| 摘要 |
A pH-sensitive immunoliposome is provided to improve steric stability, increase retention time in blood, and enhance anti-cell proliferation and cell-killing effects, so that it is useful for selective delivery of anticancer drugs to cancer cells. The pH-sensitive immunoliposome consists of dioleoyl phosphatidylethanolamine(DOPE) and cholesterylhemisuccinate(CHEMS) in a mole ratio of 6:4, and is characterized by binding to a monoclonal antibody, wherein the monoclonal antibody is an epidermal growth factor receptor(EGFR). A method for preparing the pH-sensitive immunoliposome comprises the steps of: (1) reacting alpha-amino-Ћ-hydroxy polyethylene glycol with N-succineimidyl-3-(2-pyridyldithio)propionate(SPDP) to prepare pyridylthiopropionylamino-polyethyleneglycol-hydroxy(PDP-PEG-OH), treating PDP-PEG-OH with disuccine imidylate(DSC) and pyridine to prepare pyridylthiopropionylamino-polyethyleneglycol-disuccineimidylate (PDP-PEG-SC), and reacting PDP-PEG-SC with dioleoylphosphatidylethanolamine(DOPE) and triethylamine to prepare pyridylthiopropionylamino-polyethyleneglycol-dioleoylphosphatidylethanolamine(PDP-PEG-DOPE); (2) mixing PDP-PEG-DOPE with cholesterylhemisuccinate(CHEMS) in a mole ratio of 6:4 to prepare pyridylthiopropionylamino-polyethyleneglycol-pH sensitive liposome(PDP-PEG-PSL); and (3) adding dithiothreito into PDP-PEG-PSL to prepare thiol-polyethylene glycol-pH sensitive liposome(SH-PEG-PSL), and mixing SH-PEG-PSL with the monoclonal antibody derived from maleimidophenylbutyrate(MPB-Ab).
|
