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靶向递送部分 VAR2CSA 肽导向 N-2-羟丙基三甲基氯化铵壳聚糖纳米粒用于多种癌症类型。

Targeting delivery of partial VAR2CSA peptide guided N-2-Hydroxypropyl trimethyl ammonium chloride chitosan nanoparticles for multiple cancer types.

机构信息

Engineering Research Center of Agricultural Microbiology Technology, Ministry of Education, Heilongjiang University, Harbin 150080, China; Key Laboratory of Microbiology, College of Heilongjiang Province, School of Life Science, Heilongjiang University, Harbin 150080, China.

Key Laboratory of Microbiology, College of Heilongjiang Province, School of Life Science, Heilongjiang University, Harbin 150080, China; Center for Reproduction and Health Development, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518052, China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2020 Jan;106:110171. doi: 10.1016/j.msec.2019.110171. Epub 2019 Sep 6.

Abstract

To developing a multiple cancer types targeting drug delivery carrier system, a 28 amino acids from the VAR2CSA was synthesized as the placental CSA-binding peptide (plCSA-BP). Its specific binding ability to cancer cells was tested on cancer tissue array, and the results showed that plCSA-BP could bind to multiple cancer types. Then, the plCSA-BP was used as a guiding peptide to coat nanoparticles synthesized from N-2-HACC (CSA/HACC-NPs) which were loaded with prodigiosin (CSA/HACC-PNPs) or indocyanine green (CSA/HACC-INPs). The cancer cells specific targeting and efficacy of the CSA/HACC-PNPs were tested by different cancer cells in vitro and various cancer xenograft model in vivo. A scramble peptide (SCR) was used as control and synthesized SCR/HACC-PNPs and SCR/HACC-INPs. The results showed that the CSA/HACC-INPs could specifically uptake by JEG-3, PC3 and A594 cells, and the CSA/HACC-PNPs exhibited better anti-cancer activity and lower toxic effect in subcutaneous choriocarcinoma and prostatic tumor models compared with the free prodigiosin, HACC-PNPs and SCR/HACC-PNPs. So, the CSA/HACC-NPs could be used as a specific delivery carrier for multiple cancer types, and provided an alternate treatment option of various cancers with a single recipe.

摘要

为了开发一种针对多种癌症类型的药物输送载体系统,我们合成了一段来自 VAR2CSA 的 28 个氨基酸作为胎盘 CSA 结合肽(plCSA-BP)。在癌症组织阵列上测试了其对癌细胞的特异性结合能力,结果表明 plCSA-BP 可以与多种癌症类型结合。然后,将 plCSA-BP 用作指导肽来包裹由 N-2-HACC(CSA/HACC-NPs)合成的纳米颗粒,该纳米颗粒负载有灵菌红素(CSA/HACC-PNPs)或吲哚菁绿(CSA/HACC-INPs)。通过体外不同癌细胞和体内各种癌症异种移植模型测试了 CSA/HACC-PNPs 的癌细胞特异性靶向和疗效。使用 scrambled peptide(SCR)作为对照,并合成了 SCR/HACC-PNPs 和 SCR/HACC-INPs。结果表明,CSA/HACC-INPs 可以特异性地被 JEG-3、PC3 和 A594 细胞摄取,与游离灵菌红素、HACC-PNPs 和 SCR/HACC-PNPs 相比,CSA/HACC-PNPs 在皮下绒癌和前列腺肿瘤模型中表现出更好的抗癌活性和更低的毒性作用。因此,CSA/HACC-NPs 可以作为多种癌症的特异性递送载体,为单一配方的多种癌症提供替代治疗选择。

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