Effect of HIFU treatment on tumor targeting efficacy of docetaxel-loaded Pluronic nanoparticles

Abstract

Numerous studies have been performed to identify the microenvironment of solid tumors, which is responsible for the insufficient delivery of anticancer drugs to tumor cells due to the poorly organized vasculature and the increased interstitial fluid pressure. As a result, the extravasation of convection-dependent agents including NPs is severely limited. Therefore, we have demonstrated the feasibility of targeting an enhancement of docetaxel-loaded Pluronic nanoparticles (NPs) using high-intensity focused ultrasound (HIFU) as an external stimulus-induced clinical system in tumor tissue. The efficient extravasation of NPs into the interior cells in tumor tissue was induced by relatively low HIFU exposure without apparent acute tissue damage. The enhanced targeting of NPs with near-infrared fluorescence dye was observed in tumor-bearing mice with various HIFU exposures. As a result, the greatest accumulation of NPs at the tumor tissue was observed at an HIFU exposure of 20W/cm2. However, the tumor tissue above at 20W/cm2 appeared to be destroyed and the tumor targetability of NPs was significantly decreased owing to thermal ablation with necrosis, resulting in the destruction of the tumor tissue and the blood vessels. In particular, a cross-sectional view of the tumor tissue verified that the NPs migrated into the middle of the tumor tissue upon HIFU exposure. The preliminary results here demonstrate that HIFU exposure through non-thermal mechanisms can aid with the extravasation of NPs into the interior cells of tumors and increase the therapeutic effect in enhanced and targeted cancer therapy.