Near-infrared imaging loaded polymeric nanoparticles: In vitro and In vivo studies

摘要

Introduction: Recent research has focused on developing new biomaterials for delivery of imaging agents and drugs. In our study, we report a new biocompatible and biodegradable polymer, termed poly(glycerol-co-malic-dodecanoate) (PGMD), which was then used for synthesis of nanoparticles (NPs) and loading of NIR dyes. Methods: The PGMD polymer was synthesized via thermal condensation method and was characterized by FTIR. The NPs were synthesized via o/w single emulsion technique. IR820 was chosen as the NIR dye. The loading efficiency of IR820 in PGMD NPs was measured by spectrophotometer. The release of IR820 was estimated with a spectrofluorometer in different pH phosphate buffered saline. The cytotoxicity of NPs was estimated through a Sulforhodamine B colorimetric assay. A biodistribution and pharmacokinetics study of the NPs versus free IR820 was performed in a murine model (n=12) after i.v. injection. Plasma samples were collected at time points 15-30-60 minutes and 24 hours. Organ samples were also collected and measured at the 24-hour time point. Results and Discussion: Void PGMD NPs and IR820-PGMD NPs had mean sizes around 90 nm and 110 ran, respectively. FTIR showed that polyester bonds were forming in the PGMD polymer. The release of IR820 was increased in acidic buffer (pH=5.0) as compared to neutral buffer (pH=7.4), indicating that the release of IR820 is controllable. Cellular uptake studies showed comparable fluorescence of IR820-PGMD NPs to free IR820 (5 μM) after 24-hour exposure. IR820-PGMD NPs induced significant cancer cell killing after laser exposure due to the photothermal effect of the dye. In vivo studies showed that the IR820 in NPs formulation has a longer plasma half-life than free IR820, providing longer imaging collection times for cancer diagnostics, and potentially widening the window for hyperthermia applications. Conclusion: We expect that ease of synthesis and good biocompatibility make PGMD a good candidate for numerous imaging agent and drug delivery applications. The IR820-PGMD NPs have the ability to be used for both imaging and hyperthermia purposes.