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

Abstract

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.