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基于纤维素纳米晶体的生物相容性和 pH 响应性纳米水凝胶用于增强毒性活性氧的生成。

A biocompatible and pH-responsive nanohydrogel based on cellulose nanocrystal for enhanced toxic reactive oxygen species generation.

机构信息

Jiangsu Key Lab for the Chemistry and Utilization of Agro-Forest Biomass, Jiangsu Co-Innovation Centre for Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Longpan Road 159, Nanjing 210037, China.

Jiangsu Key Lab for the Chemistry and Utilization of Agro-Forest Biomass, Jiangsu Co-Innovation Centre for Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Longpan Road 159, Nanjing 210037, China.

出版信息

Carbohydr Polym. 2021 Apr 15;258:117685. doi: 10.1016/j.carbpol.2021.117685. Epub 2021 Jan 24.

DOI:10.1016/j.carbpol.2021.117685
PMID:33593558
Abstract

Traditional therapeutic regimens are currently far from satisfactory, and the integration of biocompatible carbohydrate polymers and nanotechnologies with conventional therapeutics has become a focus of research in cancer therapy. Herein, A novel biocompatible and pH-responsive nanohydrogel composed of two functional polymeric chains was developed from cellulose nanocrystals (CNCs) and 5-aminolevulinic acid (ALA), or dopamine (DPA). The biological molecules PDA and ALA were respectively conjugated to CNC through the coordination of iron ions to form two functional polymeric chains (PDA/Fe@CNC and ALA/Fe@CNC). The PDA/Fe@CNC chain increased the adhesion of the nanohydrogels to cells, while the ALA/Fe@CNC chain significantly increased reactive oxygen species (ROS) production. Furthermore, PTX molecules loaded into the nanohydrogels combined with ROS to efficiently kill tumor cells. The nanohydrogels displayed excellent cell affinity, high ROS yield (8.0-fold greater than that in control), and strong cytotoxicity (2.7 % of cell viability). The present study highlights the great potential of biocompatible natural polysaccharide-based materials for biomedical applications, and provides a new strategy for reducing the toxicity and side effects associated with traditional chemotherapy, demonstrating a novel antitumor treatment paradigm with high-efficiency but with only minor side effects.

摘要

传统的治疗方案目前远不能令人满意,将生物相容性碳水化合物聚合物和纳米技术与传统疗法相结合已成为癌症治疗研究的焦点。本文中,通过铁离子的配位作用,将生物分子 PDA 和 ALA 分别接枝到纳米纤维素晶体(CNC)上,形成了两种功能性聚合物链(PDA/Fe@CNC 和 ALA/Fe@CNC),开发了一种由纤维素纳米晶体(CNC)和 5-氨基乙酰丙酸(ALA)或多巴胺(DPA)组成的新型生物相容性和 pH 响应性纳米水凝胶。PDA/Fe@CNC 链增加了纳米水凝胶对细胞的黏附性,而 ALA/Fe@CNC 链则显著增加了活性氧物质(ROS)的产生。此外,负载到纳米水凝胶中的 PTX 分子与 ROS 结合,有效地杀死了肿瘤细胞。该纳米水凝胶表现出优异的细胞亲和力、高 ROS 产率(比对照组高 8.0 倍)和强细胞毒性(细胞活力为 2.7%)。本研究突出了基于生物相容性天然多糖的材料在生物医学应用中的巨大潜力,为降低传统化疗相关毒性和副作用提供了新策略,展示了一种高效但副作用较小的新型抗肿瘤治疗范例。

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