Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA, USA.
Department of Pathobiology, College of Veterinary Medicine, Auburn University, AL, USA.
Nanomedicine. 2014 Feb;10(2):421-30. doi: 10.1016/j.nano.2013.08.009. Epub 2013 Sep 9.
A novel strategy to improve the therapeutic index of chemotherapy has been developed by the integration of nanotechnology with phage technique. The objective of this study was to combine phage display, identifying tumor-targeting ligands, with a liposomal nanocarrier for targeted delivery of doxorubicin. Following the proof of concept in cell-based experiments, this study focused on in vivo assessment of antitumor activity and potential side-effects of phage fusion protein-modified liposomal doxorubicin. MCF-7-targeted phage-Doxil treatments led to greater tumor remission and faster onset of antitumor activity than the treatments with non-targeted formulations. The enhanced anticancer effect induced by the targeted phage-Doxil correlated with an improved tumor accumulation of doxorubicin. Tumor sections consistently revealed enhanced apoptosis, reduced proliferation activity and extensive necrosis. Phage-Doxil-treated mice did not show any sign of hepatotoxicity and maintained overall health. Therefore, MCF-7-targeted phage-Doxil seems to be an active and tolerable chemotherapy for breast cancer treatment.
The authors of this study successfully combined phage display with a liposomal nanocarrier for targeted delivery of doxorubicin using MCF-7-targeted phage-Doxil nanocarriers in a rodent model. The method demonstrated improved efficiency and reduced hepatotoxicity, paving the way to future clinical trials addressing breast cancer.
通过将纳米技术与噬菌体技术相结合，开发了一种提高化疗治疗指数的新策略。本研究的目的是将噬菌体展示技术，鉴定肿瘤靶向配体，与脂质体纳米载体结合，用于阿霉素的靶向递药。在细胞实验中证明了概念的可行性后，本研究集中于评估噬菌体融合蛋白修饰的脂质体阿霉素的体内抗肿瘤活性和潜在副作用。与非靶向制剂相比， MCF-7 靶向噬菌体-Doxil 治疗导致更大的肿瘤缓解和更快的抗肿瘤活性。靶向噬菌体-Doxil 诱导的增强抗癌作用与阿霉素在肿瘤中的蓄积增加相关。肿瘤切片始终显示出增强的细胞凋亡、减少的增殖活性和广泛的坏死。接受噬菌体-Doxil 治疗的小鼠没有任何肝毒性迹象，并且保持整体健康。因此， MCF-7 靶向噬菌体-Doxil 似乎是一种用于乳腺癌治疗的有效且耐受良好的化疗药物。
本研究的作者成功地将噬菌体展示技术与脂质体纳米载体相结合，使用 MCF-7 靶向噬菌体-Doxil 纳米载体在啮齿动物模型中进行阿霉素的靶向递药。该方法提高了效率，降低了肝毒性，为未来针对乳腺癌的临床试验铺平了道路。
