Theranostic Nanoparticles for Imaging and Therapy and Cellular Response after Laser-induced Heating

Abstract

In our study, we use a new biocompatible and biodegradable polymer, which is termed poly(glycerol-co-malic-dodecanoate) (PGMD), for the synthesis of nanoparticles (NPs) and loading of Near-Infrared (NIR) dyes. IR820 was chosen for the purpose of imaging and hyperthermia (HT). One of the potential problems of hyperthermia (HT) is that HT can up-regulate hypoxia-inducible factor-1 (HIF-1) expression and enhance vascular endothelial growth factor (VEGF) secretion. We explored the cellular response after rapid, short-term and low thermal dose laser-IR820-PGMD NPs (laser/NP) induced-heating, and compared it to slow, long-term and high thermal dose heating using a cell incubator. The cytotoxicity of NPs after laser/NP HT resulted in higher cell killing compared to incubator HT. Reactive oxygen species (ROS), HIF-1, and VEGF level were highly elevated under incubator HT, but remained at the baseline level under the laser/NP HT. In vitro cell imaging and in vivo healthy mice imaging showed that IR820-PGMD NPs can be used for optical imaging. In conclusion, IR820-PGMD NPs were developed and used for both imaging and therapy purposes. Rapid and short-term laser/NP HT, with a low thermal dose, does not up-regulate HIF-1 and VEGF expression, whereas slow and long-term incubator HT, with a high thermal dose, enhances the expression of both transcription factors.