A polymeric nanocarrier with a tumor acidity-activatable arginine-rich (R9) peptide for enhanced drug delivery.,Biomaterials Science

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A polymeric nanocarrier with a tumor acidity-activatable arginine-rich (R9) peptide for enhanced drug delivery.
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-02-21 , DOI: 10.1039/d0bm00069h
Liting Zhang ₁ , Chengtao Jiang ₁ , Fanjun Zeng ₂ , Haiyu Zhou ₂ , Dongdong Li ₃ , Xinyu He ₄ , Song Shen ₅ , Xianzhu Yang ₆ , Jun Wang ₇

Affiliation

Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, P. R. China. and Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, P. R. China.
Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P. R. China.
Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, P. R. China and Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou 510006, P. R. China.
Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, P. R. China. and Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, P. R. China and Key Laboratory of Biomedical Engineering of Guangdong Province, and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, P. R. China.
School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 510006, P. R. China.
Institutes for Life Sciences, School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, P. R. China.
Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510006, P. R. China. and School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 510006, P. R. China and Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou 510005, P.R. China.

Cell-penetrating peptides (CPPs) have been considered as a powerful tool to improve the intracellular and nuclear delivery efficiency of nanocarriers. However, their clinical application is limited because of their nonspecific targeting function, short half-life, and severe system toxicity. Herein, we have developed a polymeric nanocarrier with a tumor acidity-activatable arginine-rich (R9) peptide for targeted drug delivery. The nanocarrier is fabricated with a R9-conjugated amphiphilic diblock polymer of poly(ethylene glycol) (PEG) and poly(hexyl ethylene phosphate) (PHEP), and then further coated with tumor acidity-activatable polyanionic polyphosphoester through electrostatic interaction in order to block the nonspecific targeting function of the R9 peptide. In the slightly acidic tumor extracellular environment (∼pH 6.5), tumor acidity-activatable polyanionic polyphosphoester would be deshielded from the nanoparticles, resulting in the re-exposure of the R9 peptide to enhance tumor cellular uptake. As a result, intracellular concentration of payload in 4T1 tumor cells significantly increased at pH 6.5. And, we further demonstrate that such a delivery system remarkably promoted the anti-tumor efficiency of chemotherapeutic drugs in tumor-bearing mice, offering great potential for drug delivery and cancer therapy.

中文翻译：

具有肿瘤酸性可激活的富含精氨酸（R9）肽的聚合物纳米载体，可增强药物的递送。

细胞穿透肽（CPPs）被认为是提高纳米载体细胞内和核内递送效率的强大工具。但是，由于其非特异性靶向功能，半衰期短和严重的系统毒性，其临床应用受到限制。在这里，我们已经开发了具有肿瘤酸性可激活的富含精氨酸（R9）肽的聚合物纳米载体，用于靶向药物递送。纳米载体由聚乙二醇（PEG）和聚己基磷酸乙二酯（PHEP）的R9共轭两亲性二嵌段聚合物制成，然后通过静电相互作用进一步涂覆有肿瘤酸性可活化的聚阴离子聚磷酸酯，以阻止R9肽的非特异性靶向功能。在微酸性肿瘤细胞外环境（pH 6.5）下，肿瘤酸性可活化的聚阴离子聚磷酸酯将从纳米颗粒上脱开，从而使R9肽重新暴露以增强肿瘤细胞的摄取。结果，在pH 6.5下4T1肿瘤细胞中有效载荷的细胞内浓度显着增加。并且，我们进一步证明，这种递送系统显着提高了荷瘤小鼠中化疗药物的抗肿瘤效率，为药物递送和癌症治疗提供了巨大潜力。

更新日期：2020-02-21

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