Abstract

Ribonuclease-A (RNase-A) encapsulated PbS quantum dots (RNase-A@PbS Qdots) which emit in the second near-infrared biological window (NIR-II, ca. 1000–1400 nm) are rapidly synthesized under microwave heating. Photoluminescence (PL) spectra of the Qdots can be tuned across the entire NIR-II range by simply controlling synthesis temperature. The size and morphology of the Qdots are examined by transmission electron microscopy (TEM), atomic force microscopy (AFM), and dynamic light scattering (DLS). Quantum yield (Φf) measurement confirms that the prepared Qdots are one of the brightest water-soluble NIR-II emitters for in vivo imaging. Their high Φf (∼17.3%) and peak emission at ∼1300 nm ensure deep optical penetration to muscle tissues (up to 1.5 cm) and excellent imaging contrast at an extremely low threshold dose of ∼5.2 pmol (∼1 μg) per mouse. Importantly, this protein coated Qdot displays no signs of toxicity toward model neuron, normal, and cancer cells in vitro. In addition, the animal’s metabolism results in thorough elimination of intravenously injected Qdots from the body within several days via the reticuloendothelial system (RES), which minimizes potential long-term toxicity in vivo from possible release of lead content. With a combination of attractive properties of high brightness, robust photostability, and excellent biocompatibility, this new NIR-II emitting Qdot is highly promising in accurate disease screening and diagnostic applications.

Highlights

  • Over the past 20 years, fluorescent semiconductor nanocrystals, known as quantum dots (Qdots), have emerged as a powerful probe for biology because of their unique, sizedependent, bright, and stable fluorescence.[1−5] In particular, Qdots that emit in the second near-infrared biological window (NIR-II, 1000−1400 nm, photon energy 1.24−0.89 eV) are extremely attractive for in vivo fluorescence imaging

  • We have previously demonstrated that ribonuclease-A (RNase-A), a small monomeric protein (Mw ∼13.7 kDa), can template the synthesis of highly fluorescent gold nanoclusters[29] and CdTe Qdots[30] for cellular imaging in the NIR-I and visible region, respectively

  • A microwave assisted approach has been developed for rapid synthesis of well-dispersed, highly fluorescent, and biocompatible RNase-A capped PbS Qdots in aqueous phase

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Summary

■ INTRODUCTION

Over the past 20 years, fluorescent semiconductor nanocrystals, known as quantum dots (Qdots), have emerged as a powerful probe for biology because of their unique, sizedependent, bright, and stable fluorescence.[1−5] In particular, Qdots that emit in the second near-infrared biological window (NIR-II, 1000−1400 nm, photon energy 1.24−0.89 eV) are extremely attractive for in vivo fluorescence imaging. The biodistribution and imaging studies of the RNase-A@PbS Qdots are performed on nude mice (n = 3) by intravenous administration.[38] Prior to injection, the mouse displays negligible fluorescence background under 808 nm laser excitation (Figure 7b), whereas an intense fluorescence signal is detected in the superficial vasculature throughout the mouse’s body at 5 min postinjection of the Qdots (200 μL at 26 nM, total Qdot dose = 5.2 pmol or ∼1.0 μg core weight), with the strongest signal appearing in the spleen (Figure 7c). The Qdot dose per mouse used is about 5.2 pmol (or ∼1 μg core weight), which is substantially lower (by ∼40−600 fold) than other NIR-II emitting Qdots used for in vivo imaging (see Table 2) This ultralow dosage is a clear reflection of superior brightness of our RNase-A@PbS Qdot, which is important to reduce the risk of potential lead exposure.

■ CONCLUSIONS
■ ACKNOWLEDGMENTS
■ REFERENCES
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