Abstract
Despite all major breakthroughs in recent years of research, we are still unsuccessful to effectively diagnose and treat cancer that has express and metastasizes. Thus, the development of a novel approach for cancer detection and treatment is crucial. Recent progress in Glyconanotechnology has allowed the use of glycans and lectins as bio-functional molecules for many biological and biomedical applications. With the known advantages of quantum dots (QDs) and versatility of carbohydrates and lectins, Glyco-functionalised QD is a new prospect in constructing biomedical imaging platform for cancer behaviour study as well as treatment. In this review, we aim to describe the current utilisation of Glyco-functionalised QDs as well as their future prospective to interpret and confront cancer.

References
Bentolila L A, Ebenstein Y, Weiss S. Quantum dots for in vivo small-animal imaging. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine, 2009, 50(4): 493–496
Byers R J, Hitchman E R. Quantum dots brighten biological imaging. Progress in Histochemistry and Cytochemistry, 2011, 45 (4): 201–237
Tholouli E, Sweeney E, Barrow E, Clay V, Hoyland J, Byers R. Quantum dots light up pathology. Journal of Pathology, 2008, 216 (3): 275–285
He X, Gao J, Gambhir S S, Cheng Z. Near-infrared fluorescent nanoprobes for cancer molecular imaging: Status and challenges. Trends in Molecular Medicine, 2010, 16(12): 574–583
Hilderbrand S A, Weissleder R. Near-infrared fluorescence: Application to in vivo molecular imaging. Current Opinion in Chemical Biology, 2010, 14(1): 71–79
Wang Y, Chen L. Quantum dots, lighting up the research and development of nanomedicine. Nanomedicine (London), 2011, 7 (4): 385–402
Varki A, Cummings R D, Esko J D, Freeze H H, Stanley P, Bertozzi C R, Hart G W, Etzler ME. Essentials of Glycobiology. 3rd ed. New York: Cold Spring Harbor Laboratory Press, 2009
Calvaresi E C, Hergenrother P J. Glucose conjugation for the specific targeting and treatment of cancer. Chemical Science (Cambridge), 2013, 4(6): 2319–2333
Kottari N, Chabre Y M, Sharma R, Roy R. Applications of glyconanoparticles as “sweet” glycobiological therapeutics and diagnostics. In: Multifaceted Development and Application of Biopolymers for Biology, Biomedicine and Nanotechnology. Dutta P K, Dutta J, eds. Berlin: Springer International Publishing, 2013
Marradi M, Chiodo F, Garcia I, Penades S. Glyconanoparticles as multifunctional and multimodal carbohydrate systems. Chemical Society Reviews, 2013, 42(11): 4728–4745
Luczkowiak J, Munoz A, Sanchez-Navarro M, Ribeiro-Viana R, Ginieis A, Illescas B M, Martin N, Delgado R, Rojo J. Glycofullerenes inhibit viral infection. Biomacromolecules, 2013, 14(2): 431–437
Ribeiro-Viana R, Sánchez-Navarro M, Luczkowiak J, Koeppe J R, Delgado R, Rojo J, Davis B G. Virus-like glycodendrinanoparticles displaying quasi-equivalent nested polyvalency upon glycoprotein platforms potently block viral infection. Nature Communications, 2012, 3(1): 1303
Fasting C, Schalley C A, Weber M, Seitz O, Hecht S, Koksch B, Dernedde J, Graf C, Knapp E W, Haag R. Multivalency as a chemical organization and action principle. Angewandte Chemie International Edition, 2012, 51(42): 10472–10498
Liu B, Lu X, Ruan H, Cui J, Li H. Synthesis and applications of glyconanoparticles. Current Organic Chemistry, 2016, 20(14): 1502–1511
Reichardt N C, Martin-Lomas M, Penades S. Glyconanotechnology. Chemical Society Reviews, 2013, 42(10): 4358–4376
Sharon N, Lis H. History of lectins: From hemagglutinins to biological recognition molecules. Glycobiology, 2004, 14(11): 53R–62R
