Nano-gold micelles loaded Dox and Elacridar for reversing drug resistance of breast cancer

Abstract

The aim of this study was to provide a new effective carrier for rescuing the sensitivity of drug-resistant in breast cancer cells. Nano-gold micelles loaded with Dox and Elacridar (FP-ssD@A-E) were chemically synthesised. With the increase in the amount of Dox and Elacridar, the encapsulation rate of FP-ssD@A-E gradually increased, and the drug loading rate gradually decreased. FP-ss@A-E had a sustained-release effect. Dox, Elacridar, FP-ss@AuNPs, and FP-ssD@A-E significantly improved cell apoptosis, in which, FP-ssD@A-E was the most significant. FP-ssD@A-E significantly decreased the cell viability and improved the Dox uptake. The levels of VEGFR-1, P-gp, IL-6, and i-NOS were significantly decreased after Dox, Dox + Elacridar, FP-ss@AuNPs, and FP-ssD@A-E treatment. It was worth noting that FP-ssD@A-E had the most significant effects. The prepared FP-ssD@A-E micelles, which were spherical in shape, uniform in particle size distribution, and had good drug loading performance and encapsulation efficiency.

Keywords: breast cancer; doxorubicin; drug loaded hybrid micelles; elacridar; gold nanoparticles.

Scheme 1

The preparation of P(tBMA)‐P(MMA‐SS‐DOX)

FIGURE 1

Chemical structure characterisation of dual drug‐loaded nanomicelles. (a) ¹H NMR of MMA‐SS‐NH2, DOX, MMA‐SS‐DOX, and P(tBMA)‐P(MMA‐SS‐Dox). (b) FTIR spectra of DOX, AuNPs, Elacridar, FP‐ss@AuNPs, and FP‐ssD@A‐E. (c) The light absorption values of DOX, AuNPs, Elacridar, FP‐ss@AuNPs, and FP‐ssD@A‐E under different wavelength conditions. (d) The XRD spectra.

FIGURE 2

Morphology analysis of dual drug‐loaded nanomicelles. (a) The transmission electron microscope (TEM) test. (b) The dynamic laser light scattering (DLS) assay. (c) The zeta potential of AuNPs, FP‐ss@AuNPs, and FP‐ssD@A‐E.

FIGURE 3

Drug release of dual drug‐loaded nanomicelles. (a) The regression equation of the standard curve of DOX was y = 0.65x + 0.00627, and the regression equation of the standard curve of Elacridar was y = 349721x − 97.96. (b) With the increase in the amount of Elacridar and DOX, the encapsulation rate of FP‐ssD@A‐E gradually increased, and the drug loading rate gradually decreased. (c) FP‐ss@A‐E had a sustained‐release effect.

FIGURE 4

Cell cytotoxicity in vitro. (a) FP‐ss@AuNPs nanoparticles were non‐cytotoxic. (b−e) Free Dox, Elacridar, and FP‐ssD@A‐E have dose‐dependent toxicity to HBL‐100, MCF‐7, and MCF‐7/MDR cells. Compared with HBL‐100 group, *p < 0.05, **p < 0.01, ***p < 0.001, Compared with MCF‐7 group, #p < 0.05, ##p < 0.01. (f−h) The differences in cell proliferation of HBL‐100, MCF‐7, and MCF‐7/MDR in each group at 2, 8, 24, and 48 h. Compared with free Dox group, *p< 0.05, **p < 0.01, ***p < 0.001.

FIGURE 5

FP‐ssD@A‐E improved cell apoptosis

FIGURE 6

FP‐ssD@A‐E significantly improved the Dox uptake.

FIGURE 7

FP‐ss@AuNPs decreased cytokine level