Construction of calcium carbonate-liposome dual-film coated mesoporous silica as a delayed drug release system for antitumor therapy

As is well known to all, delivering drug precisely to the tumor site is beneficial to improve antitumor effect. In this study, we reported mesoporous silica nanoparticles (MSNs) coated with dual-film of calcium carbonate (CaCO3) and lipid bilayer (denoted as MSNs@CaCO3@liposomes) innovatively which achieve sustained drug release anchored at tumor microenvironment and enhanced biocompatibility. The pH-sensitive CaCO3 film acted as a guide to cap the pore channels of MSNs allowed pH-triggered drug release when transporting into cancer cells. Furthermore, MSNs@CaCO3 was capsuled by lipid bilayer to improve cellular uptake efficiency and biocompatibility in blood circulation. Morphology of nanoparticles was characterized by transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM) to confirm that double films were coated successfully. Doxorubicin hydrochloride (DOX) was efficaciously loaded into mesoporous pores as a model drug with a high drug loading content of 28%, forming DOX-loaded MSNs@CaCO3@liposomes (DOX/MSNs@CaCO3@liposomes). Non-specific protein adsorption and hemolysis test revealed enhanced biocompatibility. Drug release study in vitro showed DOX/MSNs@CaCO3@liposomes could delay to release DOX at pH 5.0 and avoid releasing at pH 7.4. In vitro and in vivo antitumor efficiency evaluation showed that DOX/MSNs@CaCO3@liposomes have a desirable inhibitory activity on tumor growth. Therefore, dual-film coated MSNs could be a good candidate for an antitumor drug delivery system.