Application of functional quantum dot nanoparticles as fluorescence probes in cell labeling and tumor diagnostic imaging
© Zhao and Zeng; licensee Springer. 2015
Received: 30 January 2015
Accepted: 21 March 2015
Published: 10 April 2015
Quantum dots (QDs) are a class of nanomaterials with good optical properties. Compared with organic dyes, QDs have unique photophysical properties: size-tunable light emission, improved signal brightness, resistance against photobleaching, and simultaneous excitation of multiple fluorescence colors. Possessing versatile surface chemistry and superior optical features, QDs are useful in a variety of in vitro and in vivo applications. When linked with targeting biomolecules, QDs can be used to target cell biomarkers because of high luminescence and stability. So QDs have the potential to become a novel class of fluorescent probes. This review outlines the basic properties of QDs, cell fluorescence labeling, and tumor diagnosis imaging and discusses the future directions of QD-focused bionanotechnology research in the life sciences.
Quantum dots (QDs) are a kind of semiconductor fluorescent semiconductors, which have gained attraction in recent years by scientists as a novel fluorescent probe [1-6]. Compared with conventional organic fluorescent probes, QDs have shown great potential to be fluorescent probes and images in biology because of their unique optical properties [7-15]. Alivisatos and Nie employed QDs as fluorescent probes in biological staining and diagnostics that provided a novel study to display QDs as labels for cell and tissue research [16,17]. In recent years, QDs have been widely used in many fields of life sciences as fluorescent markers [18-21]. Herein, we briefly review the basic properties of QDs and the application of functionalized QDs as fluorescent probes in biological systems.
The unique properties of quantum dots
QDs have unique optical and electrical properties due to its quantum effect and size effect. When the size of a particle is of nanometer scale, it will cause quantum confinement effect, size effect, dielectric confinement effect, macroscopic quantum effect, and surface effect. Consequently, QDs exhibit many optical properties different from macroscopic materials, and they have a very broad application prospects in biological fluorescent probes and functional materials. Therefore, QDs will have a meaningful effect on the continued development of life sciences [22-28].
Quantum dots have unique optical properties
Quantum dots have large stokes shift
Quantum dots have strong fluorescence intensity and high stability and strong resistance ability to photobleaching
Quantum dots have long fluorescence lifetime
The fluorescence lifetime of typical organic fluorescent dyes is only a few nanoseconds (ns), which is similar to the decay time of autofluorescence of biological samples. While the fluorescence lifetime of QDs can sustain tens of nanoseconds (20 to 50 ns), which makes the fluorescence of QDs still persist and obtain fluorescence signals without background interference when the majority of the auto-fluorescence background has been attenuated after a few nanoseconds of light excitation [39,40].
Quantum dots have good biocompatibility
The chemically modified QDs are less harmful to organisms with good biocompatibility and low cytotoxicity. And it is easy to achieve QD surface functionalization of specific connection and biological labeling and detection in vivo after a variety of chemical modifications .
Since the surface chemical properties of the same kind of fluorescent nanoparticles of different sizes are very similar, the chemical modification method for particles of one size can also be applied to other sizes of particles, making it easy to obtain a series of fluorescent marking materials of the same surface-modified structure but of different optical properties, which greatly simplifies the biochemical modification process of fluorescent probes . In addition, QDs are of good spatial compatibility, a QD can simultaneously couple two or more biological molecules or ligands, so QDs can be used to prepare multifunctional materials for detection and imaging [43,44]. Because of these unique optical properties, QDs can be used as ideal fluorescent probes . And instead of organic fluorescent dyes, QDs will play an important role in the study in the cellular location, signal transduction, intracellular molecular movement, and migration [46,47].
The applications of quantum dots in cell labeling and imaging
The most promising application of QDs is that they can be used as fluorescent probes in biological systems. QDs made of different materials coupled with biological molecules can replace a lot of fluorescent dye molecules and play a significant role in cell biology research. And the light stability of QD markers makes long-term tracking of biological molecules possible, using the labeling technique [48,49].
In the biomedical field, one of the earliest and most successful applications of QDs is in cell biology research; for example, QDs can be used as cell surface markers and intracellular markers . Cell surface markers are obtained by specifically binding QDs with biomolecules to cell surface by streptavidin-biotin system, and the QDs are indirectly marked on cell surface. Based on the fact that green silanized QDs have the characteristics of high affinity with nuclei, Alivisatos et al. directly marked murine fibroblast cell nuclei using the QDs . Taking advantage of electrostatic interactions, they connected avidin to the surface of red silanized QDs and labeled QDs to the F-actin on cell surface by the specificity of biotin-avidin. So, for the first time, the two-color QDs marked individual cells simultaneously.
