Affiliation:
1. Cixi Institute of Biomedical Engineering International Cooperation Base of Biomedical Materials Technology and Application CAS Key Laboratory of Magnetic Materials and Devices Zhejiang Engineering Research Center for Biomedical Materials Ningbo Institute of Materials Technology and Engineering Chinese Academy of Sciences 315201 Ningbo P. R. China
2. University of Chinese Academy of Sciences 100049 Beijing P. R. China
Abstract
AbstractTriple‐negative breast cancer (TNBC) has the worst prognosis among all breast cancer subtypes due to lack of specific target sites and effective treatments. Herein, a transformable prodrug (DOX‐P18) based on neuropeptide Y analogue with tumor microenvironment responsiveness is developed for TNBC treatment. The prodrug DOX‐P18 can achieve reversible morphological transformation between monomers and nanoparticles through the manipulation of protonation degree in different environments. It can self‐assemble into nanoparticles to enhance the circulation stability and drug delivery efficiency in the physiological environment while transforming from nanoparticles to monomers and being endocytosed into the breast cancer cells in the acidic tumor microenvironment. Further, the DOX‐P18 can precisely be enriched in the mitochondria, and efficiently activated by matrix metalloproteinases. Then, the cytotoxic fragment (DOX‐P3) can subsequently be diffused into the nucleus, generating a sustained cell toxicity effect. In the meanwhile, the hydrolysate residue P15 can assemble into nanofibers to construct nest‐like barriers for the metastasis inhibition of cancer cells. After intravenous injection, the transformable prodrug DOX‐P18 demonstrated superior tumor growth and metastasis suppression with much better biocompatibility and improved biodistribution compared to free DOX. As a novel tumor microenvironment‐responsive transformable prodrug with diversified biological functions, DOX‐P18 shows great potential in smart chemotherapeutics discovery for TBNC.
Funder
National Natural Science Foundation of China
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献