In vitro research of stimuli-responsive mesoporous silica nanoparticles loaded with anthraquinone-modified 4S on triple-negative breast cancer

Objective: To investigate whether stimuli-responsive mesoporous silica nanoparticles (MSNs-SSHA) as a drug delivery system can improve the targeting and bioavailability of anthraquinone-modified 4S to triple-negative breast cancer (TNBC) cells, while minimizing the toxicity to normal cells. Methods: Functionalized nanoparticles MSNs-SS-HA were prepared by post-modification method, and characterized through transmission electron microscopy, Malvern particle size analyzer, Fourier transform infrared spectroscopy, and elemental analysis. In vitro dialysis experiments were performed to detect the release behavior of MSNs@4S and MSNs-SSHA@4S in different concentrations of glutathione buffer solutions. The inhibitory activity of free 4S and drugloaded nanoparticles on TNBC cells MDA-MB231, breast cancer cells MCF-7 and normal breast cancer cells MCF-10A was determined by MTT assay. Laser confocal microscopy was used to observe the uptake of anthraquinone-modified 4S and drug-loaded nanoparticles in different cells. Results: Functionalized drug-loaded nanoparticles MSNs-SS-HA@4S were successfully prepared, with a drug loading capacity and encapsulation efficiency of (17.43±1.2)% and (90.56±1.1)%, respectively. The drug-loaded nanoparticles MSNs-SS-HA@4S exhibit reduction-responsive properties and slow-release drug effects. At the same concentration, the toxicity of MSNsSS-HA@4S to MDA-MB231 cells was higher than that to MCF-10A cells, but the antitumor activity against MCF-7 cells was weaker (P＜0.05). In vitro cellular uptake experiments showed that MSNs-SS-HA@4S was able to target MDA-MB231, a TNBC cell with high expression of CD44, and might enter the cells through CD44 receptor-mediated endocytosis, revealing the potential of MSNs-SS-HA@4S for tumor-targeted therapy. Conclusion: MSNs-SS-HA@4S improves the efficacy of anthraquinone modified-4S in potentiation and toxicity reduction, providing new ideas for targeted therapy of TNBC.