Screening of novel RGD peptides to modify nanoparticles for targeted cancer therapy
Screening of novel RGD peptides to modify nanoparticles for targeted cancer therapy
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筛选新型 RGD 肽以修饰纳米粒子用于靶向癌症治疗
DOI：
10.1039/c7bm00776k
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发表时间：
2017-01-01
影响因子：
6.6
通讯作者：
Qian, Hai
中科院分区：
文献类型：
--
作者：
Ge, Liang;You, Xinru;Qian, Hai
利用分子操作环境（莫伊）筛选了固相肽合成（SPPS）法合成的新型靶向RGD肽，并将其用于6-O-羧甲基壳聚糖载体的构建。以合成的载体为载体，采用离子凝胶法制备了CRGDYC-6-O-羧甲基壳聚糖纳米粒。通过测定纳米粒的粒径和药物包封率，优化了纳米粒的合成条件和处方参数。6-O-羧甲基壳聚糖浓度、氯化钙浓度和氯化钙/6-O-羧甲基壳聚糖比例均对药物的粒径和包封率有影响。在最佳处方条件下，成功制备了平均粒径为193.4nm、平均载药量为0.395%、平均载药量为69.5%的纳米粒。流式细胞术和共聚焦显微镜分析表明，与未修饰的纳米颗粒相比，CRGDYC修饰的纳米颗粒在人乳腺癌细胞系（MCF-7）中对DOX的细胞摄取更高。体内成像显示，与未修饰的纳米颗粒相比，CRGDYC修饰的纳米颗粒在肿瘤部位的分布更高。这些结果表明，CRGDYC-6-O-羧甲基壳聚糖可能是一种有前途的肿瘤靶向载体，可以提高载药纳米粒的细胞内摄取和细胞毒性。
New targeted RGD peptides obtained by solid phase peptide synthesis (SPPS) were successfully screened by Molecular Operating Environment (MOE) and used for the building of the 6-O-carboxymethyl chitosan based carrier with an active target on the surface. CRGDYC-6-O-carboxymethyl chitosan based nanoparticles (NPs) loaded with doxorubicin hydrochloride (DOX) were successfully prepared by an ionic gelation method with the carrier synthesized before. Synthesis conditions and formulation parameters were optimized by determining the characteristics of nanoparticles including the particle size and drug encapsulation efficiency. 6-O-Carboxymethyl chitosan concentration, calcium chloride concentration and calcium chloride/6-O-carboxymethyl chitosan ratio all had effects on the particle size and drug encapsulation efficiency. Nanoparticles with an average diameter of 193.4 nm, an average drug loading efficiency of up to 69.5% and an average drug loading of up to 0.395% were prepared successfully with the optimal formulation. Flow cytometry and confocal microscopy analyses showed that the cellular uptake of DOX in human breast cancer cell lines (MCF-7) was higher in the CRGDYC-modified nanoparticles compared with the unmodified nanoparticles. In vivo imaging showed that the distribution of CRGDYC-modified nanoparticles in the tumor site was higher compared with the unmodified nanoparticles. These results suggest that CRGDYC-6-O-carboxymethyl chitosan may be a promising cancer targeting carrier which can enhance the intracellular uptake and cytotoxicity of the drug-loaded nanoparticles.