Dual pH-responsive "charge-reversal like" gold nanoparticles to enhance tumor retention for chemo-radiotherapy
Dual pH-responsive "charge-reversal like" gold nanoparticles to enhance tumor retention for chemo-radiotherapy
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双 pH 响应“电荷反转样”金纳米粒子可增强放化疗的肿瘤保留
DOI：
10.1007/s12274-019-2518-1
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发表时间：
2019
期刊：
影响因子：
9.9
通讯作者：
Yuan Zhi
中科院分区：
文献类型：
--
作者：
Zhang Xiaolei;Zhang Chuangnian;Cheng Mingbo;Zhang Yahui;Wang Wei;Yuan Zhi
肿瘤微环境ph响应性聚集（pH-responsive aggregation in tumor micro-environment， TME）策略为增强肿瘤潴留和充分发挥治疗效果提供了一个有趣的平台。在本研究中，我们设计了一种用于联合放化疗的智能双ph响应自聚集纳米金系统（Au@PAH-Pt/DMMA），该系统利用“电荷逆转”策略实现顺铂前药在TME中的不可逆稳定聚集和ph特异性释放。响应性聚集使Au@PAH-Pt/DMMA的细胞摄取增加55%-60%，x射线照射后Pt的细胞摄取可进一步增加80%。此外，反应性聚集极大地减缓了肿瘤体内的外排速率。该系统不仅作为化疗药物促进B16细胞凋亡（30.4%），还通过促进细胞凋亡作为放射增敏剂（55.3%）增强放化疗（CRT）的效果。菌落形成实验结果与B16细胞存活曲线拟合，计算出增敏增强比（SER）为1.29，显示出良好的放射增敏能力。当x射线照射时，该纳米平台达到了理想的治疗效果，在给药频率和x射线剂量较低的情况下，Au@PAH-Pt/DMMA的肿瘤抑制率达到91.6%。综上所述，双ph响应纳米粒子Au@PAH-Pt/DMMA可有效提高放化疗联合治疗肿瘤的疗效，为癌症治疗的临床转化提供了一种潜在的方法。
The strategy of pH-responsive aggregation in tumor micro-environment (TME) provides an intriguing platform for enhancing tumor retention and exerting therapeutic effects sufficiently. In this work, we have designed an intelligent dual pH-responsive self-aggregating nano gold system (Au@PAH-Pt/DMMA) for the combined chemo-radiotherapy, in which a “charge-reversal like” strategy was utilized to realize irreversible stable aggregation and pH-specific release of cisplatin prodrug in TME. Responsive aggregation increases the cellular uptake of Au@PAH-Pt/DMMA by 55%–60%, and the cellular uptake of Pt after X-ray irradiation can be further enhanced by 80%. Additionally, responsive aggregation greatly slows down the rate of efflux from tumorin vivo. This system not only promotes B16 cell apoptosis as a chemotherapeutic agent (30.4%), it also enhances the effect of chemo-radiotheray (CRT) by promoting apoptosis as a radiosensitizer (55.3%). The colony formation assay results were fitted to cell survival curve of B16 cells and the sensitization enhancement ratio (SER) was calculated to be 1.29, which shows a good radiosensitizing ability. When exposed to X-ray, this nanoplatform reached the ideal therapeutic effect, and the tumor inhibition rate of Au@PAH-Pt/DMMA reached 91.6% with low drug administration frequency and dose of X-ray. Overall, the dual pH-responsive nanoparticles Au@PAH-Pt/DMMA could effectively enhance tumor therapeutic efficiency by combined chemo-radiotherapy, which provides a potential method for clinical transformation of cancer treatment.