Journal
ONCOTARGET
Volume 7, Issue 32, Pages 52230-52238Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.10735
Keywords
matrix metalloproteinase; tumor targeting peptide; drug conjugate; paclitaxel; tumor metastasis
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Funding
- National Science and Technology Major Project of the Ministry of Science and Technology of China [2014ZX09507005-003]
- National Natural Science Funding [81400932]
- Major Project of Science and Technology of Tianjin [13RCGFSY19700]
- Natural Science Foundation of Tianjin, China [12JCYBJC31500]
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Peptide drug conjugates offer a novel strategy to achieve controlled drug release. This approach avoids the clinical obstacles of non-specific toxicity and overall drug resistance of conventional cytotoxic agents, such as paclitaxel. MMP2 plays important functions in tumour proliferation and metastasis. Herein, we conjugated the paclitaxel with a hexapeptide which is specific recognized by MMP2 protein. The conjugate is dissociated upon the MMP2 specific proteolysis at COOH terminal of hexapeptide, PVGLIG. The results clearly indicated that the PVGLIG-paclitaxel conjugate significantly enhanced the tumor specificity against HT-1080 and U87-MG tumour cells. Our finding suggested that the hexapeptide PVGLIG is capable to act as a controlled and sustained drug carrier of paclitaxel for the treatment against tumour proliferation and metastasis with high MMP2 expression.
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