Abstract: An orthoester monomer of (2-(octadecyloxy)-1,3-dioxolan-4-yl) methanamine (OE) was synthesized using 3-amino-1,2-propanediol as starting material. A novel pH-sensitive polymer, mPEG-GDE-OE, was prepared by ring opening polymerization of OE, methoxypolyethylene glycol amine (mPEG-NH₂) and glycol diglycidyl ether (GDE). The pH-insensitive polymer, mPEG-GDE-OA, was synthesized as a reference polymer. Amphiphilic polymers (mPEG-GDE-OE and mPEG-GDE-OA) could self-assemble into micelles by solvent volatilization method. Then doxorubicin (DOX) was used as a model drug to incorporate into mPEG-GDE-OE and mPEG-GDE-OA micelles. These polymers were characterized by ¹H-NMR. The size and the morphologies of the micelles were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The drug release properties of micelles were investigated in vitro. Human breast cancer cells (MCF-7) and cervical cancer cells (Hela) were used as model tumor cell lines to investigate the cytotoxicity and antitumor activity of drug loaded polymer micelles in vitro. Results show that the particle sizes of mPEG-GDE-OE and mPEG-GDE-OA micelles are (168.2 ± 4.6) nm and (157.5 ± 3.4) nm, respectively. The particle sizes of drug-loaded micelles, DOX/mPEG-GDE-OE and DOX/mPEG-GDE-OA, are (191.6±6.7) nm and (182.8±5.2) nm, respectively. Compared with mPEG-GDE-OA micelles, mPEG-GDE-OE micelles have good pH sensitivity, good controlled release performance and strong tumor killing ability.