Water‐Dispersed Near‐Infrared‐Emitting Quantum Dots of Ultrasmall Sizes for In Vitro and In Vivo Imaging

Abstract

Near-infrared (NIR)-fluorescence imaging is widely recognized as an effective method for high-resolution and highsensitivity bioimaging because of its minimized biological autofluorescence background and the increased penetration of excitation and emission light through tissues in the NIR wavelength window (700–900 nm). There have been tremendous efforts to develop high-efficiency fluorescent biological probes for NIR-fluorescence imaging. Semiconductor quantum dots (QDs) have attracted much recent attention as a new generation of fluorescent probes because of their unique optical properties such as strong luminescence, high photostability, and size-tunable emission wavelength. While QDs emitting in the range of 450–650 nm have been well developed, NIR-emitting QDs have been much less explored because of their relatively complicated synthesis and post-treatment manipulations. Furthermore, NIR-emitting QDs are usually prepared in organic phase, and additional surface modification is employed to render them waterdispersible for biological applications. The relatively complicated surface modification often results in an increase in size of the QDs. Only recently, water-dispersed NIRemitting CdTe/CdS QDs with tetrahedral structure were directly prepared in aqueous phase through the epitaxialshell-growth method. Despite these advances, much work is still needed to obtain NIR-emitting QDs that can be facilely synthesized in aqueous phase for high-sensitivity and specific bioimaging. Herein, we report the first example of ultrasmall-sized NIR-emitting CdTe QDs with excellent aqueous dispersibility, robust storage, chemical, and photostability, and strong photoluminescence (photoluminescent quantum yield (PLQY): 15–20%). Significantly, the NIR QDs are directly synthesized in aqueous phase through a facile one-step microwave-assisted method (see the Supporting Information for experimental details and mechanisms) by utilizing several attractive properties of microwave irradiation such as prompt startup, easy heat control (on and off), prompt and homogeneous heating, and so forth. More importantly, highly spectrally and spatially resolved bioimaging was possible, and efficient tumor passive targeting in live mice was shown by using the prepared QDs. QDs with different emission wavelengths in the NIR range (lmax= 700–800 nm) can be readily prepared through fine adjustment of the experimental conditions (e.g., reaction time and temperature). Figure 1a,b displays the normalized ultraviolet photoluminescence (UV-PL) spectra for a series of as-prepared QDs with controllable maximum emission wavelength ranging from 700 to 800 nm in aqueous solution. Such QD solutions are transparent under ambient light conditions, suggesting the as-prepared QDs are well-dispersed in aqueous phase without further treatment (Figure 1c). The excellent aqueous dispersibility of the QDs arises from the surfacecovering mercaptopropionic acid (MPA) that acts as a stabilizer because of the presence of negatively charged carboxylic groups. Under UV irradiation the fluorescence of the as-prepared QDs became darker and the emission wavelength gradually shifted out of the visible region (Figure 1d). The transmission electron microscopy (TEM) and highresolution TEM (HRTEM) images reveal that the NIRemitting QDs are spherical particles with good monodispersibility (Figure 2a,b). The existence of a well-resolved crystal lattice in the HRTEM image further confirms the highly crystalline structures of the QDs (Figure 2b inset). Furthermore, the size distribution histogram (Figure 2c), which was determined by measuring more than 250 particles, shows that the average size and standard deviation of the as-prepared NIR-emitting QDs is (3.74 0.67) nm. Comparatively, the [*] Prof. Y. He, Y. L. Zhong, Dr. Y. Y. Su, Y. M. Lu, Z. Y. Jiang, F. Peng, T. T. Xu, Dr. S. Su Institute of Functional Nano & Soft Materials (FUNSOM) and Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University Suzhou, Jiangsu 215123 (China) Fax: (+86)512-6588-2846 E-mail: yaohe@suda.edu.cn