Folic acid functionalised mesoporous core-shell silica nanoparticles loaded with carboplatin for lung cancer therapy

Abstract

The development of versatile mesoporous silica nanomaterials (MSNSs) with suitable textural properties is essential for the targeted and precise delivery of therapeutic drugs for the treatment of various diseases. Especially, loading of highly toxic platinum-based drugs is essential to reduce their toxic side effects. However, loading platinum-based drugs such as carboplatin in high quantity in porous materials is extremely challenging owing to the high hydrophobicity and lack of functional groups for interacting with surfaces of MSNS. In this study, we report a facile synthesis of core-shell MSNS by employing a unique combination of triple surfactants - pluronic P123, cetyltrimethylammonium bromide (CTAB) and fluorocarbon-4 (FC-4) for targeted delivery of the carboplatin for the treatment of lung cancer. The highly hydrophobic FC-4 plays a vital role in tuning the self-assembly and thereby controls the size, morphology, textural properties and uniform pore size distribution of the MSNS. The optimised MSNS with the size range of 300–320 nm, uniform size distribution, high surface area and ordered structure was successfully synthesised. A high drug loading of 26.7% was achieved on both bare and amine functionalised MSNS with a steady release of up to 60% and 37%, respectively, in PBS. The targeting efficiency of the folic acid functionalised particles was established by confocal microscopy, which showed higher cellular uptake of these particles in A549 cells. The high carboplatin loading and targeting ability resulted in high cytotoxicity from the folic acid functionalised and drug-loaded MSNS samples in PC9 cells compared to non-targeted and bare MSNS samples. Overall, this study proposes a new single-step synthesis of core-shell MSNS with high drug loading capacity that can be used to deliver drugs in treating different types of cancers.