N-琥珀酰壳聚糖纳米粒肿瘤靶向性及抗肿瘤活性评价

目的评价N-琥珀酰壳聚糖纳米粒（Suc-Chi/NPs）肿瘤靶向性,考察5-氟尿嘧啶-N-琥珀酰壳聚糖纳米粒（5-FU-Suc-Chi/NPs）抗肿瘤活性。方法建立异硫氰基荧光素（FITC）-Suc-Chi/NPs的体内荧光分析方法,检测Suc-Chi/NPs在Sarcoma 180-荷瘤小鼠体内组织分布数量。采用荧光显微镜观察FICT-Suc-Chi/NPs在组织切片中蓄积量,评价FICT-Suc-Chi/NPs肿瘤靶向性;以Suc-Chi/NPs、5-FU注射液为对照,考察5-FU-Suc-Chi/NPs在Sarcoma 180-荷瘤小鼠体内的瘤体积抑制率及对荷瘤小鼠体重的影响,评价制剂的疗效及不良反应。结果 FICT-Suc-Chi/NPs能够长时间的滞留在血液中,在各组织及血浆中分布的数量次序依次为肾〉肿瘤〉血液〉肝〉脾〉肺。5-FU-Suc-Chi/NPs与5-FU注射液相比较,能够更有效地抑制Sarcoma 180肿瘤的生长,而且组织毒性较温和。结论研究表明N-琥珀酰壳聚糖纳米粒具有长循环特性,能够实现实体肿瘤靶向传递;以N-琥珀酰壳聚糖为载体包载抗肿瘤模型药纳米粒具有较高抗肿瘤活性及较低的毒性。

Evaluation for Tumor Targeting and Anti-Tumor Activity of N-Succinyl-Chitosan Nanoparticles

OBJECTIVE To investigate the tumor targeting of N-Succinyl-Chitosan(Suc-Chi) nanoparticles (Suc-Chi/NPs) and the anti-tumor activity of 5-fluorouracil loaded Suc-Chi/NPs (5-Fu-Suc-Chi/NPs). METHODS The distributed amount of FITC-Suc-Chi/NPs in tissues and blood of Sarcoma 180-bearing mice was estimated by the fluorescence measurement. These observations were further confirmed by fluorescence microscopy results of the tissues sections. The anti-tumor activity and toxicity of 5-FU-Suc-Chi-NPs were evaluated by measuring the change in the tumor volume and body weight of Sarcoma 180-bearing mice after intravenous injection of Suc-Chi/NPs, 5-FU-Suc-Chi/NPs, and 5-FU. RESULTS The Suc-Chi/NPs could be sustained in blood throughout a very long time, the rank order of tissue distribution was kidney>tumor>blood>liver>spleen>lung. The 5-FU-Suc-Chi/NPs showed good antitumour activities against Sarcoma 180 solid tumour and mild toxicity, compared with 5-FU injections. CONCLUSION The results revealed that Suc-Chi/NPs were accumulated in the tumor tissue due to the EPR effect and its long systemic retention in blood circulation. The anti-tumor model drug loaded Suc-Chi/NPs showed good antitumour activities against solid tumour and mild toxicity.