PBPK modeling-based optimization of site-specific chemo-photodynamic therapy with far-red light-activatable paclitaxel prodrug

Photodynamic therapy (PDT) is a clinically approved therapeutic modality to treat certain types of cancers. However, incomplete ablation of tumor is a challenge. Visible and near IR-activatable prodrug, exhibiting the combined effects of PDT and local chemotherapy, showed better efficacy than PDT alone, without systemic side effects. Site-specifically released chemotherapeutic drugs killed cancer cells surviving from rapid PDT damage via bystander effects. Recently, we developed such a paclitaxel (PTX) prodrug that targets folate receptors. The goals of this study were to determine the optimal treatment conditions, based on modeling, for maximum antitumor efficacy in terms of drug-light interval (DLI), and to investigate the impact of rapid PDT effects on the pharmacokinetic (PK) profiles of the released PTX.