Chem ( IF 19.1 ) Pub Date : 2020-07-10 , DOI: 10.1016/j.chempr.2020.06.013 Qunqun Bao , Ping Hu , Weiwei Ren , Yuedong Guo , Jianlin Shi
Surgery and subsequent chemotherapy are still the most adopted clinical modalities for bladder cancer treatments with the inevitable operation risks, chemotherapy toxicity, and high recurrence rate. Here, we report an unprecedented tumor cell dissociation strategy for malignant bladder tumor removal without the needs of conventional surgery and chemotherapy. A common metal ion chelator, ethylene diamine tetraacetic acid (EDTA), has been loaded into the interlayers of neurotensin (NT)-modified Zn-Al layered double hydroxide (LDH). Under the targeting by NT, such a nano-platform shows high affinity to bladder tumor cells, leading to the highly selective and efficient accumulation at the bladder tumor site. The released EDTA molecules deprive Ca2+ from the intercellular calcium-dependent connexin by EDTA-Ca2+ chelation, resulting in the tumor disaggregation that is then safely excreted out of body rather than killed using toxic chemodrugs, thus, ensuring excellent biosafety and extraordinarily high effectiveness.
中文翻译:
肿瘤细胞解离可去除恶性膀胱肿瘤
手术和随后的化学疗法仍然是膀胱癌治疗最常用的临床方法,具有不可避免的手术风险,化学疗法毒性和高复发率。在这里,我们报道了前所未有的肿瘤细胞解离策略,无需常规手术和化学疗法即可清除恶性膀胱肿瘤。常见的金属离子螯合剂乙二胺四乙酸(EDTA)已加载到神经降压素(NT)改性的Zn-Al层状双氢氧化物(LDH)的中间层中。在NT的靶向下,这样的纳米平台显示出对膀胱肿瘤细胞的高亲和力,从而导致在膀胱肿瘤部位的高度选择性和有效的积累。释放的EDTA分子通过EDTA-Ca从细胞间钙依赖性连接蛋白中剥夺了Ca 2+2+螯合,导致肿瘤分解,然后将其安全地排出体外,而不是使用有毒的化学药物杀死,从而确保了出色的生物安全性和极高的有效性。