Development of targeted therapy with paclitaxel incorporated into EGF-conjugated nanoparticles.

Abstract

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.

MATERIALS AND 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.

CONCLUSION:

These results suggest that EGF-PMBN-PTX may represent a more potent targeted therapy for tumors overexpressing EGFR.

• Authors: Toshiyuki Shimada, Masakazu Ueda, Hiromitsu Jinno, Naokazu Chiba, Masahiro Wada, Junji Watanabe, Kazuhiko Ishihara, Yuko Kitagawa
• Journal: Anticancer research (Anticancer Res) Vol. 29 Issue 4 Pg. 1009-14 (Apr 2009) ISSN: 0250-7005 [Print] Greece
• PMID: 19414339 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Methacrylates
• Phosphorylcholine
• 2-methacryloyloxyethyl phosphorylcholine
• Epidermal Growth Factor
• ErbB Receptors
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacokinetics)
• Breast Neoplasms (drug therapy, pathology)
• Drug Delivery Systems
• Epidermal Growth Factor (chemistry)
• ErbB Receptors (metabolism)
• Female
• Humans
• Infusions, Subcutaneous
• Methacrylates (chemistry)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles
• Paclitaxel (administration & dosage, pharmacokinetics)
• Phosphorylcholine (analogs & derivatives, chemistry)
• Tissue Distribution
• Tumor Cells, Cultured