Substantial progress in the use of chemo-photodynamic nano-drug delivery systems(nano-DDS)for the treatment of the malignant breast cancer has been achieved.The inability to customize pre-cise nanostructures,however,has limited the therapeutic efficacy of the prepared nano-DDS to date.Here,we report a structurally defined tandem-responsive chemo-photosensitive co-nanoassembly to eliminate primary breast tumor and prevent lung metastasis.This both-in-one co-nanoassembly is prepared by assembling a biocompatible photosensitive derivative(pheophorbide-diphenylalanine peptide,PPA-DA)with a hypoxia-activated camptothecin(CPT)prodrug[(4-nitrophenyl)formate camptothecin,N-CPT].According to computational simulations,the co-assembly nanostructure is not the classical core-shell type,but consists of many small microphase regions.Upon exposure to a 660 nm laser,PPA-DA induce high levels of ROS production to effectively achieve the apoptosis of normoxic cancer cells.Subsequently,the hypoxia-activated N-CPT and CPT spatially penetrate deep into the hypoxic region of the tumor and suppress hypoxia-induced tumor metastasis.Benefiting from the rational design of the chemo-photodynamic both-in-one nano-DDS,these nanomedicines exhibit a promising potential in the inhibition of difficult-to-treat breast tumor metastasis in patients with breast cancer.