Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 14, Issue 8, Pages 2678-2688Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2018.06.012
Keywords
Nanocrystals; Combination treatment; Tumor microenvironment; Matrix metalloproteinases; Marimastat
Funding
- National Natural Science Foundation of China [81673377, 81473152, 81402869]
- Ministry of Science and Technology of China [2017ZX09101001]
- Fostering Plan of University Scientific and Technological Innovation Team and Key Members of the Outstanding Young Teacher of Jiangsu Qing Lan Project (2016)
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Treatment of metastatic cancer continues to be a huge challenge worldwide. Notably, drug nanocrystals (Ns) in nanosuspensions clearly belong to a type of nanoparticle. Therefore, a question arose as to whether these drug particles can also be applied as carriers for drug delivery. Here, we design a novel paclitaxel (PTX) nanocrystal stabilized with complexes of matrix metalloproteinase (MMP)-sensitive beta-casein/marimastat (MATT) for co-delivering MATT and PTX and combined therapy of metastatic breast cancer. The prepared Ns (200 nm) with a drug-loading of >50% were potent in treatment of metastatic cancer, which markedly inhibited MMP expression and activity and greatly blocked the lung metastasis and angiogenesis. In conclusion, employing protein-drug complexes as stabilizers, Ns with dual payloads are developed and are a promising strategy for co-delivery. Furthermore, the developed Ns can target the tumor microenvironment and cancer cells and, as a result, enable efficient treatment for breast metastatic cancer. (c) 2018 Elsevier Inc. All rights reserved.
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