title: Biodegradable stearylated peptide with internal disulfide bonds for efficient delivery of siRNA in vitro and in vivo.
abstract: RNA-based delivery system for cancer therapy remains a challenge. In this study, a stearyl-peptide (SHR) was synthesized using arginine, histidine, cysteine, and stearyl moieties. Further, the stearyl-peptides were cross-linked by disulfide bonds to obtain cross-linked polypeptides (SHRss) with different molecular weight (SHRss1, SHRss2, SHRss3, SHRss4). The SHRss could effectively condense small interfering RNA (siRNA) into polyplexes with a hydrodynamic size of 100-300 nm and zeta potential of 20-40 mV. Flow cytometry and confocal laser scanning microscope studies revealed high cellular uptake and rapid dissociation behavior of SHRss2/siRNA complexes. Long-lasting high concentration of siRNA in cytoplasm was observed even at 24 h after SHRss2/Cy3-siRNA transfection. Compared with SHR, the SHRss showed much improved siRNA interference efficiency targeting luciferase on Luc-Hela cells. Moreover, SHRss2 exhibited higher interference efficiency and slower decay rate on Luc-Hela cells than Lipofectamine 2000 and SHR. In addition, much weaker expression of red fluorescence protein was also observed on SHRss2/simCh-treated mCherry-HEK293 cells than Lipofectamine 2000 and SHR. The SHRss did not induce cytotoxicity at siRNA concentrations of 25-200 nM under transfection. The in vivo studies demonstrated the gene interference efficiency of SHRss2/siRNA complexes. Our studies indicated that the SHRss are promising and efficient nonviral vectors for siRNA delivery.
authors: †Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Zongguang
authors: Z
authors: Tai
authors: †Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Xiaoyu
authors: X
authors: Wang
authors: †Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Jing
authors: J
authors: Tian
authors: †Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Yuan
authors: Y
authors: Gao
authors: †Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Lijuan
authors: L
authors: Zhang
authors: †Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Chong
authors: C
authors: Yao
authors: §Department of Pharmaceutics, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China.
authors: Xin
authors: X
authors: Wu
authors: †Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Wei
authors: W
authors: Zhang
authors: †Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.|∥Department of Pharmacy, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
authors: Quangang
authors: Q
authors: Zhu
authors: †Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors: Shen
authors: S
authors: Gao
mesh_terms: D000818:Animals; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000493:pharmacokinetics; D004220:Disulfides / Q000737:chemistry*; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D055666:Lipopeptides / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D000067492:RNAi Therapeutics / Q000379:methods; D013229:Stearic Acids / Q000737:chemistry*
chemical_list: D057846:Cell-Penetrating Peptides; D004220:Disulfides; D055666:Lipopeptides; D034741:RNA, Small Interfering; D013229:Stearic Acids; C031183:stearic acid