TY - JOUR A1 - Onafuye, Hannah A1 - Pieper, Sebastian A1 - Mulac, Dennis A1 - Jr., Jindrich Cinatl A1 - Wass, Mark N. A1 - Langer, Klaus A1 - Michaelis, Martin T1 - Doxorubicin-loaded human serum albumin nanoparticles overcome transporter-mediated drug resistance in drug-adapted cancer cells JF - Beilstein Journal of Nanotechnology PY - 2019/// VL - 10 SP - 1707 EP - 1715 SN - 2190-4286 DO - 10.3762/bjnano.10.166 PB - Beilstein-Institut JA - Beilstein J. Nanotechnol. UR - https://doi.org/10.3762/bjnano.10.166 KW - ABCB1 KW - cancer KW - doxorubicin KW - drug resistance KW - human serum albumin KW - nanoparticles KW - transporter N2 - 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. ER -