Sharon N, Lis H. Lectins as cell recognition molecules. Science, 1989, 246(4927): 227–234
Ashwell G, Harford J. Carbohydrate-specific receptors of the liver. Annual Review of Biochemistry, 1982, 51(1): 531–554
Belardi B, Bertozzi C R. Chemical lectinology: Tools for probing the ligands and dynamics of mammalian lectins in vivo. Chemistry & Biology, 2015, 22(8): 983–993
André S, Kaltner H, Manning J C, Murphy P V, Gabius H J. Lectins: Getting familiar with translators of the sugar code. Molecules (Basel, Switzerland), 2015, 20(2): 1788–1823
Surolia A, Bachhawat B K, Podder S K. Interaction between lectin from ricinus communis and liposomes containing gangliosides. Nature, 1975, 257(5529): 802–804
Häuselmann I, Borsig L. Altered tumor-cell glycosylation promotes metastasis. Frontiers in Oncology, 2014, 4: 28
Friedel M, Andre S, Goldschmidt H, Gabius H J, Schwartz-Albiez R. Galectin-8 enhances adhesion of multiple myeloma cells to vascular endothelium and is an adverse prognostic factor. Glycobiology, 2016, 26(10): 1048–1058
Compagno D, Gentilini L D, Jaworski F M, Pérez I G, Contrufo G, Laderach D J. Glycans and galectins in prostate cancer biology, angiogenesis and metastasis. Glycobiology, 2014, 24(10): 899–906
Vazquez-Levin MH, Marin-Briggiler C I, Caballero J N, Veiga MF. Epithelial and neural cadherin expression in the mammalian reproductive tract and gametes and their participation in fertilization-related events. Developmental Biology, 2015, 401(1): 2–16
Ng K, Ferreyra J, Higginbottom S, Lynch J, Kashyap P, Gopinath S, Naidu N, Choudhury B, Weimer B, Monack D, Sonnenburg J L. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature, 2013, 502(7469): 96–99
Becer C R. The glycopolymer code: Synthesis of glycopolymers and multivalent carbohydrate-lectin interactions. Macromolecular Rapid Communications, 2012, 33(9): 742–752
Kazunori M, Miki H, Takayasu I, Yoshinao Y, Kazukiyo K. Self-organized glycoclusters along DNA: Effect of the spatial arrangement of galactoside residues on cooperative lectin recognition. Chemistry (Weinheim an der Bergstrasse, Germany), 2004, 10(2): 352–359
Brus L E. Electron-electron and electron-hole interactions in small semiconductor crystallites: The size dependence of the lowest excited electronic state. Journal of Chemical Physics, 1984, 80(9): 4403–4409
Alivisatos A P, Gu W, Larabell C. Quantum dots as cellular probes. Annual Review of Biomedical Engineering, 2005, 7(1): 55–76
Foote M. The importance of planned dose of chemotherapy on time: Do we need to change our clinical practice? Oncologist, 1998, 3(5): 365–368
Naumov G, Akslen L, Folkman J. Role of angiogenesis in human tumor dormancy: Animal models of the angiogenic switch. Cell Cycle (Georgetown, Tex.), 2006, 5(16): 1779–1787
Frangioni J V. New technologies for human cancer imaging. Journal of Clinical Oncology, 2008, 26(24): 4012–4021
Liu J, Levine A L, Mattoon J S, Yamaguchi M, Lee R J, Pan X, Rosol T J. Nanoparticles as image enhancing agents for ultrasonography. Physics in Medicine and Biology, 2006, 51(9): 2179–2189
Massoud T F, Gambhir S S. Molecular imaging in living subjects: Seeing fundamental biological processes in a new light. Genes & Development, 2003, 17(5): 545–580
Albrecht T, Blomley M J K, Burns P N,Wilson S, Harvey C J, Leen E, Claudon M, Calliada F, Correas J M, LaFortune M, et al. Improved detection of hepatic metastases with pulse-inversion US during the liver-specific phase of SHU 508A: Multicenter study. Radiology, 2003, 227(2): 361–370
Blomley M J, Cooke J C, Unger E C, Monaghan M J, Cosgrove D O. Microbubble contrast agents: A new era in ultrasound. BMJ (Clinical Research Ed.), 2001, 322(7296): 1222–1225
