IR820 conjugates for image-guided cancer therapy Conference

Fernandez-Fernandez, A, Manchanda, R, Lei, T et al. (2013). IR820 conjugates for image-guided cancer therapy . 39 IFMBE 1636-1639. 10.1007/978-3-642-29305-4_429

cited authors

  • Fernandez-Fernandez, A; Manchanda, R; Lei, T; Srinivasan, S; McGoron, AJ

abstract

  • The development of novel agents for multifunctional approaches to cancer diagnosis and therapy is a growing area of research with great promise for clinical translation. Our group has created two conjugate formulations of the near-infrared dye IR820 that can be used as image-guided therapy agents. The first formulation combined IR820 with PEG-diamine to create ionic IR820-PEG diamine nanoplexes (IR820-PDNCs), and the second formulation was a covalent conjugate of IR820 and chitosan (IR820-chitosan). Both formulations retained the ability to fluoresce and generate heat upon laser exposure. IR820-PDNCs, approximately 50-nm in diameter, were characterized and studied in vitro using the cancer cell lines MES-SA, Dx5, and SKOV-3. Fluorescent imaging after 2.5-hour incubation with IR820-PDNCs showed enhanced cell uptake compared to free IR820 dye. Cytotoxicity studies showed an enhanced cytotoxic effect of IR820-PDNCs after exposure to 808-nm when compared to the use of free IR820 for all three cell lines. This enhancement was statistically significant in MES-SA and Dx5 (p<0.05). IR820-chitosan conjugates were characterized for their absorption and fluorescence properties and studied in vitro using the same cell lines as for IR820-PDNCs. The IR820-conjugate formulation was also studied in vivo using a Fisher-344 rat model. Our results showed that IR820-chitosan conjugates can be used in cell imaging and have an enhanced hyperthermia- mediated cytotoxic effect in MES-SA and Dx5 compared to free dye (p<0.05). During in vivo studies, IR-820 conjugates accumulated in the liver after an i.v. injection, and were subsequently excreted in bile. The conjugates traveled through the intestines and retained the ability to fluoresce for at least 24 hours. This indicates that IR820-chitosan conjugates may have applications as gastrointestinal contrast agents or delivery vehicles. Both IR820 conjugate formulations have the potential to be further developed as theranostic agents. © 2013 Springer-Verlag.

publication date

  • April 16, 2013

Digital Object Identifier (DOI)

International Standard Book Number (ISBN) 13

start page

  • 1636

end page

  • 1639

volume

  • 39 IFMBE