Abstract: A monomer containing hexa-thiols (C-6SH) was obtained through the reduction of the precursor N, N', N"-tris-lipoic amides of tris(2-aminoethyl) amine and then modified with (6-maleimidocaproyl) hydrazone of doxorubicin(DOX)(MAL-DOX). By using ethylene diacrylate (EGDMA) as crosslinker, core-crosslinked nanoparticles were synthesized with polyethylene glycol (PEG) shells and pH-sensitive drug delivery via click reactions of thiol-acrylate. The size and morphology of nanoparticles were determined by Dynamic Light Scattering (DLS) and Transmission Electron Microscope (TEM). Results showed that the nanoparticles had a spherical morphology with average diameter of 42 nm. In vitro drug release studies indicated that DOX conjugated nanoparticles with hydrazone bond showed a pH sensitive release phenomenon, that was, the releasing was significantly faster at mildly acidic condition with pH of 5.5 than that at physiological condition.