PHARMACEUTICAL AND BIOPHARMACEUTICAL ASPECTS OF QUANTUM DOTS-AN OVERVIEW

SADDAM C. SHAIKH; SHWETA G. SABOO; PRASHANT S. TANDALE; FAHIM S. MEMON; SHARAD D. TAYADE; M. AKIFUL HAQUE; SHARUK L. KHAN

doi:10.22159/ijap.2021v13i5.41623

Authors

SADDAM C. SHAIKH Department of Pharmaceutics (D Pharm), Rajarshi Shahu College of Pharmacy, Buldana, Maharashtra, India 443001,
SHWETA G. SABOO Department of Pharmacognosy, Government College of Pharmacy, Karad, Maharashtra, India 415124
PRASHANT S. TANDALE Department of Pharmaceutics, School of Pharmaceutical Sciences, Lovely Professional University, Punjab, India 144001
FAHIM S. MEMON Department of Pharmaceutics, Rajarshi Shahu College of Pharmacy, Buldana, Maharashtra, India-443001
SHARAD D. TAYADE Department of Pharmaceutics (D Pharm), Rajarshi Shahu College of Pharmacy, Buldana, Maharashtra, India 443001
M. AKIFUL HAQUE Department of Pharmaceutical Analysis, Anurag University, Venkatapur, Hyderabad, India 500088
SHARUK L. KHAN Department of Pharmaceutical Chemistry, MUP's College of Pharmacy (B Pharm), Degaon, Risod, Washim, Maharashtra, India 444504

DOI:

https://doi.org/10.22159/ijap.2021v13i5.41623

Keywords:

Quantum dots, Optical properties, Microwave-assisted method, Cytotoxicity, Cell imaging, Sentinel lymph-node mapping

Abstract

In the twenty-first century, nanotechnology has become cutting-edge technology. It is interdisciplinary and multidisciplinary, covering numerous fields such as medicine, engineering, biology, physics, material sciences, and chemistry. The present work aims to cover the optical properties, method of preparations, surface modifications, bio-conjugation, characterization, stability, and cytotoxicity of quantum dots (QDs).

Articles were reviewed in English literature reporting the pharmaceutical and bio-pharmaceutical aspects of QDs which were indexed in Scopus, web of science, google scholar and PubMed without applying the year of publication criterion.

One significant value of utilizing nanotechnology is that one can alter and control the properties in a genuinely unsurprising way to address explicit applications' issues. In science and biomedicine, the usage of functional nanomaterials has been broadly investigated and has become one of the quick-moving and stimulating research directions. Different types of nanomaterial (silicon nanowires, QDs, carbon nanotubes, nanoparticles of gold/silver) were extensively utilized for biological purposes. Nanomedicine shows numerous advantages in the natural characteristics of targeted drug delivery and therapeutics. For instance, protection of drugs against degradation, improvement in the drug's stability, prolonged circulation time, deceased side effects, and enhanced distribution in tissues. The present review article deals with the quantum dots, their optical properties, method of preparations, surface modifications, bio-conjugation, characterization, stability, and cytotoxicity of quantum dots. The review also discusses various biomedical applications of QDs.

The QDs-based bio-nanotechnology will always be in the growing list of unique applications, with progress being made in specialized nanoparticle development, the detection of elegant conjugation methods, and the discovery of new targeting ligands.

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References

Matea CT, Mocan T, Tabaran F, Pop T, Mosteanu O, Puia C, et al. Quantum dots in imaging, drug delivery and sensor applications. Int J Nanomed 2017;12:5421–31.

Moreels I, Justo Y, Geyter B De, Haustraete K, Martins JC, Hens Z. Quantum dots: a surface chemistry study. ACS Nano 2012;5:2004–12.

Dabbousi BO, Rodriguez Viejo J, Mikulec FV, Heine JR, Mattoussi H, Ober R, et al. (CdSe)ZnS core-shell quantum dots: synthesis and characterization of a size series of highly luminescent nanocrystallites. J Phys Chem B 1997;101:9463–75.

Maxwell T, Nogueira Campos MG, Smith S, Doomra M, Thwin Z, Santra S. Quantum dots. In: Nanoparticles for biomedical applications: fundamental concepts, biological interactions and clinical applications; 2019. p. 243–65.

Senthil Kumar M, Valarmathi S, Bhima P, Prudhvi Devabaktuni S, Raja A, Vallabhaneni SD. Quantum dots. Int J Pharm Technol 2012;4:1929–49.

