A Dual Protective Drug Delivery System Based on Lipid Coated Core-Shell Mesoporous Silica for Efficient Delivery of Cabazitaxel to Prostate Cancer Cells

Abstract

Abstract Many advancements are happening in drug delivery to develop an excellent nanocarrier to deliver drugs to target sites bypassing clinical barriers, thereby improving cellular uptake. Lipid coating on mesoporous silica nanoparticles (MSNs) has significantly reduced the drawbacks of many MSNs and increased their compatibility. This study reports a dual protective acid stimuli-responsive lipid-coated core-shell mesoporous silica nanoparticle (CSMS) conjugated with cabazitaxel showing better drug release, cell uptake, and cytotoxicity, and suitability in the prostate cancer (PC-3) cell line. Initially, monodispersed CSMS were conjugated with cabazitaxel (CBZ) through a hydrazone linker (CBZ@Hy-CSMS), proving its appropriate use in designing a stimuli-responsive system. In the second part, CBZ-conjugated CSMS was coated with a lipid layer (L-CBZ@Hy-CSMS) by the liposome fusion method. The presented dual protective CSMS system showed a significant increase in drug delivery at pH 5.4 compared to 7.4, with a drastic decrease in premature drug release when exposed to pH 7.4. The lipid-coated CSMS showed excellent biocompatibility and better cellular uptake with enhanced cell cytotoxicity in PC-3 cancer cells as compared to the uncoated CSMS. CSMS with a lipid coating combined with a stimuli-responsive system could improve the therapeutic delivery and treatment difficulties in many other cell lines and diseases.