title: Anticancer activity of PEGylated matrix metalloproteinase cleavable peptide-conjugated adriamycin against malignant glioma cells.
abstract: Although matrix metalloproteinases (MMPs) play a crucial role in the invasion and growth of malignant gliomas, their increased activity in tumor environment can be used as a specific target for chemotherapy. We investigated whether polymer-drug conjugates formed via MMP-cleavable peptide linkages could provide MMP-responsive tumor targeting and cytotoxicity for malignant glioma cells. One end of an MMP-cleavable peptide was attached to the end of methoxy polyethylene glycol (MPEG) while the other end was attached to adriamycin (ADR). The release of drugs in the presence of conditioned media of U87MG cells was investigated. The cytotoxicities of the MMP-cleavable MPEG-peptide-ADR (PPA) conjugates and non-cleavable MPEG-ADR (PA) conjugates were investigated using U87MG cells. The (1)H nuclear magnetic resonance (NMR) spectra confirmed the conjugation of the two ends of the peptide to the ends of MPEG and ADR, respectively. Gelatin zymography showed that MMP-2 was strongly expressed in the media of U87MG cells. The PA conjugate did not release ADR either in the phosphate buffered saline (PBS) or conditioned media of U87MG cells. The PPA conjugate released ADR in the presence of the conditioned media of U87MG cells, but not in PBS only. In the cytotoxicity test using U87MG cells, ADR and PPA conjugate showed similar anti-proliferative activities, while the cytotoxicity of PA conjugate was lower than that of ADR. Considering that the cytotoxicity of the PPA conjugate was similar to that of ADR, MMP-cleavable polymer-drug conjugates can be used as targeting carriers for the purpose of inhibiting the proliferation of malignant glioma cells.
authors: Department of Neurosurgery, Chonnam National University Hwasun Hospital & Medical School, Republic of Korea.
authors: Seung-Ho
authors: SH
authors: Lim
authors: Young-Il
authors: YI
authors: Jeong
authors: Kyung-Sub
authors: KS
authors: Moon
authors: Hyang-Hwa
authors: HH
authors: Ryu
authors: Yong-Hao
authors: YH
authors: Jin
authors: Shu-Guang
authors: SG
authors: Jin
authors: Tae-Young
authors: TY
authors: Jung
authors: In-Young
authors: IY
authors: Kim
authors: Sam-Suk
authors: SS
authors: Kang
authors: Shin
authors: S
authors: Jung
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D011092:Polyethylene Glycols; D004317:Doxorubicin; D020782:Matrix Metalloproteinases