Structurally defined tandem-responsive nanoassemblies composed of dipeptide-based photosensitive derivatives and hypoxia-activated camptothecin prodrugs against primary and metastatic breast tumors.
10.1016/j.apsb.2021.08.008
- Author:
Mengchi SUN
1
;
Hailun JIANG
2
;
Tian LIU
1
;
Xiao TAN
1
;
Qikun JIANG
1
;
Bingjun SUN
2
;
Yulong ZHENG
3
;
Gang WANG
4
;
Yang WANG
4
;
Maosheng CHENG
2
;
Zhonggui HE
1
;
Jin SUN
1
Author Information
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.
- Publication Type:Journal Article
- Keywords:
Both-in-one co-nanoassembly;
Breast tumor metastasis;
Camptothecin;
Chemo-photodynamic;
Computational simulations;
Pyropheophorbide;
Reactive oxygen species;
Tandem-responsive
- From:
Acta Pharmaceutica Sinica B
2022;12(2):952-966
- CountryChina
- Language:English
-
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.
