Elsevier

Biomaterials

Volume 33, Issue 29, October 2012, Pages 7071-7083
Biomaterials

The therapeutic efficacy of CdTe and CdSe quantum dots for photothermal cancer therapy

https://doi.org/10.1016/j.biomaterials.2012.06.062Get rights and content

Abstract

Fluorescent quantum dots (QDs) used for biomedical imaging and diagnostics have attracted considerable attention over the past decade. Here, we report our finding regarding the therapeutic efficacy of the popularly used red/brown, brown or close to black CdTe and CdSe QDs. Upon 671-nm laser irradiation, these QDs can rapidly convert light energy into heat, both in vitro and in vivo. In the present study, the growth of mouse melanoma tumors injected with CdTe(710) QDs coated with a silica shell (SiO2) was significantly inhibited after laser irradiation, with eventual disappearance of the tumor. In contrast, tumors injected with the silica-coated QDs without subsequent irradiation continued to grow over time. They had a growth rate close to that of tumors injected with SiO2 or phosphate-buffered saline, with or without laser irradiation. In conclusion, our data suggest that the popularly used CdTe and CdSe QDs have great potential in the treatment of cancer using photothermal therapy.

Introduction

Recently, quantum dots (QDs) have drawn a great deal of attention owing to their interesting photophysical properties that include high fluorescence quantum yield (QY), superior stability against photobleaching, a narrow and symmetric emission spectrum and a broad and continuous excitation spectrum [1], [2], [3]. These properties make QDs superior fluorescent probes to organic fluorescent dyes and proteins for in vitro and in vivo biomedical imaging [4], [5]. In addition, QDs have potential in cancer photodynamic therapy as photosensitizers, since ultraviolet (UV) light irradiation can induce them to generate reactive oxygen species (ROS) such as ·OH and O2, cytotoxic single oxygen (1O2) and toxic heavy metal ions [6], [7], [8]. However, for well-protected QDs the shells (such as ZnS) on the QD surface create higher energy barriers between oxidizing molecules and the QD cores, preventing the effective production of ROS [9], [10]. It has been demonstrated that the level of ROS produced by the QDs is lower than that produced by classic photosensitizers [6], [11]. Therefore, although the use of QDs as cancer therapy agents has attracted attention, most of the work concerning QD biomedical applications as of yet has been focused on fluorescence imaging.

In recent years, CdTe and CdSe nanocrystals have been the most prominent QDs used for life science applications [5], because they exhibit higher fluorescent QYs and can be synthesized using a simpler strategy (e.g. CdTe QDs with >70% QY can be conveniently prepared in aqueous solution [12]) than III/V group or ternary QDs such as InP and InGaP. In the present study, we report on a unique property of the popularly used CdTe and CdSe QD aqueous solutions with red/brown, brown or close to black colors in bright fields (especially the latter two deep colors), namely that they can rapidly convert light energy into heat after laser irradiation. This property is potentially useful for cancer photothermal therapy, and was evaluated in the present study using a mouse melanoma tumor model.

Section snippets

Chemicals

CdCl2·2.5H2O, Na2SO3, Te and Se powders, NaBH4, citrate acid, tetraethyl orthosilicate (TEOS), ethanol and hematoxylin and eosin (H&E) were purchased from Sinopharm Chemical Reagent Co., Ltd. (Shanghai, China). 3-Mercaptopropionic acid (MPA) and paraformaldehyde were purchased from Sigma–Aldrich Corporation. 2,7-Dichlorodihydrofluorescein diacetate (DCFH-DA) was purchased from Beyotime Institute of Biotechnology (Jiangsu, China). CellTiter-Glo® luminescent cell viability assay reagents were

Optical properties of the CdTe QDs

In order to investigate how the QD colors affected the photothermal converting efficiency, six-colored CdTe QDs which were synthesized in aqueous solutions, were used in our study. When 2 mg/mL of the CdTe QD solutions were exposed to sunlight, they exhibited yellowish green, orange, red, red/brown, brown and deep brown (or close to black) colors. Their fluorescent colors also differed, ranging from green to deep red (Fig. 1A). The maximum fluorescent emissions from the QDs were located at 534,

Conclusions

In summary, the current study showed that the popularly used fluorescent CdTe and CdSe QDs, with red/brown, brown or deep brown (close to black) colors, could effectively convert light energy into heat both in vitro and in vivo when activated by 671-nm laser irradiation. The deeper the QD color was, the higher was the increase in temperature after irradiation. In addition, the QDs as well as the silica-coated QDs could effectively generate intracellular ROS after laser irradiation. And the

Acknowledgments

The authors would like to gratefully acknowledged Dr. Alexander Endler for critically reading the manuscript and stimulating discussions. This work was supported in part by the Key Technologies R&D Program in the 11th Five-year Plan of China (2009ZX09103-701) and National Natural Science Foundation of China (No. 81071833).

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