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In vivo cancer targeting and imaging with semiconductor quantum dots

Abstract

We describe the development of multifunctional nanoparticle probes based on semiconductor quantum dots (QDs) for cancer targeting and imaging in living animals. The structural design involves encapsulating luminescent QDs with an ABC triblock copolymer and linking this amphiphilic polymer to tumor-targeting ligands and drug-delivery functionalities. In vivo targeting studies of human prostate cancer growing in nude mice indicate that the QD probes accumulate at tumors both by the enhanced permeability and retention of tumor sites and by antibody binding to cancer-specific cell surface biomarkers. Using both subcutaneous injection of QD-tagged cancer cells and systemic injection of multifunctional QD probes, we have achieved sensitive and multicolor fluorescence imaging of cancer cells under in vivo conditions. We have also integrated a whole-body macro-illumination system with wavelength-resolved spectral imaging for efficient background removal and precise delineation of weak spectral signatures. These results raise new possibilities for ultrasensitive and multiplexed imaging of molecular targets in vivo.

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Figure 1: Schematic illustration of biconjugated QDs for in vivo cancer targeting and imaging.
Figure 2: Immunocytochemical studies of QD-PSMA Ab binding activity in cultured prostate cancer cells.
Figure 3: Histological examination of QD uptake, retention and distribution in six different normal host organs and in C4-2 tumor xenografts maintained in athymic nude mice.
Figure 4: Spectral imaging of QD-PSMA Ab conjugates in live animals harboring C4-2 tumor xenografts.
Figure 5: In vivo fluorescence images of tumor-bearing mice using QD probes with three different surface modifications: carboxylic acid groups (left), PEG groups (middle) and PEG-PSMA Ab conjugates (right).
Figure 6: Sensitivity and multicolor capability of QD imaging in live animals.

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Acknowledgements

This work was supported by grants to S.N. and L.W.K.C. from the National Institutes of Health (R01 GM60562 to S.N. and P01 CA098912 to L.W.K.C.), the Georgia Cancer Coalition (Distinguished Cancer Scholar Awards), the Coulter Translational Research Program at Georgia Tech and Emory University and the Department of Defense (17-03-2-0033 to L.W.K.C.). We acknowledge Lily Yang and Binfei Zhou for technical help, and Fray F. Marshall, John A. Petros, Hyunsuk Shim and Jonathan W. Simons for stimulating discussions. We are also grateful to Millennium Pharmaceuticals for providing the PSMA monoclonal antibody (J591).

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Correspondence to Leland W K Chung or Shuming Nie.

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Supplementary information

Supplementary Fig. 1

Comparison of red-emitting QDs and red organic dyes for in vivo optical imaging. (PDF 54 kb)

Supplementary Fig. 2

Comparison of mouse skin and QD emission spectra. (PDF 159 kb)

Supplementary Notes (PDF 29 kb)

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Gao, X., Cui, Y., Levenson, R. et al. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol 22, 969–976 (2004). https://doi.org/10.1038/nbt994

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