Abstract
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.
Highlights
Matrix metalloproteinases (MMPs) are well known, as they play important functions in tumour proliferation and metastasis [1,2,3]
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
Many studies have demonstrated that overexpression of MMP2 and MMP9 plays a vital role in metastatic tumour cells, promoting tumour growth and angiogenesis in the tumour, thereby providing nutrition to the tumour through the newly generated vessels [4,5,6,7]
Summary
Matrix metalloproteinases (MMPs) are well known, as they play important functions in tumour proliferation and metastasis [1,2,3]. MMP2 inhibitors prevented tumor dissemination and the formation of metastases by antiangiogenic properties [8,9,10,11,12]. The specific protease activity of MMPs has made it an attractive approach for controlling drug release. The prodrug is dissociated with the peptides by proteolysis of MMPs. Recently, several MMP associated PDCs have been developed in order to improve the tumor specificity of small chemical agents, including paclitaxel, doxorubicin, methotrexate and so on [16, 17]. In contrast to the original therapeutic approach of using small molecular inhibitors of MMPs, these novel drug-targeting strategies resulted in an improved therapeutic index and less toxicity [18,19,20]
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