Inhibitory effect of doxorubicin-loaded mesoporous silica nanoparticles on bladder cancer cells

Abstract

Objective To prepare mesoporous silica nanoparticles (MSN) loaded with doxorubicin (DOX) and to evaluate their physical properties, drug release, uptake by tumor cells, inhibition of cell proliferation and promotion of apoptosis. Methods DOX was loaded into the channels of MSN by infiltration to prepare mesoporous silica nanocomposites (MSN-DOX), whose morphology was then observed using transmission electron microscopy (TEM), and the size and surface charge of nanocomposites were measured with a nano particle size analyzer. Dialysis bag was applied to study drug release behavior of the nanocomposites under different pH conditions. Laser confocal microscopy was used to observe the uptake of MSN-DOX by bladder cancer cells. CCK-8 assay was carried out to detect the biocompatibility of MSN and the inhibitory effect of MSN-DOX on cell proliferation. Finally, the expression of apoptosis-related proteins was tested to analyze the effect of MSN-DOX on apoptosis. Results The prepared nanocomposites were spherical, uniform in size, in a size of 203.6±3.0 nm, with a surface charge of -8.1±4.7 mV. The DOX loading was 4.83%, and the encapsulation efficiency was 10.15%. In vitro studies showed that DOX was slowly released from the nanocomposites, and the release rate and total release amount were correlated with the environmental pH value. Lower pH value led to faster drug release rate and more total release amount. Cellular uptake experiments indicated the nanocomposites were efficiently ingested by tumor cells, thereby increasing the intracellular drug accumulation. In addition, MSN had good biocompatibility, and MSN-DOX significantly inhibited the proliferation and promoted the apoptosis of tumor cells, with increased expression levels of apoptosis-related proteins. Conclusion Our prepared MSN-DOX nanocomposites have good properties and stable structure, which can be efficiently ingested by bladder cancer cells, thus effectively inhibiting proliferation and promoting apoptosis of tumor cells.

Keywords

• nanomedicine
• bladder cancer
• mesoporous silica