A specific aptamer-cell penetrating peptides complex delivered siRNA efficiently and suppressed prostate tumor growth in vivo
Autor: | Mingquan Su, Hongyi Zhang, Xiaoke Hao, Jiayun Liu, Yueyun Ma, Yanjun Diao |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Male Cancer Research Aptamer Mice Nude Cell-Penetrating Peptides Biology Transfection 03 medical and health sciences Prostate cancer Mice 0302 clinical medicine In vivo RNA interference Cell Line Tumor medicine Animals Humans Amino Acid Sequence RNA Small Interfering Pharmacology Mice Inbred BALB C Prostatic Neoplasms medicine.disease Fusion protein Molecular biology 030104 developmental biology Oncology Lipofectamine 030220 oncology & carcinogenesis Biotinylation Cancer research Molecular Medicine Research Paper |
Zdroj: | Cancer biologytherapy. 17(5) |
ISSN: | 1555-8576 |
Popis: | Specific and efficient delivery of siRNA into intended tumor cells remains as a challenge, even though RNAi has been exploited as a new strategy for prostate cancer therapy. This work aims to address both specificity and efficiency of SURVIVIN-siRNA delivery by constructing a therapeutic complex using combinatorial strategies. A fusion protein STD was first expressed to serve as a backbone, consisting of streptavidin, a cell-penetrating peptide called Trans-Activator of Transcription (TAT) and a double-stranded RNA binding domain. A biotinylated Prostate Specific Membrane Antigen (PSMA) specific aptamer A10 and SURVIVIN-siRNA were then linked to STD protein to form the therapeutic complex. This complex could specifically targeted PSMA(+) tumor cells. Compared to lipofectamine and A10-siRNA chimera, it demonstrated higher efficiency in delivering siRNA into target cells by 19.2% and 59.9%, and increased apoptosis by 16.8% and 26.1% respectively. Upon systemic administration, this complex also showed significant efficacy in suppressing tumor growth in athymic mice (p |
Databáze: | OpenAIRE |
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