The applications of quantum dots in tumor diagnostic
Cervical cancer is one of the most fatal diseases, and researchers are actively developing methods of early diagnosis and treatment. Currently, QDs have been successfully applied to tumor imaging at the cellular level. Rahman et al.  combined overexpression SiHa cervical cancer cells of epidermal growth factor receptor (EGFR) with the monoclonal antibody of biotinylated EGFR and found that the fluorescence intensity of the experimental group was significantly higher than that of the control group after being irradiated by two kinds of excitation light of the confocal fluorescence microscopy. And the tumor cells could be identified from the full organization by the QD probes, which have a more competitive advantage than the traditional contrast agents. It proved that QD probes can detect cervical cancer at the molecular level, which provides a new way for early diagnosis of cervical cancer. The strong fluorescent stability of QDs also shows superiority in research on living animal. In recent years, Ren et al. have reported CdSeTeS QDs modified with alpha-thio-omega-carboxy poly(ethylene glycol) (HS-PEG-COOH), and the modified QDs were linked to anti-epidermal growth factor receptor (EGFR) antibodies . QDs with the EGFR antibodies as labeling probes were successfully applied to targeted imaging for EGFR on the surface of SiHa cervical cancer cells through conjugation of QDs with the anti-EGFR antibodies. These preliminary results indicated that CdSeTeS QDs can become useful probes for in vivo targeted imaging and clinical diagnosis.
With the development of nanotechnology and the improvement of QD marking technology, QDs are increasingly showing its great value and good prospects, especially in the optical and biological aspects, due to their unique physical and chemical properties. Certainly, far more than this, QDs are also a powerful tool for drug screening. QDs will become the most promising fluorescent markers; for example, QDs show great potential for cell imaging, fluorescence immunoassay, etc. Especially, QDs have made great progress in the cellular imaging in recent years, showing far more advantages than the traditional organic dyes. The technology of using QDs as fluorescent markers of living cells is gradually becoming mature, diverse, and practical. It can be predicted that the QD fluorescence technology will open up new horizons for researches in complicated life phenomena of living cells.
This work was supported by the National Natural Science Foundation of China (U1204201), Postdoctoral Science Surface Foundation of China (No. 2012 M511570), and Department of Education Science and Technology Research Key Projects of Henan (13A150063).
- Yong K-T, Law W-C, Hu R, Ye L, Liu L, Swihart MT, et al. Nanotoxicity assessment of quantum dots: from cellular to primate studies. Chem Soc Rev. 2013;42:1236–50.View ArticleGoogle Scholar
- Park Y, Ryu YM, Jung Y, Wang T, Baek Y, Yoon Y, et al. Spraying quantum dot conjugates in the colon of live animals enabled rapid and multiplex cancer diagnosis using endoscopy. ACS Nano. 2014;8:8896–910.View ArticleGoogle Scholar
- Biju V. Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy. Chem Soc Rev. 2014;43:744–64.View ArticleGoogle Scholar
- Taniguchi S, Green M, Rizvi SB, Seifalian A. The one-pot synthesis of core/shell/shell CdTe/CdSe/ZnSe quantum dots in aqueous media for in vivo deep tissue imaging. J Mater Chem. 2011;21:2877–82.View ArticleGoogle Scholar
- Chakraborty A, Jana NR. Design and synthesis of triphenylphosphonium functionalized nanoparticle probe for mitochondria targeting and imaging. J Phys Chem C. 2015;119:2888–95.Google Scholar
