Ganoth Assaf, Merimi Keren Cohen, Peer Dan
The Interdisciplinary Center (IDC) , P.O. Box 167, Herzliya 46150 , Israel.
Expert Opin Drug Deliv. 2015 Feb;12(2):223-38. doi: 10.1517/17425247.2015.960920. Epub 2014 Sep 16.
Cancer remains the leading cause of death worldwide. Numerous therapeutic strategies that include smart biological treatments toward specific cellular pathways are being developed. Yet, inherent and acquired multidrug resistance (MDR) to chemotherapeutic drugs remains the major obstacle in effective cancer treatments.
Herein, we focused on an implementation of nanoscale drug delivery strategies (nanomedicines) to treat tumors that resist MDR. Specifically, we briefly discuss the MDR phenomenon and provide structural and functional characterization of key proteins that account for MDR. We next describe the strategies to target tumors using nanoparticles and provide a mechanistic overview of how changes in the influx:efflux ratio result in overcoming MDR.
Various strategies have been applied in preclinical and clinical settings to overcome cancer MDR. Among them are the use of chemosensitizers that aim to sensitize the cancer cells to chemotherapeutic treatment and the use of nanomedicines as delivery vehicles that can increase the influx of drugs into cancer cells. These strategies can enhance the therapeutic response in resistant tumors by bypassing efflux pumps or by increasing the nominal amounts of therapeutic payloads into the cancer cells at a given time point.
癌症仍然是全球主要的死亡原因。目前正在开发许多治疗策略，包括针对特定细胞途径的智能生物治疗方法。然而，对化疗药物的固有和获得性多药耐药性（MDR）仍然是有效治疗癌症的主要障碍。
在此，我们重点关注纳米级药物递送策略（纳米药物）在治疗耐多药肿瘤中的应用。具体而言，我们简要讨论了多药耐药现象，并对导致多药耐药的关键蛋白进行了结构和功能表征。接下来，我们描述了使用纳米颗粒靶向肿瘤的策略，并提供了关于流入：流出比率变化如何导致克服多药耐药的机制概述。
在临床前和临床环境中已经应用了各种策略来克服癌症多药耐药。其中包括使用化学增敏剂以使癌细胞对化疗治疗敏感，以及使用纳米药物作为递送载体，其可以增加药物进入癌细胞的量。这些策略可以通过绕过外排泵或在给定时间点增加进入癌细胞的治疗有效载荷的标称量来增强对耐药肿瘤的治疗反应。
