Nanovesicle-mediated delivery of anticancer agents effectively induced cell death and regressed intrahepatic tumors in athymic mice

Laboratory Investigation; a Journal of Technical Methods and Pathology
Joseph GeorgeTushar Patel

Abstract

Hepatocellular carcinoma is highly resistant to chemotherapy. Here we evaluated the use and efficacy of milk-derived nanovesicles (MNV) as an approach to improve delivery of anticancer agents into HCC cells and intrahepatic tumors. We developed a protocol for isolation of MNVs from skim milk using ultracentrifugation, and characterized using nanoparticle tracking analysis (NTA) and electron microscopy. MNVs were loaded with doxorubicin (dox-MNV) or miR221 antisense oligonucleotides (anti-miR221-MNV), and further evaluated using spectrophotometry, NTA, and zeta potential measurements. HepG2, Hep3B, and PLC/PRF/5 HCC cells in culture were treated with dox-MNV and anti-miR221-MNV and evaluated with drug delivery and anticancer activity. The efficacy of dox-MNV and anti-miR221-MNV to arrest tumor growth in vivo was assessed on intrahepatic tumors induced in nude mice. Cellular uptake studies showed plain and dox-MNV attained saturation within 4 h of treatment. Cytotoxicity studies on HepG2, Hep3B, and PLC/PRF/5 HCC cells with dox-MNV at 1 µM resulted in 20% cell death at 24 h, 50% at 48 h, and 80% at 72 h. HepG2 cells treated with dox-MNV and anti-miR221-MNV exhibited nuclear disintegration, and apoptosis within 24 h. Combination t...Continue Reading

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Citations

Dec 27, 2019·Journal of Applied Toxicology : JAT·Akiko MatsudaTushar Patel
Mar 1, 2019·International Journal of Molecular Sciences·Safia NazJinghua Chen
Jan 27, 2021·Clinical and Experimental Pharmacology & Physiology·Yuehai PanFan Chen
Mar 23, 2021·Advanced Drug Delivery Reviews·Michaela Schulz-Siegmund, Achim Aigner
May 26, 2021·Biomaterials Science·Mohammed Mehadi Hassan ChowdhuryMd Nurunnabi
Jun 29, 2021·Frontiers in Bioengineering and Biotechnology·Julia DriscollTushar Patel
Jul 17, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Mohamed Fawzi KabilIbrahim M El-Sherbiny
Apr 8, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Julia DriscollTushar Patel

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Methods Mentioned

BETA
transmission electron microscopy
antisense oligonucleotide
dot-blot
fluorescence microscopy
confocal microscopy
electron microscopy

Software Mentioned

Image
zetasizer
Pro Plus

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