Biological stimuli responsive drug carriers based on keratin for triggerable drug delivery
Biological stimuli responsive drug carriers based on keratin for triggerable drug delivery
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基于角蛋白的生物刺激响应药物载体，用于可触发的药物输送
DOI：
10.1039/c2jm34136k
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Huang, Yong
中科院分区：
文献类型：
--
作者：
Li, Qinmei;Zhu, Lijun;Huang, Yong
报道了一种新型的基于角蛋白接枝聚乙二醇共聚物的药物载体。通过硫醇-烯点击化学合成了不同接枝密度的角蛋白-g-PEG共聚物。利用接枝共聚物的两亲性和硫醇基团，在水溶液中制备以PEG链和角蛋白为核心稳定的纳米颗粒，其具有谷胱甘肽（GSH）可裂解的交联。角蛋白-g-PEG共聚物纳米粒可作为阿霉素盐酸盐（DOX中心点HCl）的优异载体，最高负载容量为18.1%（w/w）。负载的DOX的释放对GSH的浓度敏感，特别是在细胞水平的GSH浓度下。胰蛋白酶可以进一步触发纳米颗粒中负载的DOX的释放。体外细胞摄取实验表明，从DOX负载的角蛋白-g-PEG纳米颗粒释放的DOX可以有效地内化到细胞中，并且负载的DOX在较高GSH浓度下显示出更快地释放到细胞核中。该载体作为药物载体在肿瘤细胞内给药治疗中具有广阔的应用前景。
A novel drug carrier with dual triggerable release properties based on keratin graft poly(ethylene glycol) (keratin-g-PEG) copolymers is reported. Keratin-g-PEG copolymers with different graft densities are synthesized through thiol-ene click chemistry. Taking advantage of the amphiphilicity and the thiol groups of the graft copolymer, nanoparticles stabilized with PEG chains and keratin as the core, bearing glutathione (GSH) cleavable cross-links, are fabricated in aqueous solutions. The keratin-g-PEG copolymer nanoparticles can serve as excellent carriers for doxorubicin hydrochloride salt (DOX center dot HCl) with a highest loading capacity of 18.1% (w/w). The release of the loaded DOX is sensitive to the concentration of GSH, especially at a GSH concentration of cellular level. Trypsin can further trigger the release of the loaded DOX in the nanoparticles. In vitro cellular uptake experiments indicate that DOX released from the DOX-loaded keratin-g-PEG nanoparticles can be internalized into the cells efficiently, and the loaded DOX shows a faster release into the nuclei of the cells under higher GSH concentrations. The carriers have promising applications as drug carriers for intracellular drug delivery for cancer therapy.