自组装短肽RAD16-Ⅰ构建抗肿瘤药物原位水凝胶的初步研究Δ

摘要

OBJECTIVE:To investigate the possibility of constructing anti-cancer drug in-situ hydrogel with self-assembling peptide RAD16-Ⅰ. METHODS:The rheological parameters as storage modulus(G′),loss modulus(G″)and phase angle(Δ)of 0.1%,0.2% and 0.5% RAD16-Ⅰ solution containing paclitaxel or not were determined by rheometer before and after mixing with isometric phosphate buffer solution (PBS);RAD16-Ⅰ solution containing paclitaxel or not were mixed with breast cancer MDA-MB-435S cells culture medium to obtain hydrogel,the status and effect of which on cell morphology were observed by in-verted microscope (compared with paclitaxel solution). RESULTS:In RAD16-Ⅰ solution containing paclitaxel or not,G′was close to or slightly higher than G″,and G′and G″had changed slightly as the concentration of peptide increased. Compared with not mixed with PBS,G′increased significantly in concentration-dependent manner after mixed with PBS,and G″also increased but was slighter than G′;Δ decreased significantly. In cell culture media,RAD16-Ⅰ solutions containing paclitaxel could form hy-drogel and maintain their gel form,cancer cells kept same morphology after treated with hydrogel and same concentration of pacli-taxel solution for same time. CONCLUSIONS:RAD16-Ⅰ solutions containing paclitaxel can form hydrogel under simulated physi-ological conditions,which can maintain their gel form and have anti-cancer effect of paclitaxel.%目的：探索自组装短肽RAD16-Ⅰ构建抗肿瘤药物原位水凝胶的可能性。方法：采用流变仪测量含与不含抗肿瘤药物紫杉醇的0.1％、0.2％、0.5％RAD16-Ⅰ水溶液与等体积的磷酸盐缓冲液（PBS）混合前后的储存模量（G′）、损耗模量（G″）、相位角（Δ）等流变学参数；通过倒置显微镜观察含与不含紫杉醇的RAD16-Ⅰ水溶液加入乳腺癌MDA-MB-435S细胞的培养基后形成的水凝胶状态及对细胞形态的影响（与紫杉醇水溶液比较）。结果：在含与不含紫杉醇的RAD16-Ⅰ水溶液中，G′近似或略大于G″，随RAD16-Ⅰ浓度增加G′和G″变化很小；与不加PBS比较，加入PBS后G′显著增加且呈浓度依赖性，G″也有增加但增加幅度比G′要小很多，Δ显著变小。含紫杉醇的RAD16-Ⅰ溶液在细胞培养基中能形成并保持水凝胶状态，水凝胶与同浓度紫杉醇水溶液作用于细胞相同时间后的细胞形态基本相同。结论：含紫杉醇的RAD16-Ⅰ水溶液可在模拟生理条件下形成水凝胶，并保持凝胶状态和紫杉醇固有的抗肿瘤作用。