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目的：优化制备K237 多肽修饰的紫杉醇隐形纳米粒(K237-PTX-NP)，并评价其对HCT-15 和HUVEC 两种细胞的细胞毒性。方法：乳化- 溶剂挥发法优化制备K237-PTX-NP；HPLC 法测定其包封率、载药量；激光粒度分析仪测定其粒径和Zeta 电位； CBQCA 试剂盒测定纳米粒表面多肽密度。以Taxol 和PTX-NP 为对照，采用CCK-8 方法研究比较K237-PTX-NP 对HCT-15 和 HUVEC 细胞的细胞毒性差异。结果：优化制备的K237-PTX-NP 粒径为约150 nm，Zeta 电位为-20 mv，包封率为33.5 %，载药量为2.8 %，多肽连接效率为24.5 %，平均每个纳米粒表面连接的K237 数目约为474 个。作用24 h 时，K237-PTX-NP 抑制HUVEC 活性的IC50 为0.01 nM，而抑制HCT-15 活性的IC50 大于1 μM。结论：与HCT-15 相比，HUVEC 对K237-PTX-NP 高度敏感，提示 K237-PTX-NP 具有潜在通过抑制肿瘤血管内皮细胞的生长治疗以HCT-15 为代表的、P-gp 等膜转运蛋白高表达的耐药肿瘤的能力。

英文摘要:

Objective: To optimize paclitaxel-loaded stealth nanoparticles decorated with K237 peptides (K237-PTX-NP) and evaluate the cytotoxicity to HCT-15 and HUVEC cells. Methods: Paclitaxel-loaded stealth nanoparticles decorated with K237 peptides (K237-PTX-NP) were prepared by emulsification-evaporation method. The encapsulation efficiency and drug loading were determined by HPLC. The particle sizes, polydispersity, zeta potential were measured by dynamic light scattering assay. K237 density on the nanoparticle surface was determined by CBQCA Protein Quantitation Kit. With Taxol and PTX-NP as control, the cytotoxicity of K237-PTX-NP to HCT-15 and HUVEC were determined using CCK-8 assay. Results: The average partic1e size of K237-PTX-NP was 150 nm. The zeta potential was -20 mV; Encapsulating efficiency was 33.5 %; Drug loading was 2.8 %, K237 conjuation efficiency was 24.5 % and K237 density on the nanoparticle surface was 474. After 24 h incubation, the IC50 values of K237-PTX-NP for HUVEC and HCT-15 cells were about 0.01 nM and over 1 μM respectively. Conclusion: Compared with HCT-15 cells, HUVEC cells are much more sensitive to K237-PTX-NP, which suggested that K237-PTX-NP may have the capacity to treat multidrug resistant tumors like HCT-15, and it was highly expressed with P-gp or other multidrug resistance associated proteins, through inhibiting the growth of tumor endothelial cells.

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