Size Series of Small Indium Arsenide−Zinc Selenide Core−Shell Nanocrystals and Their Application to In Vivo Imaging

Abstract

We have developed a size series of unusually small, water-soluble (InAs)ZnSe (core)shell quantum dots (QDs) that emit in the near infrared and exhibit new behavior in vivo, including multiple sequential lymph node mapping and extravasation from the vasculature. The biological utility of these fluorescent probes resulted from our intentional choice to match the semiconductor material and water soluble ligand with a desired final hydrodynamic diameter and emission wavelength.Semiconductor nanocrystals (or quantum dots, QDs) are excellent fluorophores due to their continuous absorption profiles at wavelengths to the blue of the band edge, high photostability, and narrow, tunable emission peaks. For in vivo biological imaging applications, the QD emission wavelength should ideally be in a region of the spectrum where blood and tissue absorb minimally but detectors are still efficient, approximately 700-900 nm in the near infrared (NIR). 1 In addition, the hydrodynamic size of the QD should be appropriately matched to the biological experiment of interest. 2 In previous work, for example, we described the efficacy of Type II QDs with hydrodynamic diameters (HD) of 15.8-18.8 nm to map sentinel lymph nodes selectively. 2a Here we report the synthesis of a size series of (InAs)ZnSe (core) shell QDs that emit in the near infrared and exhibit HD < 10 nm. We demonstrate their utility E-mail: mgb@mit.ed. Supporting Information Available: Experimental procedures, transmission electron microscopy data, and additional optical characterization, including emission stability in serum. in vivo by imaging multiple, sequential lymph nodes and showing extravasation from the vasculature in rat models, neither of which has been achieved before with QDs to our knowledge. NIH Public AccessWhile InAs QDs are known, most studies report emission wavelengths longer than 800 nm. 3 Until now, only Battaglia and Peng have shown well defined InAs first absorptioin peaks at wavelengths below 800 nm. 4 Their work, however, primarily concerned InP QDs. We have developed a procedure for the synthesis of a well-characterized size series of small InAs cores (diameters < 2 nm). Moreover we have extended the work to show the overcoating of these very small cores with a second, higher bandgap semiconductor shell. Zinc selenide was chosen as the ideal shell material due to its reasonably small lattice mismatch with zinc blende InAs (6.44%), its high bulk band offsets (1.26 and 0.99 eV for the conduction and valence bands, CB and VB, respectively), and its reported ability to increase the quantum yield (QY) of InAs cores by more than an order of magnitude. 3e Longer emission wavelengths, particularly the biologically desirable 800-840 nm range, can be achieved by (1) increasing the core size or (2) the shell thickness, or (3) by altering the band offsets between core and shell such as by adding a small amount of Cd to the ZnSe shell. Therefore, by varying the core size, and the shell thickness or composition, a wide tunability of the final emissi...

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