Abstract: Amphiphilic centipede-like copolymer and doxorubicin-loading nanoparticle were prepared through self-emulsification. Then, narrowly distributed poly(glycidyl methacrylate) (PGMA) was prepared through reversible addition-fragmentation-transfer (RAFT) polymerization and converted into PGMA with hydroxyl and azido group at each GMA unit (PGMA-OH/N₃). Thereafter, poly(ethylene glycol) capped with one alkynyl group (PEG-alk) was grafted onto PGMA backbone through click reaction to result in PGMA-OH/PEG, and poly(ε-caprolactone) (PCL) was grafted from PGMA via Sn(Oct)₂-initiated ring-opening polymerization of CL monomer. Thus, amphiphilic centipede-like copolymer of PGMA-g-PEG/PCL was successfully obtained, confirmed with proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy, Fourier Transfer Infra-red (FT-IR) spectroscopy and Gel Permeation Chromatography (GPC). Based on the amphiphilicity of PGMA-g-PEG/PCL, its self-emulsification in water-chloroform mixture could load doxorubicin (DOX) efficiently to form nanoparticles with averaged radius of about 100 nm, which was determined by Dynamic Light Scattering (DLS) and scanning electron microscopy after the evaporation of chloroform. With the aid of UV-Vis spectroscopy and DLS, the drug-released of those nanoparticles was performed in neutral and acidic aqueous solutions (pH=7.0 and 5.0). Results showed that higher release rate was achieved under acidic condition due to the degradation of PCL.