | 14% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
Agricultural and Biological Sciences | 2 | 5% |
Other | 6 | 16% |
Unknown | 11 | 30% |