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探索天然存在的常春藤纳米颗粒作为一种替代生物材料。

Exploring naturally occurring ivy nanoparticles as an alternative biomaterial.

作者信息

Huang Yujian, Wang Yi-Jun, Wang Yongzhong, Yi Sijia, Fan Zhen, Sun Leming, Lin Derrick, Anreddy Nagaraju, Zhu Hua, Schmidt Michael, Chen Zhe-Sheng, Zhang Mingjun

机构信息

Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, USA; Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA; Interdisciplinary Biophysics Graduate Program, The Ohio State University, Columbus, OH 43210, USA.

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.

出版信息

Acta Biomater. 2015 Oct;25:268-83. doi: 10.1016/j.actbio.2015.07.035. Epub 2015 Jul 26.

DOI:10.1016/j.actbio.2015.07.035
PMID:26219859
Abstract

UNLABELLED

Arabinoglactan protein (AGP)-rich nanoparticles obtained from the sticky exudates of Hedera helix (English ivy), have shown promising potential to be used in nanomedicine owing to their excellent aqueous solubility, low intrinsic viscosity, biocompatibility, and biodegradability. In this study, the feasibilities of utilizing ivy nanoparticles (INPs) as nano-carriers for delivering chemotherapeutic drugs in cancer therapy and as nano-fillers to develop novel scaffolds for tissue engineering in regenerative medicine are evaluated. Via electrostatic and hydrophobic interactions, pH-responsive nanoconjugates are formed between the INPs and the doxorubicin (DOX) with an entrapment ratio of 77.9±3.9%. While the INPs show minimal cytotoxicity, the formed INP-DOX conjugates exhibit substantially stronger cytotoxic activity than free DOX against multiple cancer cell lines, suggesting a synergistic effect is established upon conjugation. The anti-cancer effects of the INP-DOX conjugates are further evaluated via in vivo xenograft assays by subcutaneously implanting DOX resistant cell line, SW620/Ad-300, into nude mice. The tumor volumes in mice treated with the INP-DOX conjugates are significantly less than those of the mice treated with free DOX. In addition, the INPs are further exploited as nano-fillers to develop fibrous scaffolds with collagen, via mimicking the porous matrix where the INPs are embedded under natural condition. Enhanced adhesion of smooth muscle cells (SMCs) and accelerated proliferation of mouse aortic SMCs are observed in this newly constructed scaffold. Overall, the results obtained from the present study suggest great potential of the INPs to be used as biocompatible nanomaterials in nanomedicine. The AGP-rich INP renders a glycoprotein architecture that is amenable for modification according to the functional designs, capable of being developed as versatile nanomaterials for extensive biomedical applications.

STATEMENT OF SIGNIFICANCE

Naturally occurring organic nanomaterials have drawn increasing interest for their potential biomedical applications in recent years. In this study, a new type of naturally occurring nanoparticles obtained from the sticky exudates on the adventitious roots of English ivy (H. helix), was explored for its potential biomedical application. In particular, the feasibilities of utilizing ivy nanoparticles (INPs) as nano-carriers for delivering chemotherapeutic drugs in cancer therapy and as nano-fillers to develop novel scaffolds for tissue engineering in regenerative medicine were evaluated both in vitro and in vivo. Overall, the results obtained from the present study suggest the great potential of the INPs to be used as biocompatible nanomaterials in nanomedicine. This study may open a totally new frontier for exploring the biomedical application of naturally occurring nanomaterials.

摘要

未标记

从常春藤(洋常春藤)粘性分泌物中获得的富含阿拉伯半乳聚糖蛋白(AGP)的纳米颗粒,因其出色的水溶性、低特性粘度、生物相容性和生物降解性,在纳米医学中显示出有前景的应用潜力。在本研究中,评估了利用常春藤纳米颗粒(INPs)作为纳米载体在癌症治疗中递送化疗药物以及作为纳米填料在再生医学中开发用于组织工程的新型支架的可行性。通过静电和疏水相互作用,INPs与阿霉素(DOX)之间形成了pH响应性纳米缀合物,包封率为77.9±3.9%。虽然INPs显示出最小的细胞毒性,但形成的INP-DOX缀合物对多种癌细胞系表现出比游离DOX更强的细胞毒性活性,表明缀合后建立了协同效应。通过将DOX耐药细胞系SW620/Ad-300皮下植入裸鼠进行体内异种移植试验,进一步评估了INP-DOX缀合物的抗癌效果。用INP-DOX缀合物处理的小鼠肿瘤体积明显小于用游离DOX处理的小鼠。此外,通过模拟INPs在自然条件下嵌入的多孔基质,进一步将INPs用作纳米填料与胶原蛋白一起开发纤维支架。在这种新构建的支架中观察到平滑肌细胞(SMCs)的粘附增强和小鼠主动脉SMC的增殖加速。总体而言,本研究获得的结果表明INPs在纳米医学中作为生物相容性纳米材料具有巨大潜力。富含AGP的INP呈现出一种糖蛋白结构,可根据功能设计进行修饰,能够被开发为用于广泛生物医学应用的多功能纳米材料。

意义声明

近年来,天然存在的有机纳米材料因其潜在的生物医学应用而越来越受到关注。在本研究中,探索了一种从洋常春藤(H. helix)不定根上的粘性分泌物中获得的新型天然纳米颗粒的潜在生物医学应用。特别是,在体外和体内评估了利用常春藤纳米颗粒(INPs)作为纳米载体在癌症治疗中递送化疗药物以及作为纳米填料在再生医学中开发用于组织工程的新型支架的可行性。总体而言,本研究获得的结果表明INPs在纳米医学中作为生物相容性纳米材料具有巨大潜力。这项研究可能为探索天然存在的纳米材料的生物医学应用开辟一个全新的领域。

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