Bawendi MG, Steigerwald ML, Brus LE. The quantum mechanics of larger semiconductor clusters (“Quantum dots”). Annu Rev Phys Chem 1990;41:477–96.

Biju V. Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy. Chem Soc Rev 2014;43:744–64.

Portney NG, Ozkan M. Nano-oncology: drug delivery, imaging, and sensing. Anal Bioanal Chem 2006;384:620–30.

Godbole NN, Galgatte UC, Chaudhari PD. Development and in vitro evaluation of quantum dots as a carrier for delivery of 5-fluorouracil. Int J Pharm Pharm Sci 2016;8:289–96.

SLJ, Gupta NV. Diabetic retinopathy: an inclusive review on current treatment and management approaches. Asian J Pharm Clin Res 2018;11:54.

Qi L, Gao X. Emerging application of quantum dots for drug delivery and therapy. Expert Opinion Drug Delivery 2008;5:263–7.

Zrazhevskiy P, Sena M, Gao X. Designing multifunctional quantum dots for bioimaging, detection, and drug delivery. Chem Soc Rev 2010;39:4326–54.

Maysinger D, Lovric J, Eisenberg A, Savic R. Fate of micelles and quantum dots in cells. Eur J Pharm Biopharm 2007;65:270–81.

Caruthers SD, Wickline SA, Lanza GM. Nanotechnological applications in medicine. Curr Opinion Biotechnol 2007;18:26–30.

Wagner AM, Knipe JM, Orive G, Peppas NA. Quantum dots in biomedical applications. Acta Biomaterialia 2019;94:44–63.

Kong FY, Zhang JW, Li RF, Wang ZX, Wang WJ, Wang W. Unique roles of gold nanoparticles in drug delivery, targeting and imaging applications. Molecules 2017;22:1445.

Wang Q, Huang X, Long Y, Wang X, Zhang H, Zhu R, et al. Hollow luminescent carbon dots for drug delivery. Carbon 2013;59:192–9.

Wegner KD, Hildebrandt N. Quantum dots: Bright and versatile in vitro and in vivo fluorescence imaging biosensors. Chem Soc Rev 2015;44:4792–834.

Lee JH, Yigit MV, Mazumdar D, Lu Y. Molecular diagnostic and drug delivery agents based on aptamer-nanomaterial conjugates. Adv Drug Delivery Rev 2010;62:592–605.

Xu G, Zeng S, Zhang B, Swihart MT, Yong KT, Prasad PN. New generation cadmium-free quantum dots for biophotonics and nanomedicine. Chem Rev 2016;116:12234–327.

Chinnathambi S, Chen S, Ganesan S, Hanagata N. Silicon quantum dots for biological applications. Adv Healthcare Mater 2014;3:10–29.

Probst CE, Zrazhevskiy P, Bagalkot V, Gao X. Quantum dots as a platform for nanoparticle drug delivery vehicle design. Adv Drug Delivery Rev 2013;65:703–18.

Frecker T, Bailey D, Arzeta Ferrer X, McBride J, Rosenthal SJ. Review-quantum dots and their application in lighting, displays, and biology. ECS J Solid State Sci Technol 2016;5:R3019–31.

Lin J, Chen X, Huang P. Graphene-based nanomaterials for bioimaging. Adv Drug Delivery Rev 2016;105:242–54.

Ramamurthy SK, Sridhar C. Parthenium mediated synthesis of zinc oxide nanoparticles and its characterization. Int J Appl Pharm 2019;11:113–6.

Sivapriya V, Ponnarmadha S, Azeezand NA, Sudarshanadeepa V. Novel nanocarriers for ethnopharmacological formulations. Int J Appl Pharm 2018;10:26–30.

Jinhao GAO, Hongwei GU, Bing XU. Multifunctional magnetic nanoparticles: design, synthesis, and biomedical applications. Acc Chem Res 2009;42:1097–107.

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.

Martinez Carmona M, Gun’Ko Y, Vallet Regi M. Zno nanostructures for drug delivery and theranostic applications. Nanomaterials 2018;8:268.

Boakye Yiadom KO, Kesse S, Opoku Damoah Y, Filli MS, Aquib M, Joelle MMB, et al. Carbon dots: applications in bioimaging and theranostics. Int J Pharm 2019;564:308–17.

