Abstract |
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 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, 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.
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Authors | Mengchi Sun, Hailun Jiang, Tian Liu, Xiao Tan, Qikun Jiang, Bingjun Sun, Yulong Zheng, Gang Wang, Yang Wang, Maosheng Cheng, Zhonggui He, Jin Sun |
Journal | Acta pharmaceutica Sinica. B
(Acta Pharm Sin B)
Vol. 12
Issue 2
Pg. 952-966
(Feb 2022)
ISSN: 2211-3835 [Print] Netherlands |
PMID | 35256957
(Publication Type: Journal Article)
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