Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, China.
Adv Drug Deliv Rev. 2017 Jun 1;115:46-56. doi: 10.1016/j.addr.2017.04.006. Epub 2017 Apr 20.
Efficacy of regular chemotherapy is significantly hampered by multidrug resistance (MDR) and severe systemic toxicity. The reduced toxicity has been evidenced after administration of drug liposomes, consisting of the first generation of regular drug liposomes, the second generation of long-circulation drug liposomes, and the third generation of targeting drug liposomes. However, MDR of cancers remains as an unsolved issue. The objective of this article is to review the dual-functional drug liposomes, which demonstrate the potential in overcoming MDR. Herein, dual-functional drug liposomes are referring to the drug-containing phospholipid bilayer vesicles that possess a dual-function of providing the basic efficacy of drug and the extended effect of the drug carrier. They exhibit unique roles in treatment of resistant cancer via circumventing drug efflux caused by adenosine triphosphate binding cassette (ABC) transporters, eliminating cancer stem cells, destroying mitochondria, initiating apoptosis, regulating autophagy, destroying supply channels, utilizing microenvironment, and silencing genes of the resistant cancer. As the prospect of an estimation, dual-functional drug liposomes would exhibit more strength in their extended function, hence deserving further investigation for clinical validation.
常规化疗的疗效受到多药耐药(MDR)和严重的全身毒性的显著阻碍。在给予药物脂质体后,毒性已经降低,这些脂质体包括第一代常规药物脂质体、第二代长循环药物脂质体和第三代靶向药物脂质体。然而,癌症的 MDR 仍然是一个未解决的问题。本文的目的是综述双功能药物脂质体,该脂质体显示出克服 MDR 的潜力。在这里,双功能药物脂质体是指含有药物的磷脂双层囊泡,具有提供药物基本疗效和药物载体扩展效应的双重功能。它们通过绕过三磷酸腺苷结合盒(ABC)转运蛋白引起的药物外排、消除癌症干细胞、破坏线粒体、引发细胞凋亡、调节自噬、破坏供应渠道、利用微环境以及沉默耐药性癌症的基因,在治疗耐药性癌症方面发挥独特作用。作为一个估计的前景,双功能药物脂质体在其扩展功能方面将表现出更强的作用,因此值得进一步研究以进行临床验证。