| RRC ID |
43013
|
| Author |
Hatakeyama H, Akita H, Ishida E, Hashimoto K, Kobayashi H, Aoki T, Yasuda J, Obata K, Kikuchi H, Ishida T, Kiwada H, Harashima H.
|
| Title |
Tumor targeting of doxorubicin by anti-MT1-MMP antibody-modified PEG liposomes.
|
| Journal |
Int J Pharm
|
| Abstract |
Immunoliposomes are potent carriers for targeting of therapeutic drugs to specific cells. Membrane type-1 matrix metalloproteinase (MT1-MMP), which plays an important role in angiogenesis, is expressed on angiogenic endothelium cells as well as tumor cells. Then, the MT1-MMP might be useful as a target molecule for tumor and neovascularity. In the present study, we addressed a utility of antibodies against the MT1-MMP as a targeting ligand of liposomal anticancer drug. Fab' fragments of antibody against the MT1-MMP were modified at distal end of polyethylene glycol (PEG) of doxorubicin (DXR)-encapsulating liposomes, DXR-sterically stabilized immunoliposomes (DXR-SIL[anti-MT1-MMP(Fab')]). Modification with the antibody significantly enhanced cellular uptake of DXR-SIL[anti-MT1-MMP(Fab')] into the HT1080 cells, which highly express MT1-MMP, compared with the non-targeted liposomes (DXR-stealthliposomes (DXR-SL)), suggesting that MT1-MMP antibody (Fab') is a potent targeting ligand for the MT1-MMP expressed cells. In vivo systemic administration of DXR-SIL[anti-MT1-MMP(Fab')] into the tumor-bearing mice showed significant suppression of tumor growth compared to DXR-SL. This is presumably due to the active targeting of immunoliposomes for tumor and neovascularity. However, tumor accumulation of DXR-SIL[anti-MT1-MMP(Fab')] and DXR-SL were comparable, suggesting that both liposomal formulations accumulated in tumor via enhanced permeation and retention (EPR) effect, but not via targeting to the MT1-MMP expressed on both the endothelial and tumor cells. It appears that the enhanced antitumor activity of DXR-SIL[anti-MT1-MMP(Fab')] resulted from acceleration of cellular uptake of lioposomes owing to the incorporated antibody after extravasation from capillaries in tumor.
|
| Volume |
342(1-2)
|
| Pages |
194-200
|
| Published |
2007-9-5
|
| DOI |
10.1016/j.ijpharm.2007.04.037
|
| PII |
S0378-5173(07)00361-4
|
| PMID |
17583453
|
| MeSH |
Animals
Antibiotics, Antineoplastic / administration & dosage
Antibiotics, Antineoplastic / therapeutic use*
Antibodies, Monoclonal / chemistry
Antibodies, Monoclonal / pharmacology
Doxorubicin / administration & dosage
Doxorubicin / therapeutic use*
Drug Compounding
Drug Delivery Systems
Excipients
Immunochemistry
Immunoglobulin Fab Fragments / chemistry
Liposomes
Male
Matrix Metalloproteinase 14 / immunology*
Mice
Mice, Inbred BALB C
Neoplasms, Experimental / drug therapy
Neoplasms, Experimental / metabolism
Polyethylene Glycols / chemistry
|
| IF |
4.845
|
| Times Cited |
127
|
|
WOS Category
|
PHARMACOLOGY & PHARMACY
|
| Resource |
| Human and Animal Cells |
|
