Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan 250012, PR China.
Department of cardiovascular medicine, Shandong Provincial Hospital, Jinan 250021, PR China.
J Control Release. 2021 Jul 10;335:1-20. doi: 10.1016/j.jconrel.2021.05.012. Epub 2021 May 12.
Multidrug resistance (MDR) of cancer is a persistent problem in chemotherapy. Scientists have considered the overexpressed efflux transporters responsible for MDR and chemotherapy failure. MDR extremely limits the therapeutic effect of chemotherapy in cancer treatment. Many strategies have been applied to solve this problem. Multifunctional nanoparticles may be one of the most promising approaches to reverse MDR of tumor. These nanoparticles can keep stability in the blood circulation and selectively accumulated in the tumor microenvironment (TME) either by passive or active targeting. The stimuli-sensitive or organelle-targeting nanoparticles can release the drug at the targeted-site without exposure to normal tissues. In order to better understand reversal of MDR, three main strategies are concluded in this review. First strategy is the synergistic effect of chemotherapeutic drugs and ABC transporter inhibitors. Through directly inhibiting overexpressed ABC transporters, chemotherapeutic drugs can enter into resistant cells without being efflux. Second strategy is based on nanoparticles circumventing over-expressed efflux transporters and directly targeting resistance-related organelles. Third approach is the combination of multiple therapy modes overcoming cancer resistance. At last, numerous researches demonstrated cancer stem-like cells (CSCs) had a deep relation with drug resistance. Here, we discuss two different drug delivery approaches of nanomedicine based on CSC therapy.
癌症的多药耐药性（MDR）是化疗中的一个持续存在的问题。科学家们认为，过度表达的外排转运蛋白是导致 MDR 和化疗失败的原因。MDR 极大地限制了化疗在癌症治疗中的治疗效果。许多策略已被应用于解决这一问题。多功能纳米粒子可能是逆转肿瘤 MDR 的最有前途的方法之一。这些纳米粒子可以通过被动或主动靶向在血液循环中保持稳定，并选择性地积聚在肿瘤微环境（TME）中。刺激敏感或细胞器靶向纳米粒子可以在不暴露于正常组织的情况下在靶向部位释放药物。为了更好地理解逆转 MDR，本文总结了三种主要策略。第一种策略是化疗药物与 ABC 转运蛋白抑制剂的协同作用。通过直接抑制过度表达的 ABC 转运蛋白，化疗药物可以在没有外排的情况下进入耐药细胞。第二种策略基于纳米粒子绕过过度表达的外排转运蛋白，并直接靶向耐药相关的细胞器。第三种方法是多种治疗模式的联合，以克服癌症耐药性。最后，大量研究表明，癌症干细胞样细胞（CSC）与耐药性有很深的关系。在这里，我们讨论了两种基于 CSC 治疗的纳米医学的不同药物输送方法。
