Controlled release strategy of paclitaxel by conjugating to matrix metalloproteinases-2 sensitive peptide

// Changjiang Huang 1, 2 , Xiulin Yi 2 , Dexin Kong 3 , Ligong Chen 1 , Gong Min 3, 4 1 School of Chemical Engineering and Technology, Tianjin University, Tianjin, China 2 Tianjin Institute of Pharmaceutical Research, Tianjin, China 3 School of Pharmacy, Tianjin Medical University, Tianjin, China 4 Department of Oncology, University of Oxford, Oxford, UK Correspondence to: Gong Min, email: kahongmg@163.com Ligong Chen, email: lgchen@tju.edu.cn Keywords: matrix metalloproteinase, tumor targeting peptide, drug conjugate, paclitaxel, tumor metastasis Received: April 25, 2016      Accepted: May 29, 2016      Published: July 20, 2016 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.