Abstract

The aim of this study was to surface-functionalize PEGylated liposomal doxorubicin (PLD) using anti-p32 CGKRK peptide to evaluate its anti-angiogenic and anti-tumour activities. CGKRK was conjugated to DSPE-mPEG₂₀₀₀-maleimide and post-inserted into PLD at 25, 50, 100, 200 and 400 peptides per each liposome and characterised for their size, zeta potential, drug loading, release properties; and cell binding, cell uptake and cytotoxicity on three C26, 4T1 and human umbilical vein endothelial cell (HUVEC) cell lines. The in vitro results indicated the better efficiency of the PLD-100 (PLD with 100 CGKRK) formulation on 4T1 and HUVEC cell lines. The results of anti-tube formation and spheroid assay indicated the efficiencies of the PLD-100 formulation compared with Caelyx^® in vitro. The in vivo studies indicated the higher tumour accumulation of PLD-100 formulation in comparison with Caelyx^® which also implied the higher survival rates in mice treated with PLD-100 formulation. Histological evaluations demonstrated that PLD-100 had no side-effects on major organs. In conclusion, the results of this study indicated that PLD-CGKRK- could efficiently target endothelial and tumour parenchymal cells which enhance the therapeutic efficacy of PLD and merits further investigation.

摘要

本研究的目的是使用抗 p32 CGKRK 肽对聚乙二醇化脂质体阿霉素 (PLD) 进行表面功能化，以评估其抗血管生成和抗肿瘤活性。CGKRK 与 DSPE-mPEG _2000-马来酰亚胺结合，并以每个脂质体25、50、100、200和 400 个肽段后插入 PLD 并表征它们的大小、zeta 电位、载药量、释放特性；以及对三种 C26、4T1 和人脐静脉内皮细胞 (HUVEC) 细胞系的细胞结合、细胞摄取和细胞毒性。的体外结果表明所述PLD-100（PLD 100 CGKRK）上4T1和HUVEC细胞系制剂的更好的效率。抗管形成和球状体测定的结果表明 PLD-100 制剂与 Caelyx ^®相比的效率 体外。的体内研究表明与比较CAELYX PLD-100制剂的更高的肿瘤积累^®这也暗示与PLD-100制剂处理的小鼠中的更高的存活率。组织学评估表明 PLD-100 对主要器官没有副作用。总之，本研究结果表明，PLD-CGKRK-可有效靶向内皮细胞和肿瘤实质细胞，增强了PLD的治疗效果，值得进一步研究。