†School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, China.
‡Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
ACS Appl Mater Interfaces. 2015 Apr 22;7(15):8005-12. doi: 10.1021/acsami.5b00329. Epub 2015 Apr 13.
Smac-conjugated nanoparticle (Smac-NP) was designed to induce the apoptosis of cancer cells and as a drug carrier for combination therapy. It contained three parts, a SmacN7 peptide which could induce apoptosis of cancer cells by interacting with XIAPs, the cell penetrating domain rich in arginine, and four hydrophobic tails for self-assembled Smac-NP. We demonstrated that Smac-NPs exerted an antitumor effect in breast cancer cell MDA-MB-231 and nonsmall lung cancer (NSCLC) cell H460, which efficiently inhibited cancer cells proliferation without influencing normal liver cell lines LO2. Smac-NPs also significantly induced apoptosis of MDA-MB-231 and H460 cells through activating pro-caspase-3, down-regulating the expression of antiapoptotic protein Bcl-2 and up-regulating the pro-apoptotic protein Bax. Furthermore, Smac-NPs could be explored as a drug delivery system to load hydrophobic drug such as DOX for combination therapy. The DOX-loaded nanoparticles (DOX-Smac-NPs) exhibited higher cellular uptake efficiency and antitumor effect. Our work provided a new insight into therapeutic peptides integrated with drug simultaneously in one system for cancer combination treatment.
Smac-缀合纳米颗粒（Smac-NP）旨在诱导癌细胞凋亡，并作为联合治疗的药物载体。它包含三个部分：SmacN7 肽，通过与 XIAPs 相互作用诱导癌细胞凋亡；富含精氨酸的细胞穿透结构域；以及四个疏水尾用于自组装 Smac-NP。我们证明 Smac-NPs 在乳腺癌细胞 MDA-MB-231 和非小细胞肺癌（NSCLC）细胞 H460 中发挥了抗肿瘤作用，它能够有效地抑制癌细胞增殖，而不影响正常肝细胞系 LO2。Smac-NPs 还通过激活前胱冬酶-3、下调抗凋亡蛋白 Bcl-2 的表达和上调促凋亡蛋白 Bax，显著诱导 MDA-MB-231 和 H460 细胞凋亡。此外，Smac-NPs 可以被探索作为一种药物递送系统，用于装载疏水性药物，如 DOX，进行联合治疗。载 DOX 的纳米颗粒（DOX-Smac-NPs）表现出更高的细胞摄取效率和抗肿瘤效果。我们的工作为将治疗性肽与药物同时整合到一个系统中进行癌症联合治疗提供了新的思路。
