Department of Pharmaceutical analysis, School of Pharmacy, and The State Key Laboratory of Cancer Biology (CBSKL), The Fourth Military Medical University, 169th Changle West Road, Xi'an, Shaanxi, 710032, China.
Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
J Exp Clin Cancer Res. 2017 Sep 6;36(1):119. doi: 10.1186/s13046-017-0586-1.
Previous clinical trials have already demonstrated that combinations of two or more drugs were more effective in the cancer treatment, especially sequential photodynamic design combing with sequential chemotherapy. In our study, we propose a ternary cocktail NP delivery system based on self-decomposable NPs, which could realize synergistic chemo-photodynamic therapy through double loading chemo-drugs and multi-level programmable PDT treatment.
PS drug methylene blue (MB) was encapsulated into the center of the NP, NP, and NP carriers through "grown-in" loading mechanism, which was released based on the drug concentration difference of the drug release environment. NP, NP, and NP carriers have three different drug release profiles, which could realize multi-level programmable PDT treatment. At the same time, antitumor drug gemcitabine hydrochloride (GM) and Docetaxel (DTX), were chosen as the double loading chemo-drugs that absorbed onto the NP and NP surface, respectively. In specific, various particle configurations were used for modulating the inner MB sequential release with three pulse T. Also, by adjusting the NP and NP configuration, the release interval lag time between absorbed GM and DTX can be successfully modulated to achieve maximized chemotherapeutic efficacy.
In vitro and in vivo results demonstrated that these three pulses T and the sustained release of MB could maximize the multi-level programmable PDT treatment. And the absorbed GM and DTX also have a release time lag of 12 h, which has been proved as the most effectiveness synergistic interval lag time in the cancer treatment.
Such a precise sequential release manner ternary cocktail NPs provided a promising platform for efficient and safe chemo-photodynamic therapy, which serves as a promising drug delivery system to cure cancer in the future.
先前的临床试验已经证明，两种或多种药物的联合使用在癌症治疗中更为有效，特别是光动力疗法与化学疗法的序贯设计。在我们的研究中，我们提出了一种基于自分解纳米颗粒的三元鸡尾酒 NP 递药系统，该系统可以通过双重负载化疗药物和多级程控 PDT 治疗来实现协同化疗-光动力治疗。
PS 药物亚甲蓝（MB）通过“生长”加载机制被包裹到 NP 的中心，NP 和 NP 载体通过药物释放环境的药物浓度差异进行释放。NP、NP 和 NP 载体具有三种不同的药物释放曲线，可以实现多级程控 PDT 治疗。同时，选择盐酸吉西他滨（GM）和多西他赛（DTX）作为双重负载化疗药物，分别吸附到 NP 和 NP 表面。具体来说，各种粒子结构用于调节内源性 MB 的顺序释放，采用三个脉冲 T。此外，通过调整 NP 和 NP 的结构，可以成功调节吸收的 GM 和 DTX 之间的释放间隔滞后时间，以实现最大化的化疗效果。
体外和体内结果表明，这三个脉冲 T 和 MB 的持续释放可以最大限度地提高多级程控 PDT 治疗效果。并且吸收的 GM 和 DTX 也有 12 小时的释放时间滞后，这已被证明是癌症治疗中最有效的协同滞后时间。
这种精确的顺序释放方式三元鸡尾酒 NPs 为高效和安全的化疗-光动力治疗提供了一个有前途的平台，有望成为未来治疗癌症的药物输送系统。
