Characterization, in vitro evaluation and comparative study on the cellular internalization of mesoporous silica nanoparticle-supported lipid bilayers

Mesoporous silica nanoparticles (MSNs) and liposomes are inorganic and organic nano-vehicles that are widely used for drug delivery, respectively, however, their application as drug carriers have been limited by some of their inherent defects. In this study, mesoporous silica nanoparticle-supported lipid bilayers (LMSNs) were developed with doxorubicin (DOX) used as the model drug to be loaded. The different nanocarriers, including MSNs, amino-modified MSNs (MSNs-NH2 and MSNs-PEI), as well as LMSNs were systematically characterized and evaluated comparatively in terms of in vitro release, cytotoxicity towards MCF-7 cells, cellular internalization and cellular uptake mechanism. The results indicated that LMSNs had the more effective drug encapsulation, and various nanocarriers exhibited a pH-responsive release feature and the coverage of the lipid bilayer would retard the release of DOX to reach the sustained release effect. Facilitated by the lipid membrane affinity and improved stability supplied by PEGylated lipids, in comparison with both the bare and amino-modified MSNs, the internalization efficiency into cells and cytotoxicity of LMSNs was significantly enhanced. Further study results of the cellular uptake mechanism supported that LMSNs could be internalizated by cells through caveolae mediated endocytosis and macropinocytosis pathway, and these more efficient uptake pathway was probably the important cause for their higher cell internalization and delivery capacity. In summary, the LMSNs were the potent nanocarriers with promising properties and the findings will contribute to the rational design of multifunctional nano-drug carriers for efficient delivery and therapy.