Tian Jing, Min Yuangzeng, Rodgers Zachary, Wan Xiaomeng, Qiu Hui, Mi Yu, Tian Xi, Wagner Kyle T, Caster Joseph M, Qi Yanfei, Roche Kyle, Zhang Tian, Cheng Jianjun, Wang Andrew Z
School of Biological and Environmental Engineering, Tianjin Vocational Institute, Tianjin, PR China; Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Laboratory of Nano- and Translational Medicine, Lineberger Comprehensive Cancer Center, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Nanomedicine. 2017 Apr;13(3):1301-1307. doi: 10.1016/j.nano.2016.11.007. Epub 2016 Nov 21.
The combination chemotherapy regimen of cisplatin (CP) and docetaxel (DTX) is effective against a variety of cancers. However, combination therapies present unique challenges that can complicate clinical application, such as increases in toxicity and imprecise exposure of tumors to specific drug ratios that can produce treatment resistance. Drug co-encapsulation within a single nanoparticle (NP) formulation can overcome these challenges and further improve combinations' therapeutic index. In this report, we employ a CP prodrug (CPP) strategy to formulate poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs carrying both CPP and DTX. The dually loaded NPs display differences in drug release kinetics and in vitro cytotoxicity based on the structure of the chosen CPP. Furthermore, NPs containing both drugs showed a significant improvement in treatment efficacy versus the free drug combination in vivo.
顺铂（CP）和多西他赛（DTX）联合化疗方案对多种癌症有效。然而，联合疗法存在独特的挑战，可能使临床应用复杂化，例如毒性增加以及肿瘤对特定药物比例的暴露不准确，从而产生治疗抗性。将药物共包封在单一纳米颗粒（NP）制剂中可以克服这些挑战，并进一步提高联合疗法的治疗指数。在本报告中，我们采用CP前药（CPP）策略来制备同时携带CPP和DTX的聚（乳酸-共-乙醇酸）-聚（乙二醇）（PLGA-PEG）纳米颗粒。基于所选CPP的结构，双重负载的纳米颗粒在药物释放动力学和体外细胞毒性方面表现出差异。此外，与游离药物组合相比，含有两种药物的纳米颗粒在体内的治疗效果有显著改善。
