High Payload Dual Therapeutic‐Imaging Nanocarriers for Triggered Tumor Delivery

Abstract The in vitro and in vivo characterization of an optimized formulation of nanoparticles (NPs) loaded with a high content of dexamethasone palmitate (DEX‐P), a chemotherapeutic adjuvant that decreases interstitial fluid pressure in tumors, and ¹¹¹In, a signaling agent, is described. These NPs are uniform in size and composition. Single photon emission computed tomography imaging demonstrates significant tumor uptake of ¹¹¹In‐labeled DEX‐P NPs in tumor‐bearing mice. As with many nanoparticle‐based drug delivery systems, significant liver accumulation is observed. Assessment of liver histology and blood tests show no apparent hepatic or renal toxicity of the DEX‐P NPs. Conversion of DEX‐P to DEX occurs when DEX‐P NPs are incubated with mouse plasma, human tumor homogenate and ascites from tumor bearing mice, but not with human plasma. This conversion is slower in plasma from Es1^e(‐/‐)/SCID mice, a potential alternative animal model that better mimics humans; however, plasma from these mice are not completely devoid of esterase activity. The difference between blood and tumor esterase activity in humans facilitates the delivery of DEX‐P NPs to tumors and the release of dexamethasone by an esterase trigger.