壳聚糖与细胞穿透肽共修饰的纳米粒制备及抗结肠癌的体外细胞学评价

Preparation of nanoparticles co-modified with chitosan and cell-penetrating peptides and in vitro cytological evaluation against colon cancer

目的:为了提高5-氟尿嘧啶(5-FU)抗结肠癌的口服疗效,构建了一种由N,N,N-三甲基-N-硬脂酰壳聚糖(TSCS)、腺苷和细胞穿透肽(TAT)共修饰的聚乳酸-羟基乙酸共聚物(PLGA)纳米粒,并对其进行相关评价。方法:合成TSCS、硬脂酰腺苷与5-FU磷脂复合物,制备了腺苷穿透肽共修饰纳米粒(AD-CPP-NPs),并对其进行粒径、包封率、体外释放等药剂学和细胞学评价。结果:纳米粒外观为类球形,分布均一。测得纳米粒粒径约为177 nm,Zeta电位为38.2 mV,包封率为56.6%。细胞实验表明,与HT-29细胞共孵育4 h后,与表面未修饰的PLGA纳米粒相比,共修饰纳米粒摄取能力相对聚乙烯醇纳米粒提高16.42倍。结论:共修饰纳米粒能主动靶向结肠癌细胞、增强细胞摄取效率、增加5-FU在癌细胞内的蓄积。

Objective:To improve the oral efficacy of 5-fluorouracil(5-FU)against colon cancer,PLGA nanoparticles co-modified by N,N,N-trimethyl-N-stearoyl chitosan(TSCS),adenosine and cell-penetrating peptide(TAT)were constructed and evaluated.Methods:TSCS,stearoyl adenosine and 5-fluorouracil phospholipid complexes were synthesized and co-modified nanoparticles AD-CPP-NPs were prepared and evaluated pharmacologically and cytologically in terms of particle size,encapsulation rate and in vitro release.Results:The nanoparticles were sphere-like in appearance and homogeneously distributed.The measured nanoparticle size was about 177 nm,the Zeta potential was 38.2 mV,and the encapsulation rate was 56.6%.Cellular experiments showed that after coincubation with HT-29 cells for 4 h,the uptake capacity of co-modified nanoparticles was increased by 16.42-fold relative to PVA-NPs compared to PLGA nanoparticles with unmodified surface.Conclusion:Co-modified nanoparticles can actively target colon cancer cells,enhance cell uptake efficiency,and increase the accumulation of 5-FU in cancer cells.