Cormode D P, Skajaa T, Fayad Z A, Mulder W J. Nanotechnology in medical imaging: Probe design and applications. Arteriosclerosis, Thrombosis, and Vascular Biology, 2009, 29(7): 992–1000
Weissleder R. Scaling down imaging: Molecular mapping of cancer in mice. Nature Reviews. Cancer, 2002, 2(1): 8–11
Caravan P, Ellison J J, McMurry T J, Lauffer R B. Gadolinium(iii) chelates as MRI contrast agents: Structure, dynamics, and applications. Chemical Reviews, 1999, 99(9): 2293–2352
Hoult D I, Phil D. Sensitivity and power deposition in a high-field imaging experiment. Journal of Magnetic Resonance Imaging, 2000, 12(1): 46–67
Jongmin S, Md A R, Kyeong K M, Ho I G, Hee L J, Su L I. Hollow manganese oxide nanoparticles as multifunctional agents for magnetic resonance imaging and drug delivery. Angewandte Chemie International Edition, 2009, 48(2): 321–324
Smith A M, Duan H, Mohs A M, Nie S. Bioconjugated quantum dots for in vivo molecular and cellular imaging. Advanced Drug Delivery Reviews, 2008, 60(11): 1226–1240
Zhang H, Yee D, Wang C. Quantum dots for cancer diagnosis and therapy: Biological and clinical perspectives. Nanomedicine (London), 2008, 3(1): 83–91
Wang H, Li H, Zhang W, Wei L M, Yu H X, Yang P Y. Multiplex profiling of glycoproteins using a novel bead-based lectin array. Proteomics, 2014, 14(1): 78–86
Munkley J, Elliott D J. Hallmarks of glycosylation in cancer. Oncotarget, 2016, 7(23): 35478–35489
Liu X, Nie H, Zhang Y B, Yao Y F, Maitikabili A, Qu Y P, Shi S L, Chen C Y, Li Y. Cell surface-specific N-glycan profiling in breast cancer. PLoS One, 2013, 8(8): 11
Scott E, Munkley J. Glycans as biomarkers in prostate cancer. International Journal of Molecular Sciences, 2019, 20(6): 20
Andrade C G, Cabral Filho P E, Tenório D P L, Santos B S, Beltrão E I C, Fontes A, Carvalho L B. Evaluation of glycophenotype in breast cancer by quantum dot-lectin histochemistry. International Journal of Nanomedicine, 2013, 8: 4623–4629
He D, Wang D, Shi X, Quan W, Xiong R, Yu C, Huang H. Simultaneous fluorescence analysis of the different carbohydrates expressed on living cell surfaces using functionalized quantum dots. RSC Advances, 2017, 7(20): 12374–12381
Cunha C R A, Andrade C G, Pereira M I A, Cabral Filho P E, Carvalho L B Jr, Coelho L C B B, Santos B S, Fontes A, Correia M T S. Quantum dot-cramoll lectin as novel conjugates to glycobiology. Journal of Photochemistry and Photobiology. B, Biology, 2018, 178: 85–91
Akca O, Unak P, Medine E I, Sakarya S, Yurt Kilcar A, Ichedef C, Bekis R, Timur S. Radioiodine labeled CdSe/CdS quantum dots: Lectin targeted dual probes. Radiochimica Acta, 2014, 102(9): 849
Kara A, Ünak P, Selçuki C, Akça Ö, Medine E İ, Sakarya S. PHA-L lectin and carbohydrate relationship: Conjugation with CdSe/CdS nanoparticles, radiolabeling and in vitro affinities on MCF-7 cells. Journal of Radioanalytical and Nuclear Chemistry, 2014, 299(1): 807–813
Santos B, de Farias P, de Menezes F, de Ferreira R, Júnior S, Figueiredo R, de Carvalho L, Beltrão E I C. CdS-Cd(OH)2 core shell quantum dots functionalized with concanavalin a lectin for recognition of mammary tumors. Physica Status Solidi. C, Current Topics in Solid State Physics, 2006, 3(11): 4017–4022
Ohyanagi T, Nagahori N, Shimawaki K, Hinou H, Yamashita T, Sasaki A, Jin T, Iwanaga T, Kinjo M, Nishimura S I. Importance of sialic acid residues illuminated by live animal imaging using phosphorylcholine self-assembled monolayer-coated quantum dots. Journal of the American Chemical Society, 2011, 133(32): 12507–12517
