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基于短芳香族肽的酸敏感纳米纤维缀合物用于肝癌的多柔比星靶向递送

An Acid-Sensitive Nanofiber Conjugate Based on a Short Aromatic Peptide for Targeted Delivery of Doxorubicin in Liver Cancer.

机构信息

School of Chemical Engineer and Pharmacy, Henan University of Science and Technology, Luoyang, People's Republic of China.

School of Basic Medical Sciences, Henan University of Science and Technology, Luoyang, People's Republic of China.

出版信息

Int J Nanomedicine. 2022 Jul 5;17:2961-2973. doi: 10.2147/IJN.S359642. eCollection 2022.

DOI:10.2147/IJN.S359642
PMID:35818401
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9270908/
Abstract

PURPOSE

This study aimed to construct a DOX conjugate with liver tumor targeting and acid sensitivity based on a short aromatic peptide FFYEE, which could amplify the tumor inhibition efficacy of DOX and alleviate tissue toxicity.

METHODS

A novel DOX-peptide conjugate, D-gal-FFYEE-hyd-DOX, was constructed by linking DOX to the side chain of FFYEE with acid-sensitive hydrazone bond and by modifying the C-terminal of peptide with α-D-galactosamine (D-gal) as targeting ligand. The structure of D-gal-FFYEE-hyd-DOX was characterized by mass spectrometry, infrared spectroscopy (IR), and UV-Vis spectroscopy (UV-Vis). The assembly characteristics of pentapeptide FFYEE and D-gal-FFYEE-hyd-DOX were observed by transmission electron microscope (TEM). In vitro drug release, cytotoxicity, endocytosis, in vivo antitumor experiment and histopathology analysis were investigated.

RESULTS

Peptide FFYEE endowed the D-gal-FFYEE-hyd-DOX with self-assembly performance and improved biocompatibility. D-gal-FFYEE-hyd-DOX can self-assemble into nanofibers with a diameter of ~ 40 nm in neutral aqueous solution and significantly reduced the cytotoxicity of free DOX to L02 cells. In vitro drug release results showed that D-gal-FFYEE-hyd-DOX had acid sensitivity and controlled release characteristics. The cytotoxicity and endocytosis investigations confirmed that D-gal-FFYEE-hyd-DOX enhanced the cellular uptake of DOX and inhibition effect on HepG2 cells. In vivo antitumor experiment indicated that D-gal-FFYEE-hyd-DOX could significantly inhibit the growth of liver tumor in mice and reduce the side effects of DOX.

CONCLUSION

The conjugate D-gal-FFYEE-hyd-DOX with liver tumor targeting and acid sensitivity has the characteristics of strong tumor inhibition and low toxicity, hinting the great clinical application potential for targeted delivery of DOX in cancer treatment.

摘要

目的

本研究旨在构建一种基于短芳香肽 FFYEE 的具有肝肿瘤靶向和酸敏感性的 DOX 缀合物，以增强 DOX 的肿瘤抑制作用并减轻组织毒性。

方法

通过将 DOX 与 FFYEE 的侧链通过酸敏感的腙键连接，并通过将肽的 C 末端修饰为α-D-半乳糖胺（D-gal）作为靶向配体，构建了一种新型 DOX-肽缀合物 D-gal-FFYEE-hyd-DOX。通过质谱、红外光谱（IR）和紫外可见光谱（UV-Vis）对 D-gal-FFYEE-hyd-DOX 的结构进行了表征。通过透射电子显微镜（TEM）观察五肽 FFYEE 和 D-gal-FFYEE-hyd-DOX 的组装特性。考察了 D-gal-FFYEE-hyd-DOX 的体外药物释放、细胞毒性、内吞作用、体内抗肿瘤实验和组织病理学分析。

结果

肽 FFYEE 赋予 D-gal-FFYEE-hyd-DOX 自组装性能和提高的生物相容性。D-gal-FFYEE-hyd-DOX 可以在中性水溶液中自组装成直径约为 40nm 的纳米纤维，并显著降低游离 DOX 对 L02 细胞的细胞毒性。体外药物释放结果表明，D-gal-FFYEE-hyd-DOX 具有酸敏感性和控制释放特性。细胞毒性和内吞作用研究证实，D-gal-FFYEE-hyd-DOX 增强了 DOX 的细胞摄取和对 HepG2 细胞的抑制作用。体内抗肿瘤实验表明，D-gal-FFYEE-hyd-DOX 可显著抑制小鼠肝肿瘤的生长，降低 DOX 的副作用。

结论

具有肝肿瘤靶向和酸敏感性的缀合物 D-gal-FFYEE-hyd-DOX 具有较强的肿瘤抑制作用和低毒性，提示其在癌症治疗中 DOX 靶向递送上具有巨大的临床应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a920/9270908/2e8e3f25d585/IJN-17-2961-g0011.jpg
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本文引用的文献

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2
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3
Research progress in strategies to improve the efficacy and safety of doxorubicin for cancer chemotherapy.阿霉素用于癌症化疗的疗效和安全性提高策略的研究进展。
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Int J Mol Sci. 2023 Feb 27;24(5):4590. doi: 10.3390/ijms24054590.
Expert Rev Anticancer Ther. 2021 Dec;21(12):1385-1398. doi: 10.1080/14737140.2021.1991316. Epub 2021 Nov 1.
4
Design and application of hybrid cyclic-linear peptide-doxorubicin conjugates as a strategy to overcome doxorubicin resistance and toxicity.杂环线性肽-阿霉素缀合物的设计与应用：克服阿霉素耐药性和毒性的策略。
Eur J Med Chem. 2021 Dec 15;226:113836. doi: 10.1016/j.ejmech.2021.113836. Epub 2021 Sep 10.
5
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6
Role of acetylation in doxorubicin-induced cardiotoxicity.乙酰化在阿霉素致心肌毒性中的作用。
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7
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