Drug-Bearing Supramolecular MMP Inhibitor Nanofibers for Inhibition of Metastasis and Growth of Liver Cancer

作者：Ji, Yujie; Xiao, Yanyu; Xu, Liu; He, Jiayu; Qian, Chen; Li, Weidong; Wu, Li; Chen, Rui; Wang, Jingjing; Hu, Rongfeng; Zhang, Xudong; Gu, Zhen; Chen, Zhipeng^*

来源：Advanced Science, 2018, 5(8): 1700867.

DOI：10.1002/advs.201700867

• doxorubicin
• liver cancer
• metastasis
• matrix metalloproteinase (MMP) inhibitor
• peptide drug conjugates

Treatment of hepatocellular carcinoma (HCC) requires sustained suppression of tumor cell growth and metastasis for long-term efficacy. However, traditional intratumoral drug delivery system always exhibits burst release with less therapeutic outcomes. Here, a new self-assembling amphiphilic peptide drug conjugate (SAAPDC) is fabricated as a two-in-one nanofiber system comprising a hexapeptide as a matrix metalloproteinases (MMP) inhibitor and doxorubicin (DOX) for the treatment of HCC. The results indicate that doxorubicin-conjugated peptide (DOX-KGFRWR) self-assembles to form long nanofibers showing sustained release property for inhibiting the enzymatic activities of MMP-2 and MMP-9. This nanofiber not only inhibits tumor growth in situ but also effectively prevents pulmonary metastasis in an SMMC7721 cell line-based mouse model. In summary, this hexapeptide-based supermolecule system represents a promising nanoscale platform to sustain drug release with high loading capacity for intratumoral administration. Moreover, the delivery of chemotherapeutic drugs via drug-bearing supramolecular MMP inhibitor nanofibers simultaneously inhibits metastasis and tumor growth to achieve synergistic effects for metastatic HCC therapy.

• 出版日期2018-8
• 单位南京中医药大学; 中国药科大学; 安徽中医药大学