Beyond the imaging: limitations of cellular uptake study in the evaluation of nanoparticles.

Journal of Controlled Release : Official Journal of the Controlled Release Society
Emily Gullotti, Yoon Yeo

Abstract

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) conjugated to a cell-penetrating peptide, TAT, was used to increase intracellular delivery of paclitaxel (PTX) to multi-drug resistant (MDR) cells. Efficient cellular uptake of the TAT-conjugated PLGA NPs was observed; however, it did not translate to increased killing of MDR cells. An investigation of drug release kinetics in phosphate-buffered saline containing Tween 80 led us to suspect that a significant fraction of the loaded PTX was released before efficient cellular uptake could occur. These results indicate that the increased cellular uptake of NPs does not always mean an enhanced drug effect and that it is critical to control both the location of NPs and the drug release from NPs together. Based on this study, we propose that two prevalent practices in NP research be reconsidered: first, the utility of a new NP system should be tested beyond the imaging level. Second, NP release kinetics should be monitored in a medium that can reflect the complexity of biological environment rather than a simple buffered saline.

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Citations

Nov 12, 2013·Archives of Pharmacal Research·Karen C Liu, Yoon Yeo
Sep 13, 2013·Therapeutic Delivery·Kyrillus S Shohdy, Ahmad Samir Alfaar
Mar 7, 2013·Molecular Pharmaceutics·Eun Jung ChoYoon Yeo
Jan 7, 2016·Bioconjugate Chemistry·Dalit Landesman-Milo, Dan Peer
Jan 10, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·C ConteF Quaglia
May 7, 2013·Current Opinion in Solid State & Materials Science·Bo Sun, Yoon Yeo
Jan 21, 2014·Molecular Pharmaceutics·Pengcheng ZhangHonggang Cui
Oct 17, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Rebecca L CookRachael W Sirianni
Mar 4, 2015·Nanoscale·Shazid Md SharkerSung Young Park
May 31, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Bo SunYoon Yeo
Jul 19, 2016·Expert Opinion on Drug Delivery·Noura H Abd Ellah, Sara A Abouelmagd
Aug 28, 2021·Journal of Biomedical Nanotechnology·Thaís Dolzany de OliveiraDayane Batista Tada

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