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.

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

“…In designer self‐assembling peptide hydrogels, the canonical amino acid residues serve as basic molecular building blocks of nanofiber scaffold networks, which confer inherent biocompatibility, high hydrophilicity, chemical amenability, and biodegradation in vivo. Because of these prominent advantages, designer self‐assembling peptide hydrogels are proposed to fabricate various 3D ex vivo microtissue models, [ 65 ] tumor organoids for preclinical drug discovery, [ 80 ] 3D cell culture constructs for clinical drug repositioning, [ 3 ] therapeutic drug or cell delivery carrier, [ 66b,81 ] and new generation self‐adjuvant vaccine design. [ 82 ] Over the past decades, extensive biomedical researches and translational and clinical trials greatly enlarged our understanding of basic cancer research.…”

<p>Nanocarrier-Based Therapeutics and Theranostics Drug Delivery Systems for Next Generation of Liver Cancer Nanodrug Modalities</p>

“…34 Ji et al, (2018) synthesized doxorubicin-conjugated nanofibers which have the property of sustained release drug for inhibiting tumor growth in an SMMC7721 cell line in the mouse model. 35 Liu et al (2013) investigated a doxorubicin-loaded nanofiber as a chemotherapeutic system against hepatic carcinoma. They observed significant anti-tumor efficacy in the resulting nanofiber.…”

From Nanofibers to Nanorods: Nanostructure of Peptide‐Drug Conjugates Regulated by Polypeptide‐PEG Derivative and Enhanced Antitumor Effect

“…The PDC molecule KGFRWR‐DOX, which can assemble into nanofiber‐like hydrogels used for intratumor injection, can inhibit matrix metalloproteinase and thereby the metastasis and growth of liver cancer . For morphological regulation, PPD molecules were added to the KGFRWR‐DOX solution, and the mixture was ultrasonicated and stirred overnight for coassembly.…”

“…Construction and Characteristics of MNRs : The PDC used in this study was KGFRWR‐DOX, which was synthesized in the previous study . An appropriate amount of KGFRWR‐DOX and PPD was dissolved in distilled water, and different ratios of the two solutions were mixed by ultrasonication for 1 min.…”