核酸、醫用奈米粒子組以及醫藥組合物

專利類型

發明

專利國別 (專利申請國家)

中華民國

專利申請案號

105137712

專利證號

I 607766

專利獲證名稱

核酸、醫用奈米粒子組以及醫藥組合物

專利所屬機關 (申請機關)

中原大學

獲證日期

2017/12/11

技術說明

本研究使用新型脂質磷酸鈣包覆EGFR 靜默RNA 後標靶到頭頸癌細胞抑制 EGFR 基因的表達， 本微脂體包覆新穎光敏劑藥物焦脫鎂葉氯甲酸 (pyropheophorbide、pyro) 並在微脂體表面上，接枝具標靶功用的大茴香醯胺 (anisamide) 使得微脂體具標靶能力可以標靶至口腔癌細胞，並以組合療法抑制 EGFR 基因的過表達及光動力治療之方式，共同毒殺腫瘤。本研究的LCP-EGFR siRNA 微脂體粒徑為34.9 ± 3.0.nm，表面電位為51.8 ± 1.8.mV；LCP-Pyro 微脂體 粒徑約為20 nm，表面電位為52.0 ± 7.6 mV。體外細胞實驗的目的找出最佳的組 合治療順序，以利提升頭頸癌細胞毒殺效果。經研究發現最佳毒殺細胞之順序組 合為先施以LCP-EGFR siRNA 抑制癌細胞的EGFR 表達量，再施以光動力治療， 在pyropheophorbide 濃度為0.25.μg/ml 結合LCP-EGFR siRNA 治療的頭頸癌細胞 存活率達80%，在西方墨點法亦證實於SCC4 及SAS 兩株口腔癌，分別抑制 89% 及97%的EGFR 蛋白質表達量。此細胞研究顯示先施以EGFR siRNA 抑制再施以 PDT 的組合治療確實可提升頭頸癌細胞毒殺功效。 EGFR siRNA was encapsulated into Lipid-calcium-phosphate nanoparticles (LCP NPs) to silence EGFR expression in head-and-neck squamous cell carcinoma (HNSCC). A novel photosensitizer, Pyropheophorbide, was modified with anisamide with LCP NPs. The above 2 treatments were combined for head-and-neck therapy in vitro and in vivo. The LCP-EGFR siRNA and LCP-Pyro particle sizes were 34.9 ± 3.0.nm and 20.nm respectively, zeta potential were 51.8 ± 1.8.mV and 52.0 ± 7.6.mV respectively. In vitro study, the combined therapy of LCP-EGFR siRNA + PDT was showed significantly greater inhibition response as decreased 80% of cell viability with pyro of 0.25 μg/ml in SCC4 and SAS cell lines. The western blot showed combined therapy has greater inhibition rate on SCC4 and SAS in vitro study at 89% and 97% respectively. These results indicated that the EGFR siRNA was effectively knocked down while PDT was successfully inhibited the cancer growth.

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