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Scalable and cleavable polysaccharide nanocarriers for the delivery of chemotherapy drugs
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2018-03-20 , DOI: 10.1016/j.actbio.2018.03.024
Hao Wang , Tingting Dai , Shengli Li , Shuyan Zhou , Xiaojing Yuan , Jiayi You , Chenglong Wang , Vincent Mukwaya , Guangdong Zhou , Guojun Liu , Xiaohui Wei , Hongjing Dou

While polysaccharide-based nanocarriers have been recognized for their crucial roles in tumor theranostics, the industrial-scale production of nanotherapeutics still remains a significant challenge. Most current approaches adopt a postpolymerization self-assembly strategy that follows a separate synthetic step and thus suffers from subgram scale yields and a limited range of application. In this study, we demonstrate the kilogram-scale formation of polysaccharide–polyacrylate nanocarriers at concentrations of up to 5 wt% through a one-pot approach – starting from various acrylate monomers and polysaccharides – that combines aspects of hydrophobicity-induced self-assembly with the free radical graft copolymerization of acrylate monomers from polysaccharide backbones into a single process that is thus denoted as a graft copolymerization induced self-assembly. We also demonstrate that this novel approach is applicable to a broad range of polysaccharides and acrylates. Notably, by choosing a crosslinker that bears a disulfide group and two vinyl capping groups to structurally lock the nanocarriers, the products are rendered cleavable in the reducing environments encountered at tumor sites and thus provide ideal candidates for the construction of anticancer nanotherapeutic systems. In vitro and in vivo studies demonstrated that the use of this nanocarrier for the delivery of doxorubicin hydrochloride (DOX) significantly decreased the side effects of DOX and improved the bio-safety of the chemotherapy accordingly.

Statement of Significance

While polysaccharide-based nanocarriers have been recognized for their crucial roles in tumor theranostics, the industrial-scale production of these nanotherapeutics still remains a significant challenge. Most current approaches adopt a post-polymerization self-assembly strategy which that follows a separate synthetic step, and thus suffers from sub-gram scale yields and a limited range of application. HereIn this study, the hydrophobic effect was combined with free radical polymerization to facilitate the graft copolymerization- induced self-assembly (GISA) of acrylate monomers with various hydrophobicities to construct cleavable polysaccharide-–polyacrylate nanocarriers-suitcases at a high efficiency with excellent potential for industrial-scale production. wWe envision that these nanocarriers-suitcases will contribute to the development of tumor nanotheranostics that combine the biological functionalities of polysaccharides with the unmatched application-specific flexibility of nanocarriers.



中文翻译:

可扩展和可裂解的多糖纳米载体,用于化疗药物的输送

尽管基于多糖的纳米载体在肿瘤治疗学中的关键作用已得到公认,但纳米治疗剂的工业规模生产仍然是一个重大挑战。当前大多数方法采用聚合后的自组装策略,该策略遵循单独的合成步骤,因此存在亚克级规模的收率和有限的应用范围。在这项研究中,我们通过一锅法(从各种丙烯酸酯单体和多糖开始)结合了疏水性诱导的自组装和自由基接枝的方法,证明了高达5 wt%浓度的多糖-聚丙烯酸酯纳米载体的公斤级形成从多糖主链上丙烯酸酯单体的共聚合成一个单一的过程,因此被称为接枝共聚诱导的自组装。我们还证明了这种新颖的方法适用于多种多糖和丙烯酸酯。值得注意的是,通过选择带有二硫键和两个乙烯基封端基团的交联剂来结构上锁定纳米载体,体外体内研究表明,使用这种纳米载体递送盐酸阿霉素(DOX)可以显着降低DOX的副作用,并相应提高化疗的生物安全性。

重要声明

尽管基于多糖的纳米载体在肿瘤治疗学中的关键作用已得到公认,但这些纳米治疗剂的工业规模生产仍然是一项重大挑战。当前大多数方法采用聚合后的自组装策略,该策略遵循单独的合成步骤,因此存在亚克级规模的收率和有限的应用范围。在此,本研究将疏水作用与自由基聚合结合起来,以促进具有各种疏水性的丙烯酸酯单体的接枝共聚诱导自组装(GISA),从而以高效率和极好的潜力构建可裂解的多糖-聚丙烯酸酯纳米载体-手提箱。工业规模生产。

更新日期:2018-03-20
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