A　novel　metal–organic　particle　(MOP)　based　nanodrug　formed　by　mild　self-assembly　of　chemotherapeutic　drugs,　including　banoxantrone　and　doxorubicin,　through　Cu(II)-mediated　coordination　effects,　is　reported.　In　this　nanodrug,　Cu(II)　acts　as　a　bridge　to　join　AQ4N　and　DOX,　and　then,　self-assembly　of　[-AQ4N-Cu(II)-(DOX)2-Cu(II)-]n　complexes　forms　nanosized　MOPs　(referred　to　as　ADMOPs)　through　multiple　interactions　including　host–metal–guest　coordination,　hydrophobic　interactions,　π-stacking,　and　van　der　Waals　force.　The　ADMOPs　reported　here　have　several　important　features　over　conventional　drugs,　including　tumor　microenvironment　pH-sensitive　drug　release　that　can　be　tracked　by　＇turning　on＇　the　fluorescence　of　AQ4N　or　DOX　through　proton　competition　with　Cu(II)　to　break　the　coordination　bonds　and　much　deeper　penetration　into　solid　tumors　via　microvesicle-mediated　intercellular　transfer.　Most　strikingly,　the　ADMOPs　can　serve　as　stimuli-responsive　nanocarriers　to　efficiently　load　the　photosensitizer　phthalocyanine　due　to　their　inherent　highly　porous　characteristics.　Thus,　the　ADMOPs　significantly　enhance　the　chemotherapeutic　efficacy　by　＇on-demand＇　photodynamic　therapy,　which　further　induces　a　hypoxic　environment　that　enhances　the　reduction　of　AQ4N　to　systematically　increase　the　therapeutic　efficiency.　Taken　together,　the　designed　ADMOPs　composed　of　chemotherapeutic　drugs　may　serve　as　a　potential　programmable　controlled　synergistic　agent　for　cancer　therapy.　©　2018　The　Authors.　Published　by　WILEY-VCH　Verlag　GmbH　&　Co.　KGaA,　Weinheim