Targeting intracellular MMPs efficiently inhibits tumor metastasis and angiogenesis

Theranostics
Yaqi LvLifang Yin

Abstract

Treatment for metastatic cancer is a great challenge throughout the world. Commonly, directed inhibition of extracellular matrix metalloproteinases (MMPs) secreted by cancer cells can reduce metastasis. Here, a novel nanoplatform (HPMC NPs) assembled from hyaluronic acid (HA)-paclitaxel (PTX) prodrug and marimastat (MATT)/β-casein (CN) complexes was established to cure a 4T1 metastatic cancer model via targeting CD44 and intracellular, rather than extracellular, MMPs. Methods: HPMC NPs were prepared by assembling the complexes and prodrug under ultrasonic treatment, which the interaction between them was evaluated by förster resonance energy transfer, circular dichroism and fluorescence spectra. The developed nanoplatform was characterized via dynamic light scattering and transmission electron microscopy, and was evaluated in terms of MMP-sensitive release and stability. Subsequently, the cellular uptake, trafficking, and in vitro invasion were studied by flow cytometry, confocal laser microscopy and transwell assay. MMP expression and activity was determined by western blotting and gelatin zymography. Finally, the studies of biodistribution and antitumor efficacy in vivo were performed in a mouse 4T1 tumor breast model, follow...Continue Reading

Citations

Jun 30, 2019·Bioengineering & Translational Medicine·Yaqi LyuLifang Yin
Aug 18, 2020·Cancer Control : Journal of the Moffitt Cancer Center·Yu-Shui MaDa Fu
Aug 10, 2019·Scientific Reports·Debasmita DuttaMita Chatterjee Debnath
Jun 25, 2020·Journal of Experimental & Clinical Cancer Research : CR·Jun-Jie ChenJian-Wei Zhou
Jan 7, 2021·The FEBS Journal·Wesam BassiouniRichard Schulz
Oct 31, 2020·International Journal of Molecular Sciences·Alexandru TirpeIoana Berindan-Neagoe
Feb 16, 2021·Frontiers in Pharmacology·Qinghui ZhengXuli Meng
Feb 25, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Mohsin Ahmad GhauriYanmin Zhang
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Maywan HarionoHabibah Wahab
Jun 9, 2021·Nutrition and Cancer·Andrés Cardona-MendozaSandra J Perdomo
Jun 21, 2021·Cancer Treatment and Research Communications·Fares Hezam Al-OstootShaukath Ara Khanum

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Methods Mentioned

BETA
dynamic laser scattering
confocal microscopy
protein assay
flow cytometry
FRET
zymography

Software Mentioned

Gel pro

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