Cano-Cortes Maria Victoria, Laz-Ruiz Jose Antonio, Diaz-Mochon Juan Jose, Sanchez-Martin Rosario Maria
GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Avda. Ilustración 114, 18016 Granada, Spain.
Department of Medicinal & Organic Chemistry, Excellence Research Unit of "Chemistry Applied to Biomedicine and the Environment", Faculty of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
Polymers (Basel). 2020 Jun 1;12(6):1265. doi: 10.3390/polym12061265.
Despite the large number of polymeric nanodelivery systems that have been recently developed, there is still room for improvement in terms of therapeutic efficiency. Most reported nanodevices for controlled release are based on drug encapsulation, which can lead to undesired drug leakage with a consequent reduction in efficacy and an increase in systemic toxicity. Herein, we present a strategy for covalent drug conjugation to the nanodevice to overcome this drawback. In particular, we characterize and evaluate an effective therapeutic polymeric PEGylated nanosystem for controlled pH-sensitive drug release on a breast cancer (MDA-MB-231) and two lung cancer (A549 and H520) cell lines. A significant reduction in the required drug dose to reach its half maximal inhibitory concentration (IC50 value) was achieved by conjugation of the drug to the nanoparticles, which leads to an improvement in the therapeutic index by increasing the efficiency. The genotoxic effect of this nanodevice in cancer cells was confirmed by nucleus histone H2AX specific immunostaining. In summary, we successfully characterized and validated a pH responsive therapeutic polymeric nanodevice in vitro for controlled anticancer drug release.
尽管最近已经开发出大量的聚合物纳米递送系统，但在治疗效率方面仍有改进的空间。大多数报道的用于控释的纳米器件是基于药物包封，这可能导致不期望的药物泄漏，从而降低疗效并增加全身毒性。在此，我们提出一种将药物共价连接到纳米器件上的策略，以克服这一缺点。特别是，我们表征并评估了一种有效的治疗性聚合物聚乙二醇化纳米系统，该系统在乳腺癌（MDA-MB-231）和两种肺癌（A549和H520）细胞系上实现对pH敏感的药物控释。通过将药物与纳米颗粒结合，达到其半数最大抑制浓度（IC50值）所需的药物剂量显著降低，这通过提高效率导致治疗指数的提高。通过细胞核组蛋白H2AX特异性免疫染色证实了该纳米器件在癌细胞中的遗传毒性作用。总之，我们成功地表征并验证了一种体外pH响应性治疗性聚合物纳米器件用于控释抗癌药物。
