Scalable and cleavable polysaccharide nanocarriers for the delivery of chemotherapy drugs

Publication date: Available online 20 March 2018
Source:Acta Biomaterialia
Author(s): 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 SignificanceWhile 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.

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