Nano-hole induction by nanodiamond and nanoplatinum liquid, DPV576, reverses multidrug resistance in human myeloid leukemia (HL60/AR)

Abstract

Alia Ghoneum,1,2 Shivani Sharma,1,3 James Gimzewsk1,3 1Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, 2Department of Otalaryngology, Drew University of Medicine and Science, Los Angeles, 3California Nanosystems Institute (CNSI) at University of California, Los Angeles, Los Angeles, CA, USA Abstract: Recently nanoparticles have been extensively studied and have proven to be a promising candidate for cancer treatment and diagnosis. In the current study, we examined the chemo-sensitizing activity of a mixture of nanodiamond (ND) and nanoplatinum (NP) solution known as DPV576, against multidrug-resistant (MDR) human myeloid leukemia (HL60/AR) and MDR-sensitive cells (HL60). Cancer cells were cultured with different concentrations of daunorubicin (DNR) (1 × 10-9–1 × 10-6 M) in the presence of selected concentrations of DPV576 (2.5%–10% v/v). Cancer cell survival was determined by MTT assay, drug accumulation by flow cytometry and confocal laser scanning microscopy (CLSM), and holes and structural changes by atomic force microscopy (AFM). Co-treatment of HL60/AR cells with DNR plus DPV576 resulted in the reduction of the IC50 to 1/4th. This was associated with increased incidences of holes inside the cells as compared with control untreated cells. On the other hand, HL60 cells did not show changes in their drug accumulation post-treatment with DPV576 and DNR. We conclude that DPV576 is an effective chemo-sensitizer as indicated by the reversal of HL60/AR cells to DNR and may represent a potential novel adjuvant for the treatment of chemo-resistant human myeloid leukemia. Keywords: nanodiamond, nanoplatinum, daunorubicin, flow cytometry, AFM