- He X, Ma N. An overview of recent advances in quantum dots for biomedical applications. Colloids Surf B: Biointerfaces. 2014;124:118–31.View ArticleGoogle Scholar
- Wu P, Yan X-P. Doped quantum dots for chemo/biosensing and bioimaging. Chem Soc Rev. 2013;42:5489–521.View ArticleGoogle Scholar
- Esteve-Turrillas FA, Abad-Fuentes A. Applications of quantum dots as probes in immunosensing of small-sized analytes. Biosens Bioelectron. 2013;41:12–29.View ArticleGoogle Scholar
- Viswanath A, Shen Y, Green AN, Tan R, Greytak AB, Benicewicz BC. Copolymerization and synthesis of multiply binding histamine ligands for the robust functionalization of quantum dots. Macromolecules. 2014;47:8137–44.View ArticleGoogle Scholar
- Sekhosana KE, Antunes E, Khene S, D’Souza S, Nyokong T. Fluorescence behavior of glutathione capped CdTe@ZnS quantum dots chemically coordinated to zinc octacarboxy phthalocyanines. J Lumin. 2013;136:255–64.View ArticleGoogle Scholar
- Mattoussi H, Palui G, Na HB. Luminescent quantum dots as platforms for probing in vitro and in vivo biological processes. Adv Drug Deliver Rev. 2012;64:138–66.View ArticleGoogle Scholar
- Bai M, Bornhop DJ. Recent advances in receptor-targeted fluorescent probes for in vivo cancer imaging. Curr Med Chem. 2012;19:4742–58.View ArticleGoogle Scholar
- Molaei M. Synthesizing and investigating photoluminescence properties of CdTe and CdTe@CdS core-shell quantum dots (QDs): a new and simple microwave activated approach for growth of CdS shell around CdTe core. Electron Mater Lett. 2015;11:7–12.View ArticleGoogle Scholar
- Aubert T, Soenen SJ, Wassmuth D, Cirillo M, Van Deun R, Braeckmans K, et al. Bright and stable CdSe/CdS@SiO2 nanoparticles suitable for long-term cell labeling. ACS Appl Mater Interfaces. 2014;6:11714–23.View ArticleGoogle Scholar
- Michalet X, Pinaud FF, Bentolila LA, Tsay JM, Doose S, Li JJ, et al. Diagnostics quantum dots for live cells, in vivo imaging, and diagnostics. Science. 2005;307:538–44.View ArticleGoogle Scholar
- Bruchez Jr M, Moronne M, Gin P, Weiss S, Alivisatos AP. Semiconductor nanocrystals as fluorescent biological labels. Science. 1998;281:2013–6.View ArticleGoogle Scholar
- Chan WCW, Nie S. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science. 1998;281:2016–8.View ArticleGoogle Scholar
- Guyot-Sionnest P, Lhuillier E, Liu H. A “mirage” study of CdSe colloidal quantum dot films, Urbach tail and surface states. J Chem Phys. 2012;137:154704.View ArticleGoogle Scholar
- Demchenko AP. Beyond annexin V: fluorescence response of cellular membranes to apoptosis. Cytotechnology. 2013;65:157–72.View ArticleGoogle Scholar
- Taylor A, Wilson KM, Murray P, Fernig DG, Lévy R. Long-term tracking of cells using inorganic nanoparticles as contrast agents: are we there yet? Chem Soc Rev. 2012;41:2707–17.View ArticleGoogle Scholar
- Shinchi H, Wakao M, Nagata N, Sakamoto M, Mochizuki E, Uematsu T, et al. Cadmium-free sugar-chain-immobilized fluorescent nanoparticles containing low-toxicity ZnS-AgInS2 cores for probing lectin and cells. Bioconjug Chem. 2014;25:286–95.View ArticleGoogle Scholar
- Cassette E, Helle M, Bezdetnaya L, Marchal F, Dubertret B, Pons T. Design of new quantum dot materials for deep tissue infrared imaging. Adv Drug Delivery Rev. 2013;65:719–31.View ArticleGoogle Scholar
- Orte A, Alvarez-Pez JM, Ruedas-Rama MJ. Fluorescence lifetime imaging microscopy for the detection of intracellular pH with quantum dot nanosensors. ACS Nano. 2013;7:6387–95.View ArticleGoogle Scholar
- Fang M, Yuan J-P, Peng C-W, Pang D-W, Li Y. Quantum dots-based in situ molecular imaging of dynamic changes of collagen IV during cancer invasion. Biomaterials. 2013;34:8708–17.View ArticleGoogle Scholar
- Au GH. Shih WY, Shih WH, Mejias L, Swami VK, Wasko K, et al. Assessing breast cancer margins ex vivo using aqueous quantum dot molecular probes Int J Oncol. 2012;2012:861257.Google Scholar
