Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing 100193, China.
Research Center on Life Sciences and Environmental Sciences, Harbin University of Commerce, No. 138, Tongda Street, Daoli District, Harbin 150076, China.
Mol Pharm. 2020 Apr 6;17(4):1205-1214. doi: 10.1021/acs.molpharmaceut.9b01228. Epub 2020 Mar 3.
The composition of amphiphilic nanocarriers can affect the antitumor efficacy of drug-loaded nanoparticles and should be researched systematically. In this paper, to study the influence of hydrophobic chains, an amphiphilic copolymer (PEGPCL) and hydrophilic PEG (PEG) were utilized as nanocarriers to prepare docetaxel-loaded nanoparticles (DTX/PEGPCL nanoparticles and DTX/PEG nanoparticles) through an antisolvent precipitation method. The two DTX nanoparticles presented a similar drug loading content of approximately 60% and a sheet-like morphology. During the preparation procedure, the drug loading content affected the morphology of DTX nanoparticles, and the nanocarrier composition influenced the particle size. Compared with DTX/PEG nanoparticles, DTX/PEGPCL nanoparticles showed a smaller mean diameter and better in vitro and in vivo antitumor activity. The cytotoxicity of DTX/PEGPCL nanoparticles against 4T1 cells was 1.31 μg mL, 3.4-fold lower than that of DTX/PEG nanoparticles. More importantly, DTX/PEGPCL nanoparticles showed significantly higher antitumor activity in vivo, with an inhibition rate over 80%, 1.5-fold higher than that of DTX/PEG nanoparticles. Based on these results, antitumor activity appears to be significantly affected by the particle size, which was determined by the composition of the nanocarrier. In summary, to improve antitumor efficacy, the amphiphilic structure should be considered and optimized in the design of nanocarriers.
两亲性纳米载体的组成会影响载药纳米粒的抗肿瘤疗效，应该进行系统的研究。在本文中，为了研究疏水性链的影响，采用两亲性共聚物（PEGPCL）和亲水性 PEG（PEG）作为纳米载体，通过抗溶剂沉淀法制备了负载多西紫杉醇的纳米粒（DTX/PEGPCL 纳米粒和 DTX/PEG 纳米粒）。两种 DTX 纳米粒的载药含量相近，约为 60%，呈片状形态。在制备过程中，载药量影响 DTX 纳米粒的形态，而纳米载体的组成影响粒径。与 DTX/PEG 纳米粒相比，DTX/PEGPCL 纳米粒具有更小的平均粒径和更好的体外和体内抗肿瘤活性。DTX/PEGPCL 纳米粒对 4T1 细胞的细胞毒性为 1.31μg mL，比 DTX/PEG 纳米粒低 3.4 倍。更重要的是，DTX/PEGPCL 纳米粒在体内表现出显著更高的抗肿瘤活性，抑制率超过 80%，比 DTX/PEG 纳米粒高 1.5 倍。基于这些结果，抗肿瘤活性似乎受到粒径的显著影响，而粒径是由纳米载体的组成决定的。总之，为了提高抗肿瘤疗效，在纳米载体的设计中应考虑并优化其两亲性结构。
