用于高效递送抗癌药物的新型木质素基靶向聚合物纳米颗粒平台的开发。
Development of Novel Lignin-Based Targeted Polymeric Nanoparticle Platform for Efficient Delivery of Anticancer Drugs.
作者信息
Liu Kefeng, Zheng Dan, Lei Hantian, Liu Jing, Lei Jiandu, Wang Luying, Ma Xingyuan
机构信息
Beijing Key Laboratory of Lignocellulosic Chemistry, Beijing Forestry University, Beijing 100083, P. R. China.
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, P. R. China.
出版信息
ACS Biomater Sci Eng. 2018 May 14;4(5):1730-1737. doi: 10.1021/acsbiomaterials.8b00260. Epub 2018 Apr 4.
The clinical applications of natural anticancer drugs are being restricted by poor water solubility, fast clearance in the circulation, lack of targeting to tumor cells, and poor tissue penetration. To address these problems, in this study, we developed a novel lignin-based targeted polymeric nanoparticles (NPs) platform, folic acid-polyethylene glycol-alkaline lignin conjugates (FA-PEG-AL), via self-assembly for delivery of anticancer drug (hydroxyl camptothecin, HCPT). These lignin-based nanoparticles had moderate particle size (∼150 nm) with a narrow size distribution (PDI < 0.1), exhibited excellent biocompatibility, high drug loading efficiency (∼24.2 wt % of HCPT), prolonged blood circulation time (∼7-fold of free HCPT), and enhanced cellular uptake (∼5-fold of free HCPT). Besides, the drug biodistribution study confirmed preferred accumulation of FA-PEG-AL/HCPT NPs in tumor tissue. Subsequent tumor xenograft test revealed superior tumor suppression efficacy and reduced side effects of FA-PEG-AL/HCPT NPs compared with free HCPT. Therefore, the prepared lignin-based FA-PEG-AL/HCPT NPs would be a promising candidate for anticancer drugs delivery.
天然抗癌药物的临床应用受到水溶性差、在循环系统中快速清除、缺乏对肿瘤细胞的靶向性以及组织穿透性差等因素的限制。为了解决这些问题，在本研究中，我们通过自组装开发了一种新型的基于木质素的靶向聚合物纳米颗粒（NPs）平台，即叶酸-聚乙二醇-碱性木质素缀合物（FA-PEG-AL），用于递送抗癌药物（羟基喜树碱，HCPT）。这些基于木质素的纳米颗粒具有适中的粒径（约150 nm）和较窄的粒径分布（PDI < 0.1），表现出优异的生物相容性、高载药效率（约24.2 wt%的HCPT）、延长的血液循环时间（约为游离HCPT的7倍）以及增强的细胞摄取（约为游离HCPT的5倍）。此外，药物生物分布研究证实FA-PEG-AL/HCPT NPs在肿瘤组织中优先积累。随后的肿瘤异种移植试验表明，与游离HCPT相比，FA-PEG-AL/HCPT NPs具有优异的肿瘤抑制效果和更低的副作用。因此，所制备的基于木质素的FA-PEG-AL/HCPT NPs有望成为抗癌药物递送的候选物。
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