- Biju V, Itoh T, Ishikawa M. Delivering quantum dots to cells: bioconjugated quantum dots for targeted and nonspecific extracellular and intracellular imaging. Chem Soc Rev. 2010;39:3031–56.View ArticleGoogle Scholar
- Orr-Ewing AJ. Perspective: bimolecular chemical reaction dynamics in liquids. J Chem Phys. 2014;140:090901.View ArticleGoogle Scholar
- Li XB, Li ZJ, Gao YJ, Meng QY, Yu S, Weiss RG, et al. Mechanistic insights into the interface-directed transformation of thiols into disulfides and molecular hydrogen by visible-light irradiation of quantum dots. Angew Chem Int Ed Engl. 2014;53:2085–9.View ArticleGoogle Scholar
- Chung H, Choi H, Kim D, Jeong S, Kim J. Size-dependence of excitation energy-related surface trapping dynamics in PbS quantum dots. J Phys Chem C. 2015. doi:10.1021/acs.jpcc.5b01810.Google Scholar
- Painuly D, Bhatt A, Krishnan VK. Mercaptoethanol capped CdSe quantum dots and CdSe/ZnS core/shell: synthesis, characterization and cytotoxicity evaluation. J Biomed Nanotechnol. 2013;9:257–66.View ArticleGoogle Scholar
- Gao XH, Cui YY, Levenson RM, Chung LW, Nie S. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol. 2004;22:969–76.View ArticleGoogle Scholar
- Jaiswal JK, Mattoussi H, Mauro JM, Simon SM. Long-term multiple color imaging of live cells using quantum dot bioconjugates. Nat Biotechnol. 2003;21:47–51.View ArticleGoogle Scholar
- Zrazhevskiy P, Senaw M, Gao X. Designing multifunctional quantum dots for bioimaging, detection, and drug delivery. Chem Soc Rev. 2010;39:4326–654.View ArticleGoogle Scholar
- Pilla V, Alves LP, Iwazaki AN, Andrade AA, Antunes A, Munin E. Thermo-optical characterization of cadmium selenide/zinc sulfide (CdSe/ZnS) quantum dots embedded in biocompatible materials. Appl Spectrosc. 2013;67:997–1002.View ArticleGoogle Scholar
- Gao XH, Yarig L, Petros JA, Marshall FF, Simons JW, Nie S. In vivo molecular and cellular imaging with quantum dots. Curt Opin Biotechnol. 2005;16:63–72.View ArticleGoogle Scholar
- Zrazhevskiy P, Gao XH. Multifunctional quantum dots for personalized medicine. Nano Today. 2009;4:414–28.View ArticleGoogle Scholar
- Lidke DS, Nagy P, Heintzmann R, Arndt-Jovin DJ, Post JN, Grecco HE, et al. Quantum dot ligands provide new insights into erbB/HER receptor-mediated signal transduction. Nat Biotechnol. 2004;22:198–203.View ArticleGoogle Scholar
- Liu H, Xu S, He Z, Deng A, Zhu J-J. Supersandwich cytosensor for selective and ultrasensitive detection of cancer cells using aptamer-DNA concatamer-quantum dots probes. Anal Chem. 2013;85:3385–92.View ArticleGoogle Scholar
- Liu L, Miao Q, Liang G. Quantum dots as multifunctional materials for tumor imaging and therapy. Materials. 2013;6:483–99.View ArticleGoogle Scholar
- Wu XY, Liu HJ, Liu JQ, Haley KN, Treadway JA, Larson JP, et al. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat Biotechnol. 2003;21:41–6.View ArticleGoogle Scholar
- Tomczaka N, Jańczewski D, Hana M, Vancsoa GJ. Designer polymer-quantum dot architectures. Prog Polym Sci. 2009;34:393–430.View ArticleGoogle Scholar
- Saikia K, Deb P, Kalita E. Sensitive fluorescence response of ZnSe(S) quantum dots: an efficient fluorescence probe. Phys Scr. 2013;87:065802.View ArticleGoogle Scholar
- Chi X, Huang D, Zhao Z, Zhou Z, Yin Z, Gao J. Nanoprobes for in vitro diagnostics of cancer and infectious diseases. Biomaterials. 2012;33:189–206.View ArticleGoogle Scholar
- Novio F, Simmchen J, Vázquez-Mera N, Amorín-Ferré L, Ruiz-Molina D. Coordination polymer nanoparticles in medicine. Coord Chem Rev. 2013;257:2839–47.View ArticleGoogle Scholar
- Bilan R, Fleury F, Nabiev I, Sukhanova A. Quantum dot surface chemistry and functionalization for cell targeting and imaging. Bioconjug Chem. 2015, DOI:10.1021/acs.bioconjchem.5b00069.Google Scholar
