We report development of theranostic conjugates for dual application in targeted anti-cancer therapy and near infrared fluorescent imaging. A new polyaminocarboxylate-based cytotoxic chelating agent (CAB-NE3TA) was synthesized and evaluated for inhibitory activity against melanoma (A375), cervical (HeLa), colon cancer (HT29 and LS174T), breast cancer (MDA-MB231), ovary cancer (SKOV-3), liver cancer (HepG2) cells. The new anti-tumor agent was significantly potent in destroying the cancer cells when compared to the clinically available iron chelating anti-tumor agent (DFO). Encouraged by the in vitro cytotoxicity data, we then designed a theranostic platform (CAB-NE3TA-PAN-IR800) constructed on an internalizing EGFR-targeted antibody (panitumumab, PAN) labeled with a near IR fluorescent dye. We also built the first atomistic model of the EGFR-PAN complex and loaded it with the cytotoxic CAB-NE3TA and the near IR dye. The theranostic conjugate was evaluated for in vivo biodistribution and anti-tumor activity using a mouse model of colorectal cancer and displayed highly selective tumor uptake and rapid blood and organ clearance. The in vitro and in vivo data suggest potential theranostic applications of CAB-NE3TA-based protein conjugates for simultaneous therapy and imaging of cancers.

Theranostic antibody-drug conjugates for potential dual application in targeted therapy and fluorescence imaging of colorectal cancer

256th National Meeting (2018)

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