Department of Biomedical Engineering, College of Engineering , Peking University , Beijing , 100871 , China.
School of Environment , Harbin Institute of Technology , Harbin 150080 , China.
Bioconjug Chem. 2018 Dec 19;29(12):3967-3981. doi: 10.1021/acs.bioconjchem.8b00692. Epub 2018 Nov 28.
Chemotherapy suffers from some limitations such as poor bioavailability, rapid clearance from blood, poor cellular uptake, low tumor accumulation, severe side effects on healthy tissues and most importantly multidrug resistance (MDR) in cancer cells. Nowadays, a series of smart drug delivery system (DDS) based on amphiphilic drug conjugates (ADCs) has been developed to solve these issues, including polymer-drug conjugate (PDC), phospholipid-mimicking prodrugs, peptide-drug conjugates (PepDCs), pure nanodrug (PND), amphiphilic drug-drug conjugate (ADDC), and Janus drug-drug conjugate (JDDC). These ADCs can self-assemble into nanoparticles (NPs) or microbubbles (MBs) for targeted drug delivery by minimizing the net amount of excipients, realizing great goals, such as stealth behavior and physical integrity, high drug loading content, no premature leakage, long blood circulation time, fixed drug combination, and controlled drug-release kinetics. Besides, these self-assembled systems can be further used to load additional therapeutic agents and imaging contrast agents for combined therapy, personalized monitoring of in vivo tumor targeting, and the pharmacokinetics of drugs for predicting the therapeutic outcome. In this review, we will summarize the latest progress in the development of ADCs based combination chemotherapy and discuss the important roles for overcoming the tumor MDR.
化疗存在一些局限性，如生物利用度差、血液清除速度快、细胞摄取能力差、肿瘤积累低、对健康组织的严重副作用，最重要的是癌细胞的多药耐药性（MDR）。如今，已经开发出一系列基于两亲性药物偶联物（ADCs）的智能药物递送系统（DDS）来解决这些问题，包括聚合物-药物偶联物（PDC）、模拟磷脂的前药、肽-药物偶联物（PepDCs）、纯纳米药物（PND）、两亲性药物-药物偶联物（ADDC）和双面药物-药物偶联物（JDDC）。这些 ADC 可以通过最小化赋形剂的净含量自组装成纳米颗粒（NPs）或微泡（MBs），实现隐身行为和物理完整性、高载药含量、无早期泄漏、长血液循环时间、固定药物组合和控制药物释放动力学等目标。此外，这些自组装系统可以进一步用于装载额外的治疗剂和成像造影剂，以进行联合治疗、体内肿瘤靶向的个性化监测以及药物药代动力学预测治疗效果。在这篇综述中，我们将总结基于 ADC 的联合化疗的最新进展，并讨论克服肿瘤 MDR 的重要作用。
