Substantial progress in the use of chemo-photodynamic nano-drug delivery systems(nanoDDS) for the treatment of the malignant breast cancer has been achieved. The inability to customize precise nanostructures, however,...Substantial progress in the use of chemo-photodynamic nano-drug delivery systems(nanoDDS) for the treatment of the malignant breast cancer has been achieved. The inability to customize precise 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, PPADA) with a hypoxia-activated camptothecin(CPT) prodrug [(4-nitrophenyl) formate camptothecin, NCPT]. 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.展开更多
基金supported by National Natural Science Foundation of China,Nos.81773656 and U1608283Liaoning Revitalization Talents Program,No.XLYC1808017+2 种基金Key Projects of Technology Bureau in Shenyang,No.18400408Key projects of Liaoning Province Department of Education,No.2017LZD03China Postdoctoral Science Foundation(No.2020M680986)。
文摘Substantial progress in the use of chemo-photodynamic nano-drug delivery systems(nanoDDS) for the treatment of the malignant breast cancer has been achieved. The inability to customize precise 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, PPADA) with a hypoxia-activated camptothecin(CPT) prodrug [(4-nitrophenyl) formate camptothecin, NCPT]. 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.
