用于药物传递系统的表面可调节聚合物纳米水凝胶的多功能官能化。

Versatile functionalization of surface-tailorable polymer nanohydrogels for drug delivery systems.

机构信息

Key Laboratory for Organic Electronics and Information Displays (KLOEID) & Jiangsu Key Laboratory for Biosensor, Institute of Advanced Materials (IAM), Jiangsu National Synergistic Innovation Center for Advanced Materials (SICAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing, 210023, China.

出版信息

Biomater Sci. 2018 Dec 18;7(1):247-261. doi: 10.1039/c8bm01093e.

Abstract

Surface decoration of nanohydrogels with functional molecules as well as nanomaterials offers a facile approach for developing multifunctional drug nanocarriers. Herein, the surface-tailorable polymer nanohydrogels, with the catechol groups as a universal anchor, were prepared by simple reflux-precipitation polymerization for versatile functionalization as drug delivery systems. The resultant polymer nanohydrogels were not only capable of delivering doxorubicin (DOX) through electrostatic interactions, but also exhibited facile conjugation with magnetic Fe3O4 nanoparticles and anticancer drug bortezomib (BTZ) via the versatile catechol-based coupling chemistry. The DOX and Fe3O4 loaded nanohydrogels (DOX-Fe3O4@NG) exhibited high DOX loading capability and triggered drug release behaviors in the acidic and redox environment. Furthermore, the DOX-Fe3O4@NG achieved improved cellular uptake in the presence of external magnetic field due to the active magnetic targeting properties. As for the dual drug delivery system (DOX-BTZ@NG), the DOX-BTZ@NG also released the drugs in response to the external stimuli including low pH and GSH presence, indicating their intelligent drug delivery properties. In particular, the DOX-BTZ@NG showed higher antiproliferation efficacy to cancer cells in comparison with the single drug loaded nanohydrogels, suggesting a synergistic effect of the dual drug combination therapy. The degradable poly(AA-co-DMA) nanohydrogels with surface-tailorable functionalities are thus a promising versatile platform for conjugation with both nanomaterials and drug molecules.

摘要

通过将功能分子和纳米材料表面修饰在纳米水凝胶上,为开发多功能药物纳米载体提供了一种简便的方法。本文通过简单的回流沉淀聚合制备了具有儿茶酚基团作为通用锚点的表面可修饰聚合物纳米水凝胶,作为多功能药物传递系统进行多功能化。所得聚合物纳米水凝胶不仅能够通过静电相互作用递送阿霉素(DOX),而且还能够通过通用的儿茶酚基偶联化学简便地与磁性 Fe3O4 纳米粒子和抗癌药物硼替佐米(BTZ)结合。载有 DOX 和 Fe3O4 的纳米水凝胶(DOX-Fe3O4@NG)表现出高 DOX 负载能力,并在酸性和氧化还原环境中表现出触发药物释放的行为。此外,由于具有主动磁靶向特性,在存在外部磁场的情况下,DOX-Fe3O4@NG 实现了更好的细胞摄取。对于双药物递送系统(DOX-BTZ@NG),DOX-BTZ@NG 也能够响应包括低 pH 和 GSH 存在的外部刺激释放药物,表明其具有智能药物递送特性。特别是,与单药载纳米水凝胶相比,DOX-BTZ@NG 对癌细胞表现出更高的增殖抑制作用,表明双重药物组合疗法具有协同作用。因此,具有表面可修饰功能的可降解聚(AA-co-DMA)纳米水凝胶是一种很有前途的多功能平台,可与纳米材料和药物分子结合。

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