High payload dual therapeutic-imaging nanocarriers for triggered tumor delivery

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. Homogeneous dual therapeutic-imaging nanocarriers containing a chemotherapeutic adjuvant, dexamethasone palmitate (DEX-P), and a signaling agent, ¹¹¹In, exhibit significant tumor uptake in single photon emission computed tomography images. High esterase activity in tumors, but not in human plasma, facilitates the esterolysis of the prodrug DEX-P resulting in the intra-tumoral release of DEX from DEX-P nanoparticles.