Polymeric graft polyphosphazene containing 4-aminobenzoic acid diethylaminoethyl ester (DEAAB) as hydrophobic side groups was rationally designed and named PDEP. PDEP can self-assemble into a nanovesicle in water. More importantly, when compared with the amphiphile poly[(methoxy-poly(ethylene glycol))(ethyl p-aminobenzoate)]phosphazene (PEP) copolymer containing benzene rings and the amphiphile poly[(methoxy-poly(ethylene glycol)(N,N-diisopropylethylenediamine)]phosphazene (PDP) copolymer containing tertiary amino groups, the coexistence of benzene and tertiary amino groups in PDEP enabled it to effectively load water-soluble small-molecule doxorubicin hydrochloride (DOXHCl) into the vesicle and efficiently induce in situ transformation of gold tetrachloroaurate (HAuCl4) to gold nanoparticles (AuNPs) as both a reductant and a stabilizer. By optimizing the reduction conditions, such as the temperature, reaction time, and hydrophobic group in polymer/HAuCl4 molar ratio, the AuNP complex PDEP vesicles significantly inhibited the DOXHCl burst release at pH 7.4 while displaying a fast release responsive to pH 5.5.