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.

Mengchi Sun;Hailun Jiang;Tian Liu;Xiao Tan;Qikun Jiang;Bingjun Sun;Yulong Zheng;Gang Wang;Yang Wang;Maosheng Cheng;Zhonggui He;Jin Sun

Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China;Key Laboratory of Structure-Based Drug Design and Discovery,Shenyang Pharmaceutical University,Ministry of Education,Shenyang 110016,China;School of Materials Science and Engineering,Ocean University of China,Qingdao 266100,China;College of Pharmacy,Guangxi University of Chinese Medicine,Nanning 530200,China

药学学报（英文版）

[1]Mengchi Sun;Hailun Jiang;Tian Liu;Xiao Tan;Qikun Jiang;Bingjun Sun;Yulong Zheng;Gang Wang;Yang Wang;Maosheng Cheng;Zhonggui He;Jin Sun-.Structurally defined tandem-responsive nanoassemblies composed of dipeptide-based photosensitive derivatives and hypoxia-activated camptothecin prodrugs against primary and metastatic breast tumors)[J].药学学报（英文版）,2022(02):952-966

nanoassemblies,nanoassembly,pheophorbide,diphenylalanine

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