In vivo translation of a dual-stimuli-responsive drug carrier based on mesoporous silica nanoparticles for the co-delivery of camptothecin and 5-fluorouracil

Abstract

With the advent of nanotechnology, combined drug therapies employing dual-drug delivery provide an efficient way to overcome the drawbacks of conventional chemotherapy, such as lack of specificity, multidrug resistance and low aqueous solubility. Herein, a dual-drug delivery system based on mesoporous silica nanoparticles (MSNs) was developed to target tumours with the dual-responsive co-delivery of two anticancer drugs, camptothecin (CPT) and 5-fluorouracil (5-FU), in a sequential manner. The mesopores were loaded with CPT, and subsequently, a pegylated-biotin polymer was used to coat them. The disulphide link and acid group present in the polymer contribute to the stimuli-triggered release of the drugs. Since cancer cells need biotin to continue proliferating, it functions as a targeting ligand. Mathematical modelling studies revealed that the drug-release kinetics followed a diffusion mechanism for both the hydrophobic and hydrophilic drugs. Beyond in vitro release and cytotoxicity assays, extensive in vivo biological evaluations, including liver function markers, serum biochemistry and histopathological examinations, demonstrated pronounced tumour suppression with reduced hepatic toxicity. The nanocarrier downregulated key tumour biomarkers, effectively lowered serum transaminases and restored normal liver architecture. Collectively, these findings affirm the translational potential of this smart dual-drug delivery platform for cancer therapy.