Bavireddi H, Kikkeri R. Glyco-β-cyclodextrin capped quantum dots: Synthesis, cytotoxicity and optical detection of carbohydrateprotein interactions. Analyst (London), 2012, 137(21): 5123–5127
Shinchi H, Wakao M, Nakagawa S, Mochizuki E, Kuwabata S, Suda Y. Stable sugar-chain-immobilized fluorescent nanoparticles for probing lectin and cells. Chemistry, an Asian Journal, 2012, 7(11): 2678–2682
Shinchi H, Wakao M, Nagata N, Sakamoto M, Mochizuki E, Uematsu T, Kuwabata S, Suda Y. Cadmium-free sugar-chainimmobilized fluorescent nanoparticles containing low-toxicity ZnSAgInS2 cores for probing lectin and cells. Bioconjugate Chemistry, 2014, 25(2): 286–295
Zhai Y, Dasog M, Snitynsky R B, Purkait T K, Aghajamali M, Hahn A H, Sturdy C B, Lowary T L, Veinot J G C. Water-soluble photoluminescent D-mannose and L-alanine functionalized silicon nanocrystals and their application to cancer cell imaging. Journal of Materials Chemistry. B, Materials for Biology and Medicine, 2014, 2(47): 8427–8433
Lai C H, Hütter J, Hsu C W, Tanaka H, Varela-Aramburu S, De Cola L, Lepenies B, Seeberger P H. Analysis of carbohydratecarbohydrate interactions using sugar-functionalized silicon nanoparticles for cell imaging. Nano Letters, 2016, 16(1): 807–811
Hsu C W, Septiadi D, Lai C H, Chen P K, Seeberger P H, De Cola L. Glucose-modified silicon nanoparticles for cellular imaging. ChemPlusChem, 2017, 82(4): 660–667
Cheng F F, Liang G X, Shen Y Y, Rana R K, Zhu J J. N-Acetylglucosamine biofunctionalized CdSeTe quantum dots as fluorescence probe for specific protein recognition. Analyst (London), 2013, 138(2): 666–670
Ahire J H, Chambrier I, Mueller A, Bao Y, Chao Y. Synthesis of Dmannose capped silicon nanoparticles and their interactions with MCF-7 human breast cancerous cells. ACS Applied Materials & Interfaces, 2013, 5(15): 7384–7391
Ahire J H, Behray M, Webster C A, Wang Q, Sherwood V, Saengkrit N, Ruktanonchai U, Woramongkolchai N, Chao Y. Synthesis of carbohydrate capped silicon nanoparticles and their reduced cytotoxicity, in vivo toxicity, and cellular uptake. Advanced Healthcare Materials, 2015, 4(12): 1877–1886
Dalal C, Jana N R. Galactose multivalency effect on the cell uptake mechanism of bioconjugated nanoparticles. Journal of Physical Chemistry C, 2018, 122(44): 25651–25660
Zayed D G, Ebrahim S M, Helmy MW, Khattab S N, Bahey-El-Din M, Fang J Y, Elkhodairy K A, Elzoghby A O. Combining hydrophilic chemotherapy and hydrophobic phytotherapy via tumor-targeted albumin-QDs nano-hybrids: Covalent coupling and phospholipid complexation approaches. Journal of Nanobiotechnology, 2019, 17(1): 19
Yin C, Ying L, Zhang P C, Zhuo R X, Kang E T, Leong K W, Mao H Q. High density of immobilized galactose ligand enhances hepatocyte attachment and function. Journal of Biomedical Materials Research. Part A, 2003, 67A(4): 1093–1104
Hata S, Ishii K. Effect of galactose on binding and endocytosis of asiaioglycoprotein in cultured rat hepatocytes. Annals of Nuclear Medicine, 1998, 12(5): 255–259
Mishra N, Yadav N P, Rai V K, Sinha P, Yadav K S, Jain S, Arora S. Efficient hepatic delivery of drugs: Novel strategies and their significance. BioMed Research International, 2013, 2013: 20
Yousef S, Alsaab H O, Sau S, Iyer A K. Development of asialoglycoprotein receptor directed nanoparticles for selective delivery of curcumin derivative to hepatocellular carcinoma. Heliyon, 2018, 4(12): e01071
Pranatharthiharan S, Patel M D, Malshe V C, Pujari V, Gorakshakar A, Madkaikar M, Ghosh K, Devarajan P V. Asialoglycoprotein receptor targeted delivery of doxorubicin nanoparticles for hepatocellular carcinoma. Drug Delivery, 2017, 24(1): 20–29
