Functionalized rare earth-doped nanoparticles for breast cancer nanodiagnostic using fluorescence and CT imaging

Breast cancer is the second leading cause of cancer death among women and represents 14% of death in women around the world. The standard diagnosis method for breast tumor is mammography, which is often related with false-negative results leading to therapeutic delays and contributing indirectly to the development of metastasis. Therefore, the development of new tools that can detect breast cancer is an urgent need to reduce mortality in women. Here, we have developed Gd₂O₃:Eu³⁺ nanoparticles functionalized with folic acid (FA), for breast cancer detection.

Gd₂O₃:Eu³⁺ nanoparticles were synthesized by sucrose assisted combustion synthesis and functionalized with FA using EDC-NHS coupling. The FA-conjugated Gd₂O₃:Eu³⁺ nanoparticles exhibit strong red emission at 613 nm with a quantum yield of ~ 35%. In vitro cytotoxicity studies demonstrated that the nanoparticles had a negligible cytotoxic effect on normal 293T and T-47D breast cancer cells. Cellular uptake analysis showed significantly higher internalization of FA-conjugated RE nanoparticles into T-47D cells (Folr ^hi ) compared to MDA-MB-231 breast cancer cells (Folr ^lo ). In vivo confocal and CT imaging studies indicated that FA-conjugated Gd₂O₃:Eu³⁺ nanoparticles accumulated more efficiently in T-47D tumor xenograft compared to the MDA-MB-231 tumor. Moreover, we found that FA-conjugated Gd₂O₃:Eu³⁺ nanoparticles were well tolerated at high doses (300 mg/kg) in CD1 mice after an intravenous injection. Thus, FA-conjugated Gd₂O₃:Eu³⁺ nanoparticles have great potential to detect breast cancer.

Our findings provide significant evidence that could permit the future clinical application of FA-conjugated Gd₂O₃:Eu³⁺ nanoparticles alone or in combination with the current detection methods to increase its sensitivity and precision.