Department of Emergency, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Department of Gastroenterology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China.
Curr Med Sci. 2020 Feb;40(1):145-154. doi: 10.1007/s11596-020-2158-4. Epub 2020 Mar 13.
Developing the methodologies that allow for safe and effective delivery of therapeutic drugs to target sites is a very important research area in cancer therapy. In this study, polyethylene glycol (PEG)-coated magnetic polymeric liposome (MPL) nanoparticles (NPs) assembled from octadecyl quaternized carboxymethyl chitosan (OQC), PEGylated OQC, cholesterol, and magnetic NPs, and functionalized with epithelial growth factor receptor (EGFR) peptide, were successfully prepared for in-vivo liver targeting. The two-step liver targeting strategy, based on both magnetic force and EGFR peptide conjugation, was evaluated in a subcutaneous hepatocellular carcinoma model of nude mouse. The results showed that EGFR-conjugated MPLs not only accumulated in the liver by magnetic force, but could also diffuse into tumor cells as a result of EGFR targeting. In addition, paclitaxel (PTX) was incorporated into small EGFR-conjugated MPLs (102.0±0.7 nm), resulting in spherical particles with high drug encapsulation efficiency (>90%). The use of the magnetic targeting for enhancing the transport of PTX-loaded EGFR-conjugated MPLs to the tumor site was further confirmed by detecting PTX levels. In conclusion, PTX-loaded EGFR-conjugated MPLs could potentially be used as an effective drug delivery system for targeted liver cancer therapy.
开发能够将治疗药物安全有效地递送到靶部位的方法是癌症治疗中一个非常重要的研究领域。在本研究中，成功制备了由十八烷基季铵化羧甲基壳聚糖（OQC）、聚乙二醇化 OQC、胆固醇和磁性纳米颗粒组装而成的聚乙二醇（PEG）包覆磁性聚合物脂质体（MPL）纳米颗粒（NPs），并通过上皮生长因子受体（EGFR）肽进行功能化，用于体内肝脏靶向。基于磁力和 EGFR 肽缀合的两步肝脏靶向策略在裸鼠皮下肝癌模型中进行了评估。结果表明，EGFR 缀合的 MPL 不仅可以通过磁力聚集在肝脏中，还可以通过 EGFR 靶向扩散到肿瘤细胞中。此外，紫杉醇（PTX）被包裹在小的 EGFR 缀合的 MPLs（102.0±0.7nm）中，形成具有高药物包封效率（>90%）的球形颗粒。通过检测 PTX 水平进一步证实了磁靶向用于增强载 PTX 的 EGFR 缀合 MPLs 向肿瘤部位的输送。总之，载 PTX 的 EGFR 缀合 MPLs 可能成为靶向肝癌治疗的有效药物递送系统。
