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目的 合成叶酸介导靶向的聚乳酸共聚物,以其为靶向膜材制备靶向造影剂,表征造影剂性质。方法 以自制的叶酸-脯氨酸-乳酸共聚物(Fa-PLLA-Hpr)为膜材,应用双乳化-冷冻干燥法制备叶酸介导靶向高分子造影剂(MB-Fa-PLLA)。采用激光粒径测量仪检测微泡的粒径,通过光镜观察该靶向造影剂(靶向造影剂实验组)对人卵巢癌SKOV3细胞的体外寻靶情况,并与游离叶酸干预组及空白对照组(普通微泡)比较。结果 FT-IR表征了靶向膜材的结构。成功制备叶酸介导靶向聚乳酸共聚物MB-Fa-PLLA。MB-Fa-PLLA在光镜下大小分布均匀,形态圆整,65%的微粒直径分布为500~800nm,呈单峰分布,其亲水性较普通高分子微泡更好。体外寻靶实验显示,MB-Fa-PLLA可以较多并牢固地聚集到SKOV3细胞表面,而普通微泡未见特异性结合。结论 MB-Fa-PLLA亲水性好,对高表达叶酸受体的SKOV3细胞具有较强特异性亲合力,其有望成为靶向显像叶酸高表达肿瘤的理想造影剂。
OBJECTIVE: To synthesize folate-mediated polylactic acid copolymer and use it as targeted membrane to prepare targeted contrast medium and characterize contrast medium. Methods Folic acid-mediated targeted polymeric contrast agent (MB-Fa-PLLA) was prepared by double-emulsion-freeze drying method using self-made folate-proline-lactic acid copolymer (Fa-PLLA- The particle size of microbubbles was detected by laser particle size analyzer. The targeted contrast agent (targeting contrast agent experimental group) was used to observe the in vitro targeting of human ovarian cancer cell line SKOV3 by light microscope, and compared with free folic acid intervention group and blank Control group (normal microbubbles) comparison. Results FT-IR characterizes the structure of the targeted membrane. Folate-mediated targeted polylactic acid copolymer MB-Fa-PLLA was successfully prepared. MB-Fa-PLLA was uniform in size and uniform in shape under light microscope. The diameter of 65% of the particles was distributed between 500 and 800 nm with a monomodal distribution. The hydrophilicity of MB-Fa-PLLA was better than that of ordinary polymer microbubbles. In vitro targeting experiments showed that MB-Fa-PLLA could accumulate more and firmly on the surface of SKOV3 cells, but no specific binding was found on normal microbubbles. Conclusion MB-Fa-PLLA has good hydrophilicity and strong affinity to SKOV3 cells with high expression of folate receptor, which is expected to be an ideal contrast agent for targeted imaging of folate-overexpressing tumors.