Multifunctional Covalent Nanoconjugate for Near-Infrared Imaging and Hyperthermia

The design of novel multifunctional probes in the nanorange has the potential to improve cancer management by combining diagnostic and therapeutic capabilities. Nearinfrared (NIR) dyes, such as IR820, are good candidates for use as theranostic probes based on their optical and thermal generation properties. We prepared a covalent nanoconjugate of IR820 and PEG-diamine (IRPDcov), studied its optical imaging and hyperthermia applications in cancer cells, and performed biodistribution and pharmacokinetic studies in mice. The nanoconjugate particles had 150-nm diameter per SEM, zeta potential -0.4±0.3 mV, and their fluorescence stability was significantly higher compared to free dye after 72 hours. Cancer cells incubated with IRPDcov versus the same content of free IR820 showed an increased fluorescent signal as well as significantly decreased cell viability after laser exposure. In mice, IRPDcov had significantly longer (p<;0.05) distribution half-life, elimination half-life, and area-under-the-curve exposure compared to IR820. IRPDcov also showed reduced accumulation in the kidneys and significantly lower (p<;0.05) accumulation in the lungs compared to IR820. Some potential advantages of IRPDcov may include passive targeting of tumor tissue through the enhanced permeability and retention effect, prolonged circulation times resulting in increased windows for combined diagnosis and therapy, and further opportunities for functionalization and targeting.