title: Potent tumor targeting drug release system comprising MMP-2 specific peptide fragment with self-assembling characteristics.
abstract: Self-assembling peptides are capable of forming a complex containing a cavity where cytotoxic agents can be wrapped in a self-assembling manner. These complexes are beneficial for improving the pharmacological properties and pharmacokinetics of cytotoxic agents, such as doxorubicin and paclitaxel. In the present study, this self-assembling feature was successfully integrated into a hexapeptide with matrix metalloproteinase (MMP)-2 specific targeting activity, producing a supramolecule possessing controlled drug release characteristics. The MMP-2 specific substrate fragment, PVGLIG, makes this supramolecule disassociate in the presence of MMP-2, and this system is considered to be a powerful tool for the treatment of tumors with high expression of MMP-2 or tumor metastasis. Our findings show that this modified self-assembling peptide with the PVGLIG fragment was able to significantly enhance specificity against HT1080 cells, a tumor cell line with high expression of MMP-2. In addition, residence time of the complex in blood was prolonged since paclitaxel was wrapped into the supramolecule. Our results suggest that the modified MMP-2 specific substrate, SAMTA7, could act as a controlled and sustained drug carrier for treatment of tumors with high expression of MMP-2 and for tumor metastasis.
authors.affiliation: School of Pharmacy, Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Hua
authors.affiliation: Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin, People's Republic of China.
authors.forename: Weiling
authors.initials: W
authors.lastname: Kong
authors.affiliation: Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin, People's Republic of China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin, People's Republic of China.
authors.forename: Zhixing
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.affiliation: Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin, People's Republic of China.
authors.forename: Yazhou
authors.initials: Y
authors.lastname: Li
authors.affiliation: Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin, People's Republic of China.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin, People's Republic of China.
authors.forename: Changxiao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin, People's Republic of China.
authors.forename: Lida
authors.initials: L
authors.lastname: Tang
authors.affiliation: Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Tianjin Institute of Pharmaceutical Research, State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Gong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D056004:Molecular Dynamics Simulation; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D010446:Peptide Fragments; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: drug targeting system; matrix metalloproteinase; paclitaxel; self-assembly