Development of targeted therapy with paclitaxel incorporated into EGF-conjugated nanoparticles.
BACKGROUND
2-Methacryloyloxyethyl phosphorylcholine (MPC) polymer is a suitable vehicle for paclitaxel (PTX) delivery. A new targeted therapy has been developed by conjugating epidermal growth factor (EGF) to MPC polymer and its growth inhibitory and antitumor effects on cancer cells overexpressing EGF receptors (EGFR) has been investigated.


METHODS
EGF was conjugated to poly [MPC-co-n-butyl methacrylate-co-p-nitrophenyloxycarbonyl poly (ethylene glycol) methacrylate] (PMBN) and mixed with PTX. The cytotoxicity of the resulting PTX incorporated into EGF-conjugated PMBN (EGF-PMBN-PTX) on EGFR-overexpressing and EGFR-deficient cell lines was compared with PTX incorporated into PMBN alone (PMBN-PTX) and PTX alone. Suspensions of the cells were injected into nude mice subcutaneously. EGF-PMBN-PTX, PMBN-PTX, PTX or NaCl solution was injected intraperitoneally.


RESULTS
The cytotoxicity and antitumor effect of EGF-PMBN-PTX were significantly greater than those of PMBN-PTX for EGFR-overexpressing cells but not for an EGFR-deficient line.


CONCLUSIONS
These results suggest that EGF-PMBN-PTX may represent a more potent targeted therapy for tumors overexpressing EGFR.
Shimada
Toshiyuki
T
Department of Surgery, Keio University School of Medicine, Tokyo, 160-8582, Japan.
Ueda
Masakazu
M
Jinno
Hiromitsu
H
Chiba
Naokazu
N
Wada
Masahiro
M
Watanabe
Junji
J
Ishihara
Kazuhiko
K
Kitagawa
Yuko
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016503:Drug Delivery Systems; D004815:Epidermal Growth Factor / Q000737:chemistry; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D055104:Infusions, Subcutaneous; D008689:Methacrylates / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D008689:Methacrylates; D010767:Phosphorylcholine; C070638:2-methacryloyloxyethyl phosphorylcholine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D017239:Paclitaxel