Self-illuminating quantum dot conjugates for in vivo imaging

• Published in: Nature biotechnology Vol. 24; no. 3; pp. 339 - 343
• Main Authors: So, Min-Kyung, Xu, Chenjie, Loening, Andreas M, Gambhir, Sanjiv S, Rao, Jianghong
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2006; Nature; Nature Publishing Group
• Subjects: Agriculture; Animals; Bioinformatics; Biological and medical sciences; Bioluminescence; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Diagnostic Imaging; Diverse techniques; Energy Transfer; Enzymes; Fluorescence; Fundamental and applied biological sciences. Psychology; letter; Life Sciences; Luciferases - genetics; Luciferases - metabolism; Luminescent Measurements - methods; Mice; Mice, Nude; Microscopy, Fluorescence; Molecular and cellular biology; Quantum Dots; Renilla reniformis; Resonance; Scientific imaging; Semiconductors; Sensitivity and Specificity; Bioluminescence; Quantum dot; Semiconductor materials; Enzyme; Luciferase; Fluorescence; Imagery; In vivo; Tissue; Resonant energy transfer; Animal; Oxidoreductases; Conjugated compound
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt1188

Fluorescent semiconductor quantum dots hold great potential for molecular imaging in vivo 1 , 2 , 3 , 4 , 5 . However, the utility of existing quantum dots for in vivo imaging is limited because they require excitation from external illumination sources to fluoresce, which results in a strong autofluorescence background and a paucity of excitation light at nonsuperficial locations. Here we present quantum dot conjugates that luminesce by bioluminescence resonance energy transfer in the absence of external excitation. The conjugates are prepared by coupling carboxylate-presenting quantum dots to a mutant of the bioluminescent protein Renilla reniformis luciferase. We show that the conjugates emit long-wavelength (from red to near-infrared) bioluminescent light in cells and in animals, even in deep tissues, and are suitable for multiplexed in vivo imaging. Compared with existing quantum dots, self-illuminating quantum dot conjugates have greatly enhanced sensitivity in small animal imaging, with an in vivo signal-to-background ratio of > 10 3 for 5 pmol of conjugate.