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

Content Provider	Semantic Scholar
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
Copyright Year	2018
Abstract	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.
Starting Page	4333
Ending Page	4344
Page Count	12
File Format	PDF HTM / HTML
Alternate Webpage(s)	https://www.dovepress.com/getfile.php?fileID=43260
PubMed reference number	30087564v1
Alternate Webpage(s)	https://doi.org/10.2147/IJN.S161908
DOI	10.2147/ijn.s161908
Journal	International journal of nanomedicine
Volume Number	13
Language	English
Access Restriction	Open
Subject Keyword	Artificial nanoparticles Gene Silencing Immunostimulating conjugate (antigen) Luciferases Lysine Mammary Neoplasms Melanins Neoplasms Non-Small Cell Lung Carcinoma Pendant Dosage Form Poly A Polymers Prolymphocytic Leukemia RNA RNA, Small Interfering Spectroscopy, Near-Infrared Virus Diseases acetylsalicylic acid lysinate cancer therapy poly ICLC
Content Type	Text
Resource Type	Article