Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P.R. China; School of Pharmaceutical Sciences, Sun Yat-sen University, University Town, Guangzhou 510006, P.R. China.
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, P.R. China.
Crit Rev Ther Drug Carrier Syst. 2020;37(5):473-509. doi: 10.1615/CritRevTherDrugCarrierSyst.2020025052.
Multidrug resistance (MDR) remains a major obstacle to ensure effective chemotherapy in cancer patients. Several factors could be associated with cancer cells' drug resistance such as overexpression of P-glycoprotein (P-gp), cancer stem cells (CSCs), defect in apoptosis, mutation and alteration in DNA repair pathways, angiogenesis, autophagy, and modulation in metabolic enzymes. Until now, drug efflux by ABC transporters has been a univocal and well-established mechanism of chemotherapeutic associated drug resistance. To explore the mechanics involved in ABC transporter associated drug resistance, many crucial studies have been conducted from identification of drug binding sites to elucidation of their structure. Due to our continuous battle with drug resistance, several strategies have been employed to combat MDR, including P-gp modulators, siRNAs, antibodies, as well as peptides. Furthermore, various nanoparticle and different effective combination nanomedicine strategies also suggest some exciting results. Thus, to improve nanomedicine approaches to overcome MDR, in this evolutionary review, we have focused on fundamentals of possible strategies as well as the latest accomplishments to reverse MDR.
多药耐药（MDR）仍然是确保癌症患者有效化疗的主要障碍。许多因素可能与癌细胞的耐药性有关，如 P-糖蛋白（P-gp）的过度表达、癌症干细胞（CSC）、细胞凋亡缺陷、基因突变和 DNA 修复途径改变、血管生成、自噬以及代谢酶的调节。到目前为止，ABC 转运蛋白的药物外排已成为化疗相关药物耐药性的一种明确且成熟的机制。为了探索 ABC 转运蛋白相关药物耐药性的机制，已经进行了许多重要的研究，从药物结合部位的鉴定到结构的阐明。由于我们一直在与耐药性作斗争，因此已经采用了几种策略来对抗 MDR，包括 P-gp 调节剂、siRNA、抗体和肽。此外，各种纳米颗粒和不同有效的组合纳米医学策略也显示出一些令人兴奋的结果。因此，为了改进克服 MDR 的纳米医学方法，在本次进化综述中，我们重点关注了可能策略的基础以及逆转 MDR 的最新进展。
