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Matrix metalloprotein-triggered, cell penetrating peptide-modified star-shaped nanoparticles for tumor targeting and cancer therapy
Journal of Nanobiotechnology ( IF 10.6 ) Pub Date : 2020-03-17 , DOI: 10.1186/s12951-020-00595-5
Fangyuan Guo , Qiafan Fu , Kang Zhou , Chenghao Jin , Wenchao Wu , Xugang Ji , Qinying Yan , Qingliang Yang , Danjun Wu , Aiqin Li , Gensheng Yang

Specific targeting ability and good cell penetration are two critical requirements of tumor-targeted delivery systems. In the present work, we developed a novel matrix metalloprotein-triggered, cell-penetrating, peptide-modified, star-shaped nanoparticle (NP) based on a functionalized copolymer (MePEG-Peptide-Tri-CL), with the peptide composed of GPLGIAG (matrix metalloprotein-triggered peptide for targeted delivery) and r9 (cell-penetrating peptide for penetration improvement) to enhance its biological specificity and therapeutic effect. Based on the in vitro release study, a sustained release profile was achieved for curcumin (Cur) release from the Cur-P-NPs at pH 7.4. Furthermore, the release rate of Cur was accelerated in the enzymatic reaction. MTT assay results indicated that the biocompatibility of polymer NPs (P-NPs) was inversely related to the NP concentration, while the efficiency toward tumor cell inhibition was positively related to the Cur-P-NP concentration. In addition, Cur-P-NPs showed higher fluorescence intensity than Cur-NPs in tumor cells, indicating improved penetration of tumor cells. An in vivo biodistribution study further demonstrated that Cur-P-NPs exhibited stronger targeting to A549 xenografts than to normal tissue. Furthermore, the strongest tumor growth inhibition (76.95%) was observed in Cur-P-NP-treated A549 tumor xenograft nude mice, with slight pulmonary toxicity. All results demonstrated that Cur-P-NP is a promising drug delivery system that possesses specific enzyme responsiveness for use in anti-tumor therapy.

中文翻译:

基质金属蛋白触发的细胞穿透肽修饰的星形纳米颗粒,用于肿瘤靶向和癌症治疗

特异性靶向能力和良好的细胞渗透性是靶向肿瘤的递送系统的两个关键要求。在目前的工作中,我们基于功能化共聚物(MePEG-Peptide-Tri-CL)开发了一种新型基质金属蛋白触发的,可穿透细胞的,肽修饰的星形纳米颗粒(NP),该肽由GPLGIAG组成(基质金属肽触发肽用于靶向递送)和r9(细胞穿透肽用于渗透性改善),以增强其生物学特异性和治疗效果。根据体外释放研究,在pH 7.4下,姜黄素(Cur)从Cur-P-NPs释放的缓释曲线得以实现。此外,在酶促反应中,Cur的释放速度加快。MTT分析结果表明,聚合物NPs(P-NPs)的生物相容性与NP浓度成反比,而抑制肿瘤细胞的效率与Cur-P-NP浓度成正比。另外,Cur-P-NP在肿瘤细胞中显示出比Cur-NP更高的荧光强度,表明肿瘤细胞的渗透性提高。体内生物分布研究进一步表明,与正常组织相比,Cur-P-NP对A549异种移植物的靶向作用更强。此外,在经Cur-P-NP处理的A549肿瘤异种移植裸鼠中观察到最强的肿瘤生长抑制作用(76.95%),具有轻微的肺毒性。所有结果表明,Cur-P-NP是一种有前途的药物输送系统,具有用于抗肿瘤治疗的特异性酶反应性。而抑制肿瘤细胞的效率与Cur-P-NP浓度呈正相关。另外,Cur-P-NP在肿瘤细胞中显示出比Cur-NP更高的荧光强度,表明肿瘤细胞的渗透性提高。体内生物分布研究进一步表明,与正常组织相比,Cur-P-NP对A549异种移植物的靶向作用更强。此外,在经Cur-P-NP处理的A549肿瘤异种移植裸鼠中观察到最强的肿瘤生长抑制作用(76.95%),具有轻微的肺毒性。所有结果表明,Cur-P-NP是一种有前途的药物输送系统,具有用于抗肿瘤治疗的特异性酶反应性。而抑制肿瘤细胞的效率与Cur-P-NP浓度呈正相关。另外,Cur-P-NP在肿瘤细胞中显示出比Cur-NP更高的荧光强度,表明肿瘤细胞的渗透性提高。体内生物分布研究进一步表明,与正常组织相比,Cur-P-NP对A549异种移植物的靶向作用更强。此外,在经Cur-P-NP处理的A549肿瘤异种移植裸鼠中观察到最强的肿瘤生长抑制(76.95%),并具有轻微的肺毒性。所有结果表明,Cur-P-NP是一种有前途的药物输送系统,具有用于抗肿瘤治疗的特异性酶反应性。表明肿瘤细胞的渗透性提高。体内生物分布研究进一步证明,与正常组织相比,Cur-P-NP对A549异种移植物的靶向作用更强。此外,在经Cur-P-NP处理的A549肿瘤异种移植裸鼠中观察到最强的肿瘤生长抑制作用(76.95%),并具有轻微的肺毒性。所有结果表明,Cur-P-NP是一种有前途的药物输送系统,具有用于抗肿瘤治疗的特异性酶反应性。表明肿瘤细胞的渗透性提高。体内生物分布研究进一步表明,与正常组织相比,Cur-P-NP对A549异种移植物的靶向作用更强。此外,在经Cur-P-NP处理的A549肿瘤异种移植裸鼠中观察到最强的肿瘤生长抑制作用(76.95%),具有轻微的肺毒性。所有结果表明,Cur-P-NP是一种有前途的药物输送系统,具有用于抗肿瘤治疗的特异性酶反应性。
更新日期:2020-04-22
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