Doxorubicin-loaded human serum albumin nanoparticles overcome transporter-mediated drug resistance in drug-adapted cancer cells

Beilstein Journal of Nanotechnology. 2019;10(1):1707-1715 DOI 10.3762/bjnano.10.166

 

Journal Homepage

Journal Title: Beilstein Journal of Nanotechnology

ISSN: 2190-4286 (Online)

Publisher: Beilstein-Institut

LCC Subject Category: Technology: Chemical technology | Science: Physics

Country of publisher: Germany

Language of fulltext: English

Full-text formats available: PDF, HTML, XML

 

AUTHORS

Hannah Onafuye (Industrial Biotechnology Centre and School of Biosciences, University of Kent, Canterbury CT2 7NJ, United Kingdom)
Sebastian Pieper (Institute of Pharmaceutical Technology and Biopharmacy, University of Münster, Corrensstr. 48, 48149 Münster, Germany)
Dennis Mulac (Institute of Pharmaceutical Technology and Biopharmacy, University of Münster, Corrensstr. 48, 48149 Münster, Germany)
Jindrich Cinatl Jr. (Institute for Medical Virology, University Hospital, Goethe-University, Paul Ehrlich-Straße 40, 60596 Frankfurt am Main, Germany)
Mark N. Wass (Industrial Biotechnology Centre and School of Biosciences, University of Kent, Canterbury CT2 7NJ, United Kingdom)
Klaus Langer (Institute of Pharmaceutical Technology and Biopharmacy, University of Münster, Corrensstr. 48, 48149 Münster, Germany)
Martin Michaelis (Industrial Biotechnology Centre and School of Biosciences, University of Kent, Canterbury CT2 7NJ, United Kingdom)

EDITORIAL INFORMATION

Peer review

Editorial Board

Instructions for authors

Time From Submission to Publication: 23 weeks

 

Abstract | Full Text

Resistance to systemic drug therapy is a major reason for the failure of anticancer therapies. Here, we tested doxorubicin-loaded human serum albumin (HSA) nanoparticles in the neuroblastoma cell line UKF-NB-3 and its ABCB1-expressing sublines adapted to vincristine (UKF-NB-3rVCR1) and doxorubicin (UKF-NB-3rDOX20). Doxorubicin-loaded nanoparticles displayed increased anticancer activity in UKF-NB-3rVCR1 and UKF-NB-3rDOX20 cells relative to doxorubicin solution, but not in UKF-NB-3 cells. UKF-NB-3rVCR1 cells were re-sensitised by nanoparticle-encapsulated doxorubicin to the level of UKF-NB-3 cells. UKF-NB-3rDOX20 cells displayed a more pronounced resistance phenotype than UKF-NB-3rVCR1 cells and were not re-sensitised by doxorubicin-loaded nanoparticles to the level of parental cells. ABCB1 inhibition using zosuquidar resulted in similar effects like nanoparticle incorporation, indicating that doxorubicin-loaded nanoparticles successfully circumvent ABCB1-mediated drug efflux. The limited re-sensitisation of UKF-NB-3rDOX20 cells to doxorubicin by circumvention of ABCB1-mediated efflux is probably due to the presence of multiple doxorubicin resistance mechanisms. So far, ABCB1 inhibitors have failed in clinical trials probably because systemic ABCB1 inhibition results in a modified body distribution of its many substrates including drugs, xenobiotics, and other molecules. HSA nanoparticles may provide an alternative, more specific way to overcome transporter-mediated resistance.