A promising strategy for overcoming MDR in tumor by magnetic iron oxide nanoparticles co-loaded with daunorubicin and 5-bromotetrandrin

Figures & data

Figure 1 Physical characteristic of drug-loaded magnetic nanoparticles. (A) The nanoparticles under the transmission electron microscope. (B) Hydrodynamic particle size distribution of DNR/BrTet-loaded MNPs by Malvern Zetasizer Nano ZS90 (Malvern Instruments, Worcestershire, UK). (C) Magnetizaion as a function of field drug-loaded iron oxide nanoparticles by a vibration sample magnetometer. (D) Release of DNR and BrTet from MNPs under in-vitro conditions.

Abbreviations: DNR, daunorubicin; BrTet, 5-bromotetrandrin; MNP, magnetic nanoparticle.

Table 1 Drug loading of DNR and BrTet in MNPs (n = 3, mean ± standard deviation)

DNR (% w/w)		BrTet (% w/w)		Total drug loading (% w/w)
Added	Loaded	Added	Loaded
0.0	0.0	10.0	6.15 ± 0.65	6.15 ± 0.65
5.0	4.60 ± 0.39	5.0	3.65 ± 0.80	8.25 ± 1.13
10.0	7.62 ± 0.47	0.0	0.0	7.62 ± 0.47

Abbreviations: DNR, daunorubicin; BrTet, 5-bromotetrandrin; MNP, magnetic nanoparticle.

Table 2 Effect of MNPs and BrTet on K562/A02 cells for 48 hours (n = 3, mean ± standard deviation)

MNPs		BrTet
Concentration (μg/mL)	Relative growth rate (%)	Concentration (μg/mL)	Relative growth rate (%)
6.25	97.12 ± 1.31	0.1	103.46 ± 2.09
12.5	89.06 ± 0.36	0.5	105.02 ± 2.78
25	84.45 ± 1.24	1	102.95 ± 2.54
50	85.87 ± 4.50	2	91.87 ± 1.98a
100	81.79 ± 1.91b	5	14.02 ± 2.04

Notes:

a Relative growth rate was more than 90% when BrTet was less than 2 μg/mL.

b Relative growth rate was more than 80% when MNPs alone was less than 100 μg/mL.

Abbreviations: DNR, daunorubicin; BrTet, 5-bromotetrandrin; MNPs, magnetic nanoparticles.

Figure 2 Cytotoxicity effects on K562/A02 cells for 48 hours. (A) DNR with or without MNPs. (B) Co-administration of DNR and BrTet with or without MNPs.

Abbreviations: DNR, daunorubicin; BrTet, 5-bromotetrandrin; MNP, magnetic nanoparticle; W, weight.

Figure 3 Subcellular distribution of DNR in K562/A02 cells treated with DNR alone, DNR-MNPs, DNR/BrTet, and DNR/BrTet-MNPs under fluorescence microscope.

Abbreviations: DNR, daunorubicin; BrTet, 5-bromotetrandrin; MNP, magnetic nanoparticle.

Figure 4 Function of P-gp in K562/A02 cells. (A) Intracellular fluorescence intensity (FI) associated with R123 in treated cells: (a) control; (b) DNR; (c) BrTet; (d) DNR/ BrTet; (e) DNR-MNPs; (f) BrTet-MNPs; (g) DNR/BrTet-MNPs; (h) MNPs. (B) Relative R123 accumulation in K562/A02 cells. Data are presented as means ± standard deviation (n = 3) and analyzed using one-way analysis of variance.

Note: *P < 0.05, when compared with control group.

Abbreviations: BrTet, 5-bromotetrandrin; DNR, daunorubicin; FITC-H, heavy chain fluorescein isothiocyanate; MNP, magnetic nanoparticle; P-gp, P-glycoprotein; R123, rhodamine 123; RT-PCR, reverse transcriptase polymerase chain reaction.

Figure 5 Transcription of mdr1 and expressions of P-gp in K562/A02 cells. (A) Transcription of mdr1 mRNA by RT-PCR; (B) expression of P-gp by western blotting assay.

Note: *P < 0.05, when compared with control group.

Abbreviations: BrTet, 5-bromotetrandrin; DNR, daunorubicin; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; MNP, magnetic nanoparticle; P-gp, P-glycoprotein; RT-PCR, reverse transcriptase polymerase chain reaction.