Combinatorial treatment using bevacizumab/pemetrexed loaded core-shell silica nanoparticles for non-small cell lung cancer

Abstract

ABSTRACTNon-small cell lung cancer (NSCLC) is a life-threatening cancer associated with a higher mortality rate. Despite promising results shown by combination therapies, there remains a need for efficient drug delivery materials capable of combining various drugs, imaging agents, and targeting agents to enhance treatment efficacy. In this study, we present the synthesis of novel core-shell hollow mesoporous silica nanoparticles (@MSN) with bimodal porosity and a large surface area (694 m2/g) to facilitate targeted drug delivery for NSCLC treatment. The hollow core-shell structure enables the loading of a substantial quantity of the pemetrexed drug, up to 839 µg/mg, with a sustained release of 20% within 48 h. The MSN is surface functionalised with amino and carboxyl groups to accommodate an imaging agent and facilitate the attachment of the targeting drug bevacizumab. These particles exhibit rapid uptake by both A549 and PC-9 cells. Moreover, the targeting by bevacizumab leads to higher cytotoxicity within 48 h and induces apoptosis more effectively than the non-functionalised samples. As a versatile drug delivery platform, the hollow core-shell MSN demonstrated in this study holds great potential for various drug delivery applications.

Keywords

• Non-small cell lung cancer (NSCLC)
• combinatorial treatment
• core-shell silica nanoparticles