National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China.
Adv Healthc Mater. 2014 Aug;3(8):1299-308. doi: 10.1002/adhm.201300601. Epub 2014 Apr 6.
Peptide dendrimers have shown promise as an attractive platform for drug delivery. In this study, mPEGylated peptide dendrimer-doxorubicin (dendrimer-DOX) conjugate-based nanoparticle is prepared and characterized as an enzyme-responsive drug delivery vehicle. The drug DOX is conjugated to the periphery of dendrimer via an enzyme-responsive tetra-peptide linker Gly-Phe-Leu-Gly (GFLG). The dendrimer-DOX conjugate can self-assemble into nanoparticle, which is confirmed by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy studies. At equal dose, mPEGylated dendrimer-DOX conjugate-based nanoparticle results in significantly high antitumor activity, and induces apoptosis on the 4T1 breast tumor model due to the evidences from tumor growth curves, an immunohistochemical analysis, and a histological assessment. The in vivo toxicity evaluation demonstrates that nanoparticle substantially avoids DOX-related toxicities and presents good biosafety without obvious side effects to normal organs of both tumor-bearing and healthy mice as measured by body weight shift, blood routine test, and a histological analysis. Thus, the mPEGylated peptide dendrimer-DOX conjugate-based nanoparticle may be a potential nanoscale drug delivery vehicle for the breast cancer therapy.
肽树状大分子作为一种有吸引力的药物传递平台已经显示出了潜力。在这项研究中，制备了聚乙二醇化的肽树状大分子-阿霉素（dendrimer-DOX）缀合物纳米粒子，并将其作为一种酶响应型药物传递载体进行了表征。药物 DOX 通过酶响应四肽接头 Gly-Phe-Leu-Gly（GFLG）连接到树突状大分子的外围。树突状大分子-DOX 缀合物可以自组装成纳米粒子，这一点通过动态光散射、扫描电子显微镜和透射电子显微镜研究得到了证实。在相同剂量下，聚乙二醇化的树突状大分子-DOX 缀合物纳米粒子由于在 4T1 乳腺癌模型中的肿瘤生长曲线、免疫组织化学分析和组织学评估中显示出明显的抗肿瘤活性和诱导细胞凋亡的证据，表现出显著的抗肿瘤活性。体内毒性评估表明，纳米粒子在很大程度上避免了 DOX 相关的毒性，并表现出良好的生物安全性，对荷瘤和健康小鼠的正常器官没有明显的副作用，这一点可以通过体重变化、血常规检查和组织学分析来衡量。因此，聚乙二醇化的肽树状大分子-DOX 缀合物纳米粒子可能是一种用于乳腺癌治疗的潜在的纳米级药物传递载体。