Abe M, Manola J B, OhWK, Parslow D L, George D J, Austin C L, Kantoff P W. Plasma levels of heat shock protein 70 in patients with prostate cancer: A potential biomarker for prostate cancer. Clinical Prostate Cancer, 2004, 3(1): 49–53
Ciocca D R, Calderwood S K. Heat shock proteins in cancer: Diagnostic, prognostic, predictive, and treatment implications. Cell Stress & Chaperones, 2005, 10(2): 86–103
Garrido C, Brunet M, Didelot C, Zermati Y, Schmitt E, Kroemer G. Heat shock proteins 27 and 70: Anti-apoptotic proteins with tumorigenic properties. Cell Cycle (Georgetown, Tex.), 2006, 5(22): 2592–2601
Ahire J H, Wang Q, Coxon P R, Malhotra G, Brydson R, Chen R, Chao Y. Highly luminescent and nontoxic amine-capped nanoparticles from porous silicon: Synthesis and their use in biomedical imaging. ACS Applied Materials & Interfaces, 2012, 4(6): 3285–3292
Zhang L W, Monteiro-Riviere N A. Mechanisms of quantum dot nanoparticle cellular uptake. Toxicological Sciences, 2009, 110(1): 138–155
Yuan F L, Li S H, Fan Z T, Meng X Y, Fan L Z, Yang S H. Shining carbon dots: Synthesis and biomedical and optoelectronic applications. Nano Today, 2016, 11(5): 565–586
Zhang M, Bai L L, Shang W H, Xie W J, Ma H, Fu Y Y, Fang D C, Sun H, Fan L Z, Han M, et al. Facile synthesis of water-soluble, highly fluorescent graphene quantum dots as a robust biological label for stem cells. Journal of Materials Chemistry, 2012, 22(15): 7461–7467
Fan Z T, Zhou S X, Garcia C, Fan L Z, Zhou J B. pH-responsive fluorescent graphene quantum dots for fluorescence-guided cancer surgery and diagnosis. Nanoscale, 2017, 9(15): 4928–4933
Wang Q, Bao Y, Zhang X, Coxon P R, Jayasooriya U A, Chao Y. Uptake and toxicity studies of poly-acrylic acid functionalized silicon nanoparticles in cultured mammalian cells. Advanced Healthcare Materials, 2012, 1(2): 189–198
Park J H, Gu L, von Maltzahn G, Ruoslahti E, Bhatia S N, Sailor M J. Biodegradable luminescent porous silicon nanoparticles for in vivo applications. Nature Materials, 2009, 8(4): 331–336
Chen H, Cui S, Tu Z, Gu Y, Chi X. In vivo monitoring of organ-selective distribution of cdhgte/SiO2 nanoparticles in mouse model. Journal of Fluorescence, 2012, 22(2): 699–706
Qu Y, Li W, Zhou Y, Liu X, Zhang L,Wang L, Li Y F, Iida A, Tang Z, Zhao Y, et al. Full assessment of fate and physiological behavior of quantum dots utilizing caenorhabditis elegans as a model organism. Nano Letters, 2011, 11(8): 3174–3183
Schipper M L, Iyer G, Koh A L, Cheng Z, Ebenstein Y, Aharoni A, Keren S, Bentolila L A, Li J, Rao J, et al. Particle size, surface coating, and pegylation influence the biodistribution of quantum dots in living mice. Small, 2009, 5(1): 126–134
Choi HS, Liu W, Misra P, Tanaka E, Zimmer J P, Ipe B I, Bawendi M G, Frangioni J V. Renal clearance of quantum dots. Nature Biotechnology, 2007, 25(10): 1165–1170
Zhu Y, Hong H, Xu Z P, Li Z, Cai W. Quantum dot-based nanoprobes for in vivo targeted imaging. Current Molecular Medicine, 2013, 13(10): 1549–1567
Vela-Ramirez J E, Goodman J T, Boggiatto P M, Roychoudhury R, Pohl N L B, Hostetter J M, Wannemuehler M J, Narasimhan B. Safety and biocompatibility of carbohydrate-functionalized polyanhydride nanoparticles. AAPS Journal, 2015, 17(1): 256–267
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Ashree, J., Wang, Q. & Chao, Y. Glyco-functionalised quantum dots and their progress in cancer diagnosis and treatment. Front. Chem. Sci. Eng. 14, 365–377 (2020). https://doi.org/10.1007/s11705-019-1863-7
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DOI: https://doi.org/10.1007/s11705-019-1863-7
Keywords
- carbohydrate
- leptin
- glyco-functionalised QD
- bioimaging
- cancer diagnosis and treatment