Figure 4.
Illustration of potential benefits of using nanocarriers for ratio-metric delivery of synergistic drug combination for cancer treatment in clinical applications. A) Alteration of pharmacokinetics and biodistribution of ratiometric drug combination delivered by free solution. Upon intravenous (i.v.) administration, traditional free drug combination fails to maintain desired drug ratio (e.g. 2:1) before reaching the tumor (left). B) Nanocarrier delivered synergistic drug combination into cancer cells against multidrug-resistance in cancer. The nanoparticles accumulate in the tumor by the ERP effect or receptor-mediated extravasation, bind with tumor receptors, enter cancer cells via endocytosis, and release drugs within cancer cells. The released drugs translocate into nucleus where the site of drug action occurs in this case, to exert synergistic action, resulting in enhanced DNA double strand breaks. The figures were illustrated by Caitlin Swanberg.