Liu ML, Chen B Bin, Li CM, Huang CZ. Carbon dots: synthesis, formation mechanism, fluorescence origin and sensing applications. Green Chem 2019;21:449–71.

Delehanty JB, Mattoussi H, Medintz IL. Delivering quantum dots into cells: Strategies, progress and remaining issues. Anal Bioanal Chem 2009;393:1091–105.

Bilan R, Fleury F, Nabiev I, Sukhanova A. Quantum dot surface chemistry and functionalization for cell targeting and imaging. Bioconjugate Chem 2015;26:609–24.

Hild WA, Breunig M, Goepferich A. Quantum dots-nano-sized probes for the exploration of cellular and intracellular targeting. Eur J Pharm Biopharm 2008;68:153–68.

Bulte JWM, Modo MMJ. Design and applications of nanoparticles in biomedical imaging. Design and applications of nanoparticles in biomedical imaging; 2016. p. 1–469.

Azzazy HME, Mansour MMH, Kazmierczak SC. From diagnostics to therapy: prospects of quantum dots. Clin Biochem 2007;40:917–27.

Massey M, Wu M, Conroy EM, Algar WR. Mind your P’s and Q’s: the coming of age of semiconducting polymer dots and semiconductor quantum dots in biological applications. Curr Opinion Biotechnol 2015;34:30–40.

Jaleel JA, Pramod K. Artful and multifaceted applications of carbon dot in biomedicine. J Controlled Release 2018;269:302–21.

Gittard SD, Miller PR, Boehm RD, Ovsianikov A, Chichkov BN, Heiser J, et al. Multiphoton microscopy of transdermal quantum dot delivery using two-photon polymerization-fabricated polymer microneedles. Faraday Discuss 2011;149:171–85.

Zuo P, Lu X, Sun Z, Guo Y, He H. A review on syntheses, properties, characterization and bioanalytical applications of fluorescent carbon dots. Microchim Acta 2016;183:519–42.

Ding C, Zhu A, Tian Y. Functional surface engineering of C-dots for fluorescent biosensing and in vivo bioimaging. Acc Chem Res 2014;47:20–30.

Homan K, Mallidi S, Cooley E, Emelianov S. Combined photoacoustic and ultrasound imaging of metal nanoparticles in vivo. Nanoimaging 2011;3:225–49.

Gao X, Du C, Zhuang Z, Chen W. Carbon quantum dot-based nanoprobes for metal ion detection. J Materials Chem C 2016;4:6927–45.

Geszke Moritz M, Moritz M. Quantum dots as versatile probes in medical sciences: synthesis, modification and properties. Mater Sci Eng 2013;33:1008–21.

Molaei MJ. A review on nanostructured carbon quantum dots and their applications in biotechnology, sensors, and chemiluminescence. Talanta 2019;196:456–78.

Bajwa N, Mehra NK, Jain K, Jain NK. Pharmaceutical and biomedical applications of quantum dots. Artif Cells Nanomed Biotechnol 2016;44:758–68.

Dey N, Rao M. Quantum dot: novel carrier for drug delivery. Int J Res Pharm Biomed Sci 2011;2:448–58.

Mo D, Hu L, Zeng G, Chen G, Wan J, Yu Z, et al. Cadmium-containing quantum dots: properties, applications, and toxicity. Appl Microbiol Biotechnol 2017;101:2713–33.

Nakahara M, Ohmi T. Quantum computing with quantum dots. In: Quantum Computing; 2008. p. 377–98.

Wu P, Yan XP. Doped quantum dots for chemo/biosensing and bioimaging. Chem Soc Rev 2013;42:5489–521.

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.

Gaponik N, Talapin DV, Rogach AL, Hoppe K, Shevchenko EV, Kornowski A, et al. Thiol-capping of CDTe nanocrystals: An alternative to organometallic synthetic routes. J Phys Chem B 2002;106:7177–85.

Emin S, Singh SP, Han L, Satoh N, Islam A. Colloidal quantum dot solar cells. Sol Energy 2011;85:1264–82.

Chen W, Lv G, Hu W, Li D, Chen S, Dai Z. Synthesis and applications of graphene quantum dots: a review. Nanotechnol Rev 2018;7:157–85.

Campuzano S, Yanez Sedeno P, Pingarron JM. Carbon dots and graphene quantum dots in electrochemical biosensing. Nanomaterials 2019;9:634.

