Evaluation and live monitoring of pH-responsive HSA-ZnO nanoparticles using a lung-on-a-chip model

One of the key problems that have hindered the development and approval of anticancer nanoparticle drug delivery systems is the limited predictability of 2D cell culture and animal models. Here, we describe a biomimetic alveolus-epithelium-on-a-chip (AEOC) model with in-built sensors for monitoring and evaluating pH-responsive zinc oxide quantum dots (QDs)-loaded human serum albumin nanoparticles. This AEOC model closely represents the cancerous alveolus epithelium, which comprises lung cancer cells, as well as stromal cells, such as fibroblasts along with extracellular matrix (ECM) in the form of collagen. ZnO QDs were encapsulated in the HSA nanoparticles with a diameter of 60 nm. The physicochemical properties, quantum dots release, in vitro cytotoxicity, and cellular uptake of HSA-ZnO were evaluated. HSA-ZnO showed higher ZnO loading and encapsulation efficacy. TEER and pH sensors were used to monitor the cells over three days, and real-time data with and without nanoparticle treatment were obtained. Cell viability after treatment with 10 and 50 µg/mL of HSA-ZnO nanoparticles and confocal imaging data confirmed the significant internalization of the nanoparticles under co-culture cellular conditions in the AEOC model. Our designed organ-on-a-chip model has potentially expanded the capabilities of cell culture in biomimetic conditions, and therefore, can provide a low-cost alternative to expensive and tedious animal models for the evaluation of nanomedicines.