For enhanced intracellular drug release in leukemia, the structure of 6-thioguanine (6-TG) based pH/reduction responsive polymeric prodrug nanoparticles was constructed by conjugating 6-TG to dialdehyde sodium alginate (DSA) via acid-labile Schiff base linkage followed by the ultrasound-assisted oxidation of thiol groups to disulfide cross-links. The nanoparticles are stable at pH 7.4 containing 0 and 10 μM glutathione (GSH) with almost no drug release, but a cumulative drug release rate of up to 98.6% in 228 h was observed at pH 5.0 with 20 mM GSH and the cumulative drug release in the first 48 hours was over three times as much as that in the case of 10 mM GSH, indicating that GSH and pH dual-stimulation can significantly elevate tumour cell-selective drug release. In comparison with free 6-TG, this system exhibited a slightly higher inhibition ratio on HL-60 cancer cells, while an obviously reduced cytotoxicity was observed for healthy liver cell line L-O2. Furthermore, in vitro cell studies further confirmed the efficient cellular uptake of the system and enhanced intracellular drug release in the HL-60 cells.

中文翻译：

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基于6-硫鸟嘌呤-二醛海藻酸钠缀合物的pH和还原活化的聚合物前药纳米颗粒，可增强白血病中细胞内药物的释放†

为了增强细胞内的药物释放在白血病，6-硫鸟嘌呤（6-TG）的基础的pH /还原反应的聚合物前药纳米颗粒的结构，通过缀合6-TG到藻酸钠二醛（DSA）构造通过酸不稳定的席夫（Schiff）碱键，然后通过超声辅助将硫醇基氧化为二硫键。纳米颗粒在含有0和10μM谷胱甘肽（GSH）的pH 7.4时稳定，几乎没有药物释放，但是在pH 5.0和20 mM GSH的情况下，在228小时内累积药物释放率高达98.6％，并且累积药物释放在最初的48小时中，GSH的作用是10 mM GSH的三倍以上，这表明GSH和pH的双重刺激可以显着提高肿瘤细胞选择性药物的释放。与游离6-TG相比，该系统对HL-60癌细胞的抑制率略高，而健康肝细胞L-O2的细胞毒性明显降低。此外，体外 细胞研究进一步证实了该系统对细胞的有效吸收，并在HL-60细胞中增强了细胞内药物的释放。