2005 Fiscal Year Final Research Report Summary
The development of a new drug delivery system using nanoparticles including paclitaxel, conjugated with anti-epidermal growth factor receptor (EGFR) monoclonal antibody.
| Project/Area Number |
16591353
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Keio University |
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Principal Investigator |
HASEGAWA Hirotoshi Keio University, School of Medicine, Lecturer, 医学部, 講師 (00218455)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Yoshiyuki Keio University, School of Medicine, Instructor, 医学部, 助手 (30255468)
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| Project Period (FY) |
2004 – 2005
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| Keywords | nanoparticle / missile therapy / paclitaxel / epidermal growth factor receptor antibody |
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| Research Abstract |
The purpose of this study was to develop a new drug delivery system for the anticancer agent to the cancer overexpressing epidermal growth factor receptor (EGFR). We used nanoparticles immobilized with 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer and including paclitaxel, conjugated with anti-EGFR monoclonal antibody (MAb 528). In vitro the cytotoxicities against the A431 cell line overexpressing the EGFR and the H69 cell line expressing no EGFR were assessed by MTT assay. Neither nanoparticles alone nor MAb 528 alone had the cytotoxicity to A431 or H69. The IC50 of paclitaxel on A431 was about 10 ng/ml, which was almost the same in the group of nanoparticles with paclitaxel non-conjugated with antibody. There were no differences in the cytotoxicity between the paclitaxel alone group and nanoparticles with paclitaxel non-conjugated with antibody. However, the IC50 on A431 was obtained with the lower concentration of paclitaxel about 3.45 ng/ml in the group of nanoparticles with paclitaxel conjugated with MAb 528 (p<0.001). There were no differences in the cytotoxicity to H69 among the paclitaxel alone, nanoparticles with paclitaxel non-conjugated and conjugated with MAb 528. The cytotoxicity was dependent on the level of the EGFR expression. These data suggested the possibility of the development of an effective, new drug deliver system.
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