Smart surface coating of drug nanoparticles with cross-linkable polyethylene glycol for bio-responsive and highly efficient drug delivery

被引:40
作者
Wei, Weijia [1 ]
Zhang, Xiujuan [1 ]
Chen, Xianfeng [2 ]
Zhou, Mengjiao [1 ]
Xu, Ruirui [1 ]
Zhang, Xiaohong [1 ]
机构
[1] Soochow Univ, Funct Nano & Soft Mat Lab FUNSOM & Technol, Jiangsu Key Lab Carbon Based Funct Mat & Devices, Suzhou 215123, Jiangsu, Peoples R China
[2] Univ Bradford, Fac Life Sci, Sch Chem & Forens Sci, Bradford BD7 1DP, W Yorkshire, England
基金
中国国家自然科学基金;
关键词
CANCER-THERAPY; BLOCK-COPOLYMER; SELF-DELIVERY; DOXORUBICIN; MICELLES; CELLS; COMBINATION; NANODRUG; SYSTEMS; DEMAND;
D O I
10.1039/c5nr09167e
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability and minimal premature release of therapeutic molecules during circulation in the blood stream. To meet this requirement, herein, we develop GSH-responsive and crosslinkable amphiphilic polyethylene glycol (PEG) molecules to modify carrier-free drug NPs. These PEG molecules can be cross-linked on the surface of the NPs to endow them with greater stability and the cross-link is sensitive to intracellular environment for bio-responsive drug release. With this elegant design, our experimental results show that the liberation of DOX from DOX-cross-linked PEG NPs is dramatically slower than that from DOX-non-cross-linked PEG NPs, and the DOX release profile can be controlled by tuning the concentration of the reducing agent to break the cross-link between PEG molecules. More importantly, in vivo studies reveal that the DOX-cross-linked PEG NPs exhibit favorable blood circulation half-life (> 4 h) and intense accumulation in tumor areas, enabling effective anti-cancer therapy. We expect this work will provide a powerful strategy for stabilizing carrier-free nanomedicines and pave the way to their successful clinical applications in the future.
引用
收藏
页码:8118 / 8125
页数:8
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