pH-responsive　drug　nanocarriers　are　widely　applied　for　cancer　treatment.　However,　the　mechanistic　details　of　drug　loading　and　drug　release　from　these　micelles　are　unknown.　Here,　we　reveal　the　mechanistic　details　of　micelle　formation,　drug　loading　and　drug　release　from　pH-responsive　polymeric　micelles　using　computer　simulations　and　experiments.　A　triblock　amphiphilic　copolymer,　methoxy-poly(ethylene　glycol)　2000-poly(2-(N,N-diethylamino)ethyl　methacrylate)-polycaprolactone　(mPEG-PDEA-PCL,　PDC),　was　used　to　load　paclitaxel　(PTX),　a　hydrophobic　anticancer　agent,　using　an　injection　method.　The　micelles　showed　strong　pH-responsive　behavior,　where　the　sizes　and　zeta　potentials　ranged　from　51　nm　and　19　mV　at　pH　4.5,　respectively,　to　22　nm　and　-5.5　mV　at　pH　8,　respectively,　with　greater　PTX　release　at　pH　6.5　than　that　at　pH　7.4.　Furthermore,　the　PTX-loaded　PDC　micelles　showed　higher　cytotoxicity　to　MCF-7　cells　at　pH　6.5　than　that　at　pH　7.4　due　to　differential　drug　release.　Molecular　dynamics　and　the　coarse-grained　dissipative　particle　dynamic　method　were　used　to　mimic　micelle　formation,　drug　loading　and　drug　release.　The　pH-responsive　segment,　PDEA,　transforms　to　its　protonated　form,　PDEAH(+),　in　an　acidic　environment.　PTX　and　PDC　form　micelles　based　on　hydrophobic　interactions,　where　PTX　inserts　into　the　hydrophobic　PDEA-PCL　core　in　a　neutral　environment.　An　acidic　transition　of　the　environment　leads　to　rapid　PTX　release　from　the　micelles　due　to　the　hydrophobic-hydrophilic　transition　of　PDEA　to　PDEAlr,　though　some　PTX　molecules　still　remain　in　the　PCL　core.　The　pH-responsive　PDC　micelles　are　suitable　for　triggered　drug　release　in　an　acidic　tumor　microenvironment.　The　PDC　micelle　is,　therefore,　a　promising　nanocarrier　of　anticancer　agents　for　cancer　treatment.　(C)　2017　Elsevier　B.V.　All　rights　reserved.