title: Controlled release strategy of paclitaxel by conjugating to matrix metalloproteinases-2 sensitive peptide.
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.
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.|Tianjin Institute of Pharmaceutical Research, Tianjin, China.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Huang
authors.affiliation: Tianjin Institute of Pharmaceutical Research, Tianjin, China.
authors.forename: Xiulin
authors.initials: X
authors.lastname: Yi
authors.affiliation: School of Pharmacy, Tianjin Medical University, Tianjin, China.
authors.forename: Dexin
authors.initials: D
authors.lastname: Kong
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University, Tianjin, China.
authors.forename: Ligong
authors.initials: L
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Tianjin Medical University, Tianjin, China.|Department of Oncology, University of Oxford, Oxford, UK.
authors.forename: Gong
authors.initials: G
authors.lastname: Min
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D017239:Paclitaxel / Q000008:administration & dosage*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D010455:Peptides; D020778:Matrix Metalloproteinase 2; D017239:Paclitaxel
keywords: drug conjugate; matrix metalloproteinase; paclitaxel; tumor metastasis; tumor targeting peptide