IR820 nanoconjugates for theranostic applications
Near-infrared dyes can be used as theranostic agents in cancer management based on their optical imaging and localized hyperthermia capabilities. However, their clinical translatability is limited by issues such as photobleaching, short circulation times, and non-specific biodistribution. We studied the applications of IR820 in optical imaging and hyperthermia, and we prepared nanoconjugate formulations to overcome some of the aforementioned limitations. Free IR820 can be used for optical imaging, with a strong signal still present 24 hours after i.v. injection, an elimination plasma half-life in the order of hours, and primary biodistribution to liver, lung, and kidneys. After 808-mn laser exposure, IR820 can also raise in vitro temperatures to the 41-43?C range that can selectively inhibit cancer cell growth. We conjugated IR820 with PEG-diamine via ionic interactions to create nanoconjugates (IR820-PDNCs) with diameters of approximately 50-nm per SEM and a zeta potential of 2.0±0.9 mV. IR820-PDNCs enhanced cellular internalization compared to IR820 for imaging in SKOV-3, MES-SA, and Dx5 cancer cells. The nanoconjugates also significantly enhanced hyperthermia-mediated cytotoxicity in MES-SA and Dx5 compared to the free dye (p<0.05). Covalent conjugation of IR820 with PEG-diamine for further stabilization resulted in nanoconjugates (IRPDcov) that have potential for in vivo applications. Our IRPDcov formulation retained the ability to fluoresce and to cause hyperthermia-mediated cellgrowth inhibition, with enhanced internalization and significantly enhanced cytotoxic hyperthermia effects compared to free dye. Additionally, IRPDcov demonstrated significantly longer (p<0.05) plasma half-lives, elimination half-lives, and area-underthe-curve values compared to IR820, indicating larger overall exposure to the theranostic agent. The IRPDcov conjugate had different organ localization than free IR820, with potential reduced accumulation in the kidneys and significantly lower (p<0.05) accumulation in the lungs. Some potential advantages of IR820-PEG-diamine nanoconjugates 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, targeting, and customization. The conjugation of PEG-diamine with a NIR dye provides a multifunctional delivery vector whose localization can be monitored with noninvasive techniques and that may also serve for guided hyperthermia cancer treatments.
Fernandez Fernandez, Alicia, "IR820 nanoconjugates for theranostic applications" (2013). ProQuest ETD Collection for FIU. AAI3567266.