Morphology and temporal interactions of silica particles influence the chemotherapeutic cancer cell death

Encapsulation of drugs into nanocarriers is proven to be highly promising approach in reducing drug toxicity and enhancing therapeutic efficacy. However, controlling the loading efficiency and capacity, and release of therapeutics at specific disease site has remained a key challenge, particularly for toxic chemotherapeutic drugs. This work explored the effect of treatment with empty silica nanoparticles (SNPs) and a chemotherapeutic drug either together (i.e. co-treatment) or in tandem (i.e. temporally spaced) with the SNPs on the cell ablation ability of the drug. The study also investigated whether the efficacy of the drug in response to these treatments was dependent on the morphology of particles. SNPs of four different morphologies (solid: SSNPs, dendritic: DSNPs, mesoporous: MSNPs, and rod: RSNP) were used, while cisplatin (CisPt) served as model chemotherapeutic. The efficacy of CisPt as a function of SNPs morphology and temporal treatment strategy was tested in HeLa cells. The results indicated that the morphology of particles as well as treatment strategy (i.e. co-incubation and post treatment) had an impact on not only the cell viability but also the cell death pathways, as evidenced by varying IC50 values and the flow cytometry analysis. Interestingly, co-treatment of SNPs with CisPt resulted in an across-the-board lower IC50 value compared to when the cells were first treated with SNPs for 24 h followed by CisPt treatment and even when CisPt was loaded into the particles for most of the SNPs. • Silica nanoparticles with various morphological and topographical features were synthesised through controlled sol-gel process. • Silica nanoparticle morphology and topology affects their interaction with cancer cells. • The work shows that it is not necessary to load the drug onto nanoparticles. Co-treatment of drug with particles can illicit enhanced therapeutic effect. • Co-treatment of silica nanoparticles can enhance the therapeutic activity of known chemotherapy drug, which was morphology dependent. • The cell death pathways are also affected by the treatment type and the morphology of the particles.