- Zhong H, Zhang R, Zhang H, Zhang S. Modular design of an ultrahigh-intensity nanoparticle probe for cancer cell imaging and rapid visual detection of nucleic acids. Chem Commun (Camb). 2012;48:6277–9.View ArticleGoogle Scholar
- Sandvig K, Torgersen ML, Engedal N, Skotland T, Iversen TG. Protein toxins from plants and bacteria: probes for intracellular transport and tools in medicine. FEBS Lett. 2010;584:2626–34.View ArticleGoogle Scholar
- Mansur AAP, Ramanery FP, Mansur HS. Water-soluble quantum dot/carboxylic-poly (vinyl alcohol) conjugates: insights into the roles of nanointerfaces and defects toward enhancing photoluminescence behavior. Mater Chem Phys. 2013;141:223–33.View ArticleGoogle Scholar
- Lyashchova A, Dmytruk A, Dmitruk I, Klimusheva G, Mirnaya T, Asaula V. Optical absorption, induced bleaching, and photoluminescence of CdSe nanoplatelets grown in cadmium octanoate matrix. Nanoscale Res Lett. 2014;9:88.View ArticleGoogle Scholar
- Alivisatos AP. Semiconductor clusters, nanocrystals, and quantum dots. Science. 1996;271:933–7.View ArticleGoogle Scholar
- Jie G, Zhao Y, Niu S. Amplified electrochemiluminescence detection of cancer cells using a new bifunctional quantum dot as signal probe. Biosens Bioelectron. 2013;50:368–72.View ArticleGoogle Scholar
- Liu BR, Winiarz JG, Moon J-S, Lo S-Y, Huang Y-W, Aronstam RS, et al. Synthesis, characterization and applications of carboxylated and polyethylene-glycolated bifunctionalized InP/ZnS quantum dots in cellular internalization mediated by cell-penetrating peptides. Colloids Surf B: Biointerfaces. 2013;111:162–70.View ArticleGoogle Scholar
- Chen FQ, Gerion D. Fluorescent CdSe/ZnS nanocrystal-peptide conjugates for long-term, nontoxic imaging and nuclear targeting in living cells. Nano Lett. 2004;4:1827–32.View ArticleGoogle Scholar
- Li Y, Cui R, Zhang P, Chen B-B, Tian Z-Q, Li L, et al. Mechanism-oriented controllability of intracellular quantum dots formation: the role of glutathione metabolic pathway. ACS Nano. 2013;7:2240–8.View ArticleGoogle Scholar
- Gao JH, Xu B. Applications of nanomaterials inside cells. Nano Today. 2009;4:37–51.View ArticleGoogle Scholar
- Zhao M-X, Xia Q, Feng X-D, Mao Z-W, Ji L-N, Wang K. Synthesis, biocompatibility and cell labeling of L-arginine-functional β-cyclodextrin-modified quantum dot probes. Biomaterials. 2010;31:4401–8.View ArticleGoogle Scholar
- Zhao M-X, Huang H-F, Xia Q. Ji L-N. Mao Z-W γ-Cyclodextrin-folate complex-functionalized quantum dots for tumor-targeting and site-specific labeling J Mater Chem. 2011;21:10290–7.Google Scholar
- Lucky SS, Soo KC, Zhang Y. Nanoparticles in photodynamic therapy. Chem Rev. 2015;115:1990–2042.View ArticleGoogle Scholar
- Tak YK, Naoghare PK, Kim BJ, Kim MJ, Lee ES, Song JM. High-content quantum dot-based subtype diagnosis and classification of breast cancer patients using hypermulticolor quantitative single cell imaging cytometry. Nano Today. 2012;7:231–44.View ArticleGoogle Scholar
- Zhao M-X. Ji L-N. Mao Z-W β-Cyclodextrin/glycyrrhizic acid functionalised quantum dots selectively enter hepatic cells and induce apoptosis Chem Eur J. 2012;18:1650–8.Google Scholar
- Rahman M, Abd-El-Barr M, Mack V, Tkaczyk T, Sokolov K, Richards-Kortum R, et al. Optical imaging of cervical pre-cancers with structured illumination: an integrated approach. Gynecol Oncol. 2005;99:S112–5.View ArticleGoogle Scholar
- Yang F, Xu Z, Wang J, Zan F, Dong C, Ren J. Microwave-assisted aqueous synthesis of new quaternary-alloyed CdSeTeS quantum dots; and their bioapplications in targeted imaging of cancer cells. Luminescence. 2013;28:392–400.View ArticleGoogle Scholar
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.