PMID- 30087564 OWN - NLM STAT- MEDLINE DCOM- 20180910 LR - 20230926 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 13 DP - 2018 TI - Enhanced endosomal escape by photothermal activation for improved small interfering RNA delivery and antitumor effect. PG - 4333-4344 LID - 10.2147/IJN.S161908 [doi] AB - 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. FAU - Yang, Xi AU - Yang X AD - Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China, xiejun1968@126.com. AD - Imaging Department of Shanxi Provincial Cancer Hospital, Shanxi Medical University, Imaging Department of Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China, zrp_7142@163.com. FAU - Fan, Bo AU - Fan B AD - Department of Pharmacy, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China. FAU - Gao, Wei AU - Gao W AD - Department of Otolaryngology, Head and Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China. AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, Shanxi, People's Republic of China. FAU - Li, Liping AU - Li L AD - Imaging Department of Shanxi Provincial Cancer Hospital, Shanxi Medical University, Imaging Department of Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China, zrp_7142@163.com. FAU - Li, Tingting AU - Li T AD - Department of Pharmacy, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China. FAU - Sun, Jinghua AU - Sun J AD - Imaging Department of Shanxi Provincial Cancer Hospital, Shanxi Medical University, Imaging Department of Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China, zrp_7142@163.com. FAU - Peng, Xiaoyang AU - Peng X AD - Imaging Department of Shanxi Provincial Cancer Hospital, Shanxi Medical University, Imaging Department of Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China, zrp_7142@163.com. FAU - Li, Xiaoyan AU - Li X AD - Imaging Department of Shanxi Provincial Cancer Hospital, Shanxi Medical University, Imaging Department of Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China, zrp_7142@163.com. FAU - Wang, Zhenjun AU - Wang Z AD - Imaging Department of Shanxi Provincial Cancer Hospital, Shanxi Medical University, Imaging Department of Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China, zrp_7142@163.com. FAU - Wang, Binquan AU - Wang B AD - Department of Otolaryngology, Head and Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China. AD - Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, Shanxi, People's Republic of China. FAU - Zhang, Ruiping AU - Zhang R AD - Imaging Department of Shanxi Provincial Cancer Hospital, Shanxi Medical University, Imaging Department of Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China, zrp_7142@163.com. FAU - Xie, Jun AU - Xie J AD - Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China, xiejun1968@126.com. LA - eng PT - Journal Article DEP - 20180723 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 RN - 0 (Antineoplastic Agents) RN - 0 (Birc5 protein, mouse) RN - 0 (Inhibitor of Apoptosis Proteins) RN - 0 (Melanins) RN - 0 (RNA, Small Interfering) RN - 0 (Repressor Proteins) RN - 0 (Survivin) RN - 25104-18-1 (Polylysine) RN - EC 1.13.12.- (Luciferases) SB - IM MH - Animals MH - Antineoplastic Agents/*pharmacology MH - Apoptosis/drug effects MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Down-Regulation/drug effects MH - Endosomes/drug effects/*metabolism MH - Female MH - Gene Expression MH - Gene Silencing/drug effects MH - *Gene Transfer Techniques MH - Humans MH - Inhibitor of Apoptosis Proteins/metabolism MH - *Light MH - Luciferases/metabolism MH - Melanins/chemistry MH - Mice, Inbred BALB C MH - Nanoparticles/administration & dosage/ultrastructure MH - Neoplasm Metastasis MH - Polylysine/chemistry MH - RNA, Small Interfering/*administration & dosage/genetics MH - Repressor Proteins/metabolism MH - Survivin MH - *Temperature PMC - PMC6061202 OTO - NOTNLM OT - endosomal escape OT - melanin OT - photothermal effect OT - poly-L-lysine OT - siRNA delivery COIS- Disclosure The authors report no conflicts of interest in this work. EDAT- 2018/08/09 06:00 MHDA- 2018/09/11 06:00 PMCR- 2018/07/23 CRDT- 2018/08/09 06:00 PHST- 2018/08/09 06:00 [entrez] PHST- 2018/08/09 06:00 [pubmed] PHST- 2018/09/11 06:00 [medline] PHST- 2018/07/23 00:00 [pmc-release] AID - ijn-13-4333 [pii] AID - 10.2147/IJN.S161908 [doi] PST - epublish SO - Int J Nanomedicine. 2018 Jul 23;13:4333-4344. doi: 10.2147/IJN.S161908. eCollection 2018.