State Key Laboratory of Reliability and Intelligence of Electrical Equipment, Hebei University of Technology, Tianjin 300130, China; Key Laboratory of Electromagnetic Field and Electrical Apparatus Reliability of Hebei Province, Hebei University of Technology, Tianjin 300130, China; Key Laboratory of Molecular Biophysics, Hebei Province, Institute of Biophysics, School of Sciences, Hebei University of Technology, Tianjin 300401, China.
Key Laboratory of Molecular Biophysics, Hebei Province, Institute of Biophysics, School of Sciences, Hebei University of Technology, Tianjin 300401, China.
Biochem Pharmacol. 2020 Aug;178:114062. doi: 10.1016/j.bcp.2020.114062. Epub 2020 May 31.
To overcome the adverse effects of conventional chemotherapy for cancers, various nanoparticles based drug delivery systems have been developed. However, nanoparticles delivering drugs directly to kill tumor cells still faced with challenges, because tumors possessed adopt complex mechanism to resist damages, which compromised the therapeutic efficacy. TMEM16A/CaCCs (Calcium activates chloride channels) has been identified to be overexpressed in lung adenocarcinoma which can serve as a novel tumor specific drug target in our previous work. Here, we developed a novel dual-targeted antitumor strategy via designing a novel nano-assembled, pH-sensitive drug-delivery system loading with specific inhibitors of TMEM16A against lung adenocarcinoma. For validation, we assayed the novel dual-targeting therapy on xenograft mouse model which exhibited significant antitumor activity and not affect mouse body weight. The dual targeting therapy accomplished in this study will shed light on the development of advanced antitumor strategy.
为了克服癌症常规化疗的不利影响，已经开发了各种基于纳米粒子的药物传递系统。然而，直接将药物递送到肿瘤细胞以杀死肿瘤细胞的纳米粒子仍面临挑战，因为肿瘤具有复杂的机制来抵抗损伤，从而降低了治疗效果。TMEM16A/CaCCs（钙激活氯离子通道）在肺腺癌中过度表达，在我们之前的工作中可以作为一种新的肿瘤特异性药物靶点。在这里，我们通过设计一种新型的纳米组装、pH 敏感的药物传递系统，装载针对肺腺癌的 TMEM16A 的特异性抑制剂，开发了一种新的双靶向抗肿瘤策略。为了验证，我们在异种移植小鼠模型上进行了新型双靶向治疗的实验，结果显示该治疗具有显著的抗肿瘤活性，且不影响小鼠体重。本研究中的双靶向治疗为先进抗肿瘤策略的发展提供了思路。
