Zwitterionic Polypeptide-Based Nanodrug Augments pH-Triggered Tumor Targeting via Prolonging Circulation Time and Accelerating Cellular Internalization
Zwitterionic Polypeptide-Based Nanodrug Augments pH-Triggered Tumor Targeting via Prolonging Circulation Time and Accelerating Cellular Internalization
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基于两性离子多肽的纳米药物通过延长循环时间和加速细胞内化增强 pH 触发的肿瘤靶向
DOI：
10.1021/acsami.0c11747
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发表时间：
2020-10-14
影响因子：
9.5
通讯作者：
Chen, Shengfu
中科院分区：
文献类型：
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作者：
Xue, Weili;Trital, Ashish;Chen, Shengfu
为了提高抗肿瘤疗效和减少化疗药物对健康器官的显著副作用，开发了一种基于两性离子聚（谷氨酸赖氨酸-半胱氨酸）肽支架的新型白蛋白模拟纳米药物，通过延长循环时间和加速细胞内化来增强pH触发的肿瘤靶向。结果显示，在肿瘤微环境pH 6.7下，MCF-7细胞对纳米药物的内化比Doxil快得多，甚至与游离阿霉素（Dox）相当，而RAW-264.7细胞对纳米药物的内化仅为Doxil的27.4 +/- 7.6%。此外，“隐形”纳米药物的显著延长的循环时间也与长循环Doxil相当。因此，在循环半衰期之前，纳米药物在肿瘤中的积累远高于在肝脏和肾脏中的积累，这与在该时间尺度内在肝脏和肾脏中积累的大多数其他纳米药物显著不同。治疗18天后，纳米药物的肿瘤抑制率远高于Doxil（93.2 +/- 3.0% vs 54.2 +/- 6.5%），而纳米药物治疗的小鼠的平均体重比Doxil高26.9 +/- 6.7%。这表明纳米药物的长循环时间和快速细胞内化的协同作用可以显著增强肿瘤靶向性。这种方法可能会使传统的化疗方法年轻化。
To augment the antitumor efficacy and minimize the significant side effects of chemotherapeutic drugs on health organs, a novel albumin-mimicking nanodrug, which is based on zwitterionic poly(glutamatyl lysine-co-cysteine) peptides scaffold, is developed to enhance pH-triggered tumor targeting via prolonging circulation time and accelerating cellular internalization. Results showed that the internalization of the nanodrug by MCF-7 cells is much faster than that by Doxil and even comparable to that by free doxorubicin (Dox) at tumor microenvironmental pH 6.7, whereas the internalization of the nanodrug is only 27.4 +/- 7.6% of the Doxil by RAW-264.7 cells. Moreover, the significantly prolonged circulation time of the "stealthy" nanodrug was also comparable to that of the long circulating Doxil. As a result, the accumulation of the nanodrug in the tumor is much higher than that in the liver and kidney before the circulation half-life, which is significantly different from most other nanodrugs accumulated in the liver and kidney in this time scale. The tumor inhibition rate of the nanodrug was much higher than that of Doxil (93.2 +/- 3.0% vs 54.2 +/- 6.5%) after 18 day treatment, while the average bodyweight of the mice treated by the nanodrug was 26.9 +/- 6.7% higher than that by Doxil. This indicated that the synergetic effect of long circulation time and fast cellular internalization of the nanodrug can significantly augment tumor targeting. This method might rejuvenate the traditional chemotherapeutic treatment.