Journal
DRUG DELIVERY
Volume 26, Issue 1, Pages 1027-1038Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/10717544.2019.1676843
Keywords
Cell-penetrating peptide; cleavable peptide; curcumin; enzyme-responsive nanoparticle; targeting drug delivery
Categories
Funding
- National Natural Science Foundation of China [21376223]
- Zhejiang Provincial Natural Science Foundation of China [LY19B060012]
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The limitations of anticancer drugs, including poor tumor targeting and weak uptake efficiency, are important factors affecting tumor therapy. According to characteristics of the tumor microenvironment, in this study, we aimed to synthesize matrix metalloproteinase (MMP)-responsive curcumin (Cur)-loaded nanoparticles (Cur-P-NPs) based on amphiphilic block copolymer (MePEG-peptide-PET-PCL) with MMP-cleavable peptide (GPLGIAGQ) and penetrating peptide (r9), modified to improve tumor targeting and cellular uptake. The average size of Cur-P-NPs was 176.9?nm, with a zeta potential of 8.1?mV, and they showed drug entrapment efficiency and a loading capacity of 87.07% ? 0.63% and 7.44% ? 0.16%, respectively. Furthermore, Cur release from Cur-P-NPs was sustained for 144?h at pH 7.4, and the release rate was accelerated under enzyme reaction condition. The MTT assay demonstrated that free P-NPs had favorable biosafety, and the anti-proliferative activity of Cur-P-NPs was positively correlated with Cur concentration in MCF-7 cells. Additionally, the results of cellular uptake, in vivo pharmacokinetics, and biodistribution showed that Cur-P-NPs had a good effect on cellular uptake and tumor targeting, resulting in the best bioavailability in tumor therapy. Therefore, Cur-P-NPs, as a promising drug delivery system, might lead to a new and efficient route for targeted therapy in clinical practice.
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