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Improvement of Gene Silencing and Development of siRNA Delivery by Dendritic Gold Nanoparticle
김다훤,임수연,정재백,김동민,조희주,정지훈 한국공업화학회 2020 한국공업화학회 연구논문 초록집 Vol.2020 No.-
Small interfering RNA (siRNA) delivery system has been a therapeutic strategy in RNA interference (RNAi) by sequence-specifically silencing target gene. However, a rigid double-stranded structure of siRNA limits the formation of tight complex with conventional cationic carriers. Therefore, stabilization of siRNA/carrier complexes is a prerequisite for an efficient siRNA delivery. In this study, we synthesized dendritic gold nanoparticles (Au@MCs) by using polymeric micelles. Ionic interaction and physical interaction with Au@MCs stabilized the encapsulation of siRNA. As a result, the siRNA/Au@MCs contributed to serum stability and improved gene silencing effect.
Suppresion of Tumor Growth via Systemic siRNA Delivery with Reducible Bile Acid-conjugated PEI
김다훤,임수연,정재백,김동민,조희주,정지훈 한국공업화학회 2020 한국공업화학회 연구논문 초록집 Vol.2020 No.-
Small interfering RNA (siRNA) delivery has been considered as a potential cancer therapy because it contributes to RNA interference (RNAi). In this study, we synthesized a conjugate of low molecular weight polyethylnimine (PEI, 1.8 kDa) and deoxycholic acid (DA). A DA-PEI conjugate was further modified with 4-fluorothiophenol (FTP) (TP-DA-PEI) to enhance systemic siRNA delivery. The thiophenol group would be involved with disulfide bonds between the polymer chains and siRNA modified with free thiols (thiol-siRNA) to form and π -π interactions between the pendent aromatic groups and coprostane ring of the bile acid. The stabilization of TP-DA-PEI conjugate with thiol-siRNA enhanced intracellular uptake, serum stability, and transfection efficiency. Moreover, it showed high intratumoral accumulation of TP-DA-PEI/thiol-siRNA polyplexes and significant tumor growth inhibition effect in a murine tumor model after systemic administration.
Reducible Bile Acid-Modified PEI Enhances Systemic siRNA Delivery and Inhibits Tumor Growth
김다훤,정지훈,( Yin Yue ),정재백 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.0
RNA interference (RNAi), mediated by small interfering RNA (siRNA), has been considered as a potential therapeutic agent for cancer owing to its ability to suppress target genes in a sequence-specific manner. However, the inherent susceptibility of siRNA to degradation by nucleases in the blood and its poor cellular uptake have been considered major challenges for the clinical use of the systemic siRNA therapy. Therefore, an effective and stable systemic siRNA delivery system should be established. 4-fluorothiophenol-deoxycholic acid-polyethylenimine conjugates could generate stable nanoparticles with thiol-siRNA. The conjugates showed significant tumor growth inhibition effect in tumor-bearing mice after systemic administration. Therefore, the synthesized conugates could be considered as a candidate carrier for systemic cancer therapy using siRNA therapeutics.
Systemic siRNA Delivery with Reducible Bile Acid-Modified PEI for Cancer Therapy
김다훤,임수연,김이슬,정재백,김동민,조희주,정지훈 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.1
Small interfering RNA (siRNA) delivery has been considered as a potential cancer therapy because it contributes to RNA interference (RNAi) by inhibiting target gene expression in a sequence-specific manner. In this study, low molecular weight polyethylnimine (PEI, 1.8 kDa) was conjugated with deoxycholic acid (DA). A DA-PEI conjugate was further modified with 4-fluorothiophenol (FTP) (TP-DA-PEI) to enhance systemic siRNA delivery. The thiophenol group would be involved with disulfide bonds between the polymer chains and siRNA modified with free thiols (thiol-siRNA) to form and π-π interactions between the pendent aromatic groups and coprostane ring of the bile acid. The stabilized TP-DA-PEI conjugate with thiol-siRNA achieved enhanced intracellular uptake, serum stability, and transfection efficiency. In addition, it showed high accumulation of TP-DA-PEI/ thiol-siRNA polyplexes and significant tumor growth inhibition effect in tumor-bearing mice after systemic administration.
Application of Dendritic Gold Nanoparticle for Efficient siRNA Delivery System and Gene Silencing
김다훤,임수연,김이슬,정재백,김동민,조희주,정지훈 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.1
Small interfering RNA (siRNA) delivery system has been one of therapeutic strategies in RNA interference (RNAi) by sequence-specifically silencing target gene. However, a rigid double-stranded structure of siRNA hinders the formation of tight complex with conventional cationic carriers. Therefore, stabilized siRNA/carrier complexes are required to support an efficient siRNA delivery. In this study, dendritic gold nanoparticles (Au@MCs) were synthesized by using polymeric micelles. The stable encapsulation of siRNA was enhanced both by ionic interaction and physical interaction with Au@MCs. As a result, the siRNA/Au@MCs contributed to serum stability and improved gene silencing effect.