Structurally defined tandem-responsive nanoassemblies composed of dipeptide-based photosensitive derivatives and hypoxia-activated camptothecin prodrugs against primary and metastatic breast tumors  

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

机构地区：[1]Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [2]Key Laboratory of Structure-Based Drug Design and Discovery,Shenyang Pharmaceutical University,Ministry of Education,Shenyang 110016,China [3]School of Materials Science and Engineering,Ocean University of China,Qingdao 266100,China [4]College of Pharmacy,Guangxi University of Chinese Medicine,Nanning 530200,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第2期952-966,共15页药学学报（英文版）

基　　金：supported by National Natural Science Foundation of China,Nos.81773656 and U1608283;Liaoning Revitalization Talents Program,No.XLYC1808017;Key Projects of Technology Bureau in Shenyang,No.18400408;Key projects of Liaoning Province Department of Education,No.2017LZD03;China Postdoctoral Science Foundation(No.2020M680986)。

摘　　要：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.

关 键 词：Chemo-photodynamic Tandem-responsive Both-in-one co-nanoassembly Computational simulations CAMPTOTHECIN Pyropheophorbide Reactive oxygen species Breast tumor metastasis 

分 类 号：R91[医药卫生—药学]