MCBB Graduate Program and Department of Biology, Boston University, Boston, Massachusetts 02215, United States.
Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, United States.
Biomacromolecules. 2020 Apr 13;21(4):1499-1506. doi: 10.1021/acs.biomac.0c00064. Epub 2020 Mar 6.
Expansile nanoparticles (eNPs) are a promising pH-responsive polymeric drug delivery vehicle, as demonstrated in multiple intraperitoneal cancer models. However, previous delivery routes were limited to intraperitoneal injection and to a single agent, paclitaxel. In this study, we preliminarily evaluate the biodistribution and in vivo toxicity of eNPs in mice after intravenous injection. The eNPs localize predominantly to the liver, without detectable acute toxicity in the liver or other key organs. On the basis of these results, we encapsulated FQI1, a promising lead compound for treatment of hepatocellular carcinoma, in eNPs. eNPs are taken up by cancerous and noncancerous human liver cells in vitro, although at different rates. FQI1-loaded eNPs release FQI1 in a pH-dependent manner and limit proliferation equivalently to unencapsulated FQI1 in immortalized hepatocytes in vitro. eNPs are a versatile platform delivery system for therapeutic compounds and have potential utility in the treatment of liver disease.
膨胀纳米颗粒 (eNPs) 是一种有前途的 pH 响应性聚合物药物递送载体,在多种腹腔内癌症模型中得到了证实。然而,以前的给药途径仅限于腹腔内注射和单一药物紫杉醇。在这项研究中,我们初步评估了 eNPs 在静脉注射后小鼠体内的分布和体内毒性。eNPs 主要定位于肝脏,在肝脏或其他关键器官中没有检测到急性毒性。基于这些结果,我们将一种有前途的治疗肝细胞癌的先导化合物 FQI1 包封在 eNPs 中。eNPs 在体外被癌细胞和非癌细胞人肝实质细胞摄取,尽管摄取率不同。FQI1 负载的 eNPs 以 pH 依赖性方式释放 FQI1,并在体外抑制永生化肝细胞增殖的效果与未包封的 FQI1 相当。eNPs 是一种多功能的治疗化合物递送系统,在治疗肝脏疾病方面具有潜在的应用价值。