Carrier-free nanodrug-based virus-surface-mimicking nanosystems for efficient drug/gene co-delivery
Carrier-free nanodrug-based virus-surface-mimicking nanosystems for efficient drug/gene co-delivery
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基于无载体纳米药物的病毒表面模拟纳米系统，用于有效的药物/基因共同递送
DOI：
10.1039/c8bm01033a
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发表时间：
2018
影响因子：
6.6
通讯作者：
Liu Wenguang
中科院分区：
文献类型：
--
作者：
Sun Xuetan;Li Minghui;Yang Yang;Jia Huizhen;Liu Wenguang
自然启发的纳米粒子，从病原体到哺乳动物细胞，已经吸引了越来越多的关注，因为它们的特定功能和无与伦比的特性，通常需要在设计药物/基因递送非病毒载体。然而，非病毒载体的应用仍然受到低载药效率和/或低基因转染效率的限制。本文设计了一种新型的无载体纳米药物的病毒表面模拟基因递送纳米系统，其通过静电力将阿霉素纳米颗粒（DNP）凝聚到PEI/DNA纳米复合物的表面上，这将延长PEI/DNA的血液循环时间并赋予PEI/DNA纳米系统高载药特性。同时，表面粗糙度的增加也可以提高DNA的基因转染效率。体外和体内结果表明，具有高载药效率（97.5%）以及粗糙表面的无载体纳米药物基基因递送纳米系统可以增强纳米颗粒的内吞作用，从而增强癌症的化疗/基因联合治疗。这是首次使用软材料来设计模拟病毒表面的纳米载体，避免了无机材料因其不可降解性而产生的副作用。重要的是，我们精致的设计为开发用于癌症协同治疗的自然启发纳米颗粒开辟了新途径。
Nature-inspired nanoparticles, from pathogens to mammalian cells, have attracted increasing attention, for their specific functions and unparalled features that are often desired in designing drug/gene delivery nonviral vectors. However, the applications of nonviral vectors are still suffering from the limits of low drug loading efficiency and/or low gene transfection efficiency. Herein, a novel carrier-free nanodrug-based virus-surface-mimicking gene delivery nanosystem is designed by condensing doxorubicin nanoparticles (DNPs) onto the surface of the PEI/DNA nanocomplex through electrostatic force, which would prolong the blood circulation time of PEI/DNA and confer high drug loading characteristics to the PEI/DNA nanosystem. Meanwhile, the gene transfection efficiency of DNA can also be enhanced for the increased roughness of coated DNPs. The in vitro and in vivo results demonstrate that carrier-free nanodrug-based gene delivery nanosystems with high drug loading efficiency (97.5%) as well as a rough surface can enhance the endocytosis of the nanoparticles, and consequently enhance the chemo/gene co-therapy of cancers. This is the first time soft materials are used to design virus-surface-mimicking nanocarriers, avoiding the side effects of inorganic materials caused by their non-degradable property. Importantly, our delicate design opens a new pathway to develop nature-inspired nanoparticles for cancer synergistic therapy.