Time-staggered delivery of erlotinib and doxorubicin by gold nanocages with two smart polymers for reprogrammable release and synergistic with photothermal therapy
Time-staggered delivery of erlotinib and doxorubicin by gold nanocages with two smart polymers for reprogrammable release and synergistic with photothermal therapy
复制标题
通过金纳米笼与两种智能聚合物交错时间递送厄洛替尼和阿霉素，可重新编程释放并与光热疗法协同作用
DOI：
10.1016/j.biomaterials.2019.119327
复制
发表时间：
2019-10-01
期刊：
影响因子：
14
通讯作者：
Zhang, Haiyuan
中科院分区：
文献类型：
--
作者：
Feng, Yanlin;Cheng, Yan;Zhang, Haiyuan
目前，光化学疗法是一种有效的抗癌疗法。最近有报道称，经表皮生长因子受体(EGFR)抑制剂厄洛替尼(Erlotinib，Erl)处理的癌细胞能显著协同DNA损伤剂阿霉素(Dox)诱导其凋亡。因此，我们设计了两个金纳米笼(Au NCS)微容器，分别覆盖了含有Er1和Dox的不同智能聚合物壳-PAA(pH响应型)和p(NIPAM-co-AM)(温度响应型)。酸性肿瘤微环境和近红外光照射可选择性激活Er1和Dox的释放。ER1和Dox的时间交错释放和光热治疗增强了凋亡信号通路，导致MCF-7(低EGFR表达)和A431(非常高EGFR表达)肿瘤细胞的杀伤率都有所提高，但后者的杀伤率更高。这种光化学策略在时间和空间上精确地控制药物暴露的顺序和持续时间，显著提高了对高表达EGFR的肿瘤的治疗效果。
Photochemotherapy is currently an effective anticancer therapy. Recently, it has been reported that cancer cells pretreated with epidermal growth factor receptor (EGFR) inhibitor erlotinib (Erl) can significantly synergize its apoptosis against the DNA damaging agent doxorubicin (Dox). As a result, we designed two gold nanocages (Au NCs) microcontainers covered with different smart polymer shell-PAA (pH responsive) and p (NIPAM-co-AM) (temperature responsive) containing Erl and Dox respectively. The acidic tumor microenvironment and NIR light irradiation can selectively activate the release of Erl and Dox. Time staggered release of Erl and Dox and photothermal therapy enhance the apoptotic signaling pathways, resulting in improved tumor cell killing in both MCF-7 (low EGFR expression) and A431 (very high EGFR expression) tumor cells, but more efficient in the latter. The photochemotherapy strategy controls the order and duration of drug exposure precisely in spatial and temporal, and significantly improves the therapeutic efficacy against high EGFR expressed tumors.