Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, College of Polymer Science and Engineering, Sichuan University, Chengdu 610041, P. R. China.
Nanoscale. 2018 Jul 19;10(28):13673-13683. doi: 10.1039/c8nr03297a.
Prostate cancer, one of the leading causes of disease and death in men all over the world, is challenging to treat. α-Enolase, a multifunctional protein, is overexpressed on human prostate carcinoma cells, and thereby it is a potential target for treatment of prostate cancer. In the current study, the pHCT74 peptide was used to construct a kind of highly targeted liposome (pHCT74-lipo) loaded with doxorubicin (pHCT74-lipo-Dox), which specifically targeted α-enolase on prostate tumour cells. Compared with liposomes without pHCT74 modification, pHCT74-lipo-Dox displayed a superior intracellular internalization with enhanced tumour cytotoxicity. In the in vivo study, pHCT74-lipo showed much higher tumour accumulation. In addition, loaded into pHCT74-lipo, doxorubicin demonstrated significantly improved anti-tumour activity on prostate tumour-bearing mice. These results suggest that the pHCT74 peptide has potential to be used in the development of a novel drug delivery system for targeted therapy against prostate cancer.
前列腺癌是全世界男性疾病和死亡的主要原因之一，其治疗具有挑战性。烯醇酶-α是一种多功能蛋白，在人前列腺癌细胞中过表达，因此它是治疗前列腺癌的潜在靶点。在本研究中，pHCT74 肽被用于构建一种载有多柔比星的高度靶向脂质体（pHCT74-lipo-Dox），该脂质体特异性靶向前列腺肿瘤细胞上的烯醇酶-α。与没有 pHCT74 修饰的脂质体相比，pHCT74-lipo-Dox 显示出优越的细胞内内化作用，增强了肿瘤细胞毒性。在体内研究中，pHCT74-lipo 显示出更高的肿瘤积累。此外，载于 pHCT74-lipo 的多柔比星在荷瘤小鼠中表现出显著提高的抗肿瘤活性。这些结果表明，pHCT74 肽有可能被用于开发针对前列腺癌的新型靶向治疗药物递送系统。
