Coadministration of a tumor-penetrating peptide improves the therapeutic efficacy of paclitaxel in a novel air-grown lung cancer 3D spheroid model.

Three-dimensional (3 D) cell culture platforms are increasingly being used in cancer research and drug development since they mimic avascular tumors in vitro. In this study, we focused on the development of a novel air-grown multicellular spheroid (MCS) model to mimic in vivo tumors for understanding lung cancer biology and improvement in the evaluation of aerosol anticancer therapeutics. 3 D MCS were formed using A549 lung adenocarcinoma cells, comprising cellular heterogeneity with respect to different proliferative and metabolic gradients. The growth kinetics, morphology and 3 D structure of air-grown MCS were characterized by brightfield, fluorescent and scanning electron microscopy. MCS demonstrated a significant decrease in growth when the tumor-penetrating peptide iRGD and paclitaxel (PTX) were coadministered as compared with PTX alone. It was also found that when treated with both iRGD and PTX, A549 MCS exhibited an increase in apoptosis and decrease in clonogenic survival capacity in contrast to PTX treatment alone. This study demonstrated that coadministration of iRGD resulted in the improvement of the tumor penetration ability of PTX in an in vitro A549 3 D MCS model. In addition, this is the first time a high-throughput air-grown lung cancer tumor spheroid model has been developed and evaluated.