前药
纳米医学
胶束
共轭体系
药物输送
姜黄素
体内
生物物理学
化学
生物化学
材料科学
核化学
纳米颗粒
纳米技术
有机化学
生物
水溶液
聚合物
生物技术
作者
Kaili Wang,Caixia Guo,Shaohua Zou,Yueming Yu,Xinxin Fan,Bingjie Wang,Mengna Liu,Lei Fang,Daquan Chen
标识
DOI:10.1080/21691401.2018.1466147
摘要
To remedy the problems resulting from the usage of anti-cancer drugs in cancer chemotherapy, such as deficient drug concentration in tumour cells, low water-solubility and non-specific distribution of antitumour drugs, a kind of reduction-sensitive polymer prodrug of curcumin (Cur) containing in the nano-echinus was synthesized and designed. The nano-echinus-like nanomedicine presented synergistic effect with glycyrrhetic acid (GA) and oligomeric hyaluronic (HA) for targeting and combating HepG2 human liver cancer cell. Firstly, a kind of small molecular prodrug of Cur, dithiodipropionic acid-Cur (-SS-Cur), was chemically conjugated onto the side chain of the conjugated glycyrrhetic acid- oligomeric hyaluronic (GA-HA) to generate an amphiphilic polymeric prodrug of Cur, GA-HA-SS-Cur. The obtained GA-HA-SS-Cur prodrug and subsidiary material mPEG-DSPE could self-assemble into a sea urchin-like micelles in aqueous media and release Cur rapidly in response to glutathion (GSH). Then, Cur was loaded into the nano-echinus with a particle size of (118.1 ± 0.2 nm) and drug-loading efficiency of (8.03 ± 2.1%). The structure of GA-HA-SS-Cur was characterized by 1H-NMR in this report. The morphology of micelles was observed with a transmission electron microscope (TEM). Subsequently, the reduction-sensitivity of the nano-echinus was confirmed by the changes in in-vitro drug release after different concentrations of GSH treatment. Besides, the cellular uptake behaviour and MTT assays of the nano-echinus were investigated, suggesting that the nano-echinus was of desirable safety and could be taken into HepG2 cells in a time-dependent manner. Later, anti-tumour efficacy in vivo revealed the effective inhibition of tumour growth.
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