Lim SY, Shen W, Gao Z. Carbon quantum dots and their applications. Chem Soc Rev 2015;44:362–81.

Barroso MM. Quantum dots in cell biology. J Histochem Cytochem 2011;59:237–51.

Klimov VI, Mikhailovsky AA, Xu S, Malko A, Hollingsworth JA, Leatherdale CA, et al. Optical gain and stimulated emission in nanocrystal quantum dots. Science 2000;290:314–7.

Kim S, Fisher B, Eisler HJ, Bawendi M. Type-II quantum dots: CdTe/CdSe(core/shell) and CdSe/ZnTe(core/shell) heterostructures. J Am Chem Soc 2003;125:11466–7.

Chan WCW, Maxwell DJ, Gao X, Bailey RE, Han M, Nie S. Luminescent quantum dots for multiplexed biological detection and imaging. Curr Opinion Biotechnol 2002;13:40–6.

True LD, Gao X. Quantum dots for molecular pathology: their time has arrived. J Mol Diagnostics 2007;9:7–11.

Moloney MP, Govan J, Loudon A, Mukhina M, Gun’ko YK. Preparation of chiral quantum dots. Nat Protoc 2015;10:558–73.

Ghaderi S, Ramesh B, Seifalian AM. Fluorescence nanoparticles “quantum dots” as drug delivery system and their toxicity: a review. J Drug Targeting 2011;19:475–86.

Nurunnabi M, Parvez K, Nafiujjaman M, Revuri V, Khan HA, Feng X, et al. Bioapplication of graphene oxide derivatives: drug/gene delivery, imaging, polymeric modification, toxicology, therapeutics and challenges. RSC Adv 2015;5:42141–61.

Obonyo O, Fisher E, Edwards M, Douroumis D. Quantum dots synthesis and biological applications as imaging and drug delivery systems. Crit Rev Biotechnol 2010;30:283–301.

Bilan R, Nabiev I, Sukhanova A. Quantum dot-based nanotools for bioimaging, diagnostics, and drug delivery. Chem BioChem 2016;17:2103–14.

Gulia S, Kakkar R. Zno quantum dots for biomedical applications. Adv Materials Lett 2013;4:876–87.

Liu X, Pang J, Xu F, Zhang X. Simple approach to synthesize amino-functionalized carbon dots by carbonization of chitosan. Sci Rep 2016;6:31100.

Coe S, Woo WK, Bawendi M, Bulovic V. Electroluminescence from single monolayers of nanocrystals in molecular organic devices. Nature 2002;420:800–3.

Swarnkar A, Marshall AR, Sanehira EM, Chernomordik BD, Moore DT, Christians JA, et al. Quantum dot-induced phase stabilization of α-CsPbI3 perovskite for high-efficiency photovoltaics. Science 2016;354:92–5.

Bak S, Kim D, Lee H. Graphene quantum dots and their possible energy applications: a review. Curr Appl Physics 2016;16:1192–201.

Grisorio R, Debellis D, Suranna GP, Gigli G, Giansante C. The dynamic organic/inorganic interface of colloidal PbS quantum dots. Angew Chem Int Ed 2016;55:6628–33.

Seguin R, Schliwa A, Rodt S, Potschke K, Pohl UW, Bimberg D. Size-dependent fine-structure splitting in self-organized InAs/GaAs quantum dots. Phys Rev Lett 2005;95:257402.

Bhattacharya P, Ghosh S, Stiff Roberts AD. Quantum dot opto-electronic devices. Annu Rev Mater Res 2004;34:1–40.

Li H, He X, Kang Z, Huang H, Liu Y, Liu J, et al. Water-soluble fluorescent carbon quantum dots and photocatalyst design. Angew Chem Int Ed 2010;49:4430–4.

Darbandi M, Thomann R, Nann T. Single quantum dots in silica spheres by microemulsion synthesis. Chem Mater 2005;17:5720–5.

Tang L, Ji R, Cao X, Lin J, Jiang H, Li X, et al. Deep ultraviolet photoluminescence of water-soluble self-passivated graphene quantum dots. ACS Nano 2012;6:5102–10.

Wang F, Pang S, Wang L, Li Q, Kreiter M, Liu CY. One-step synthesis of highly luminescent carbon dots in noncoordinating solvents. Chem Mater 2010;22:4528–30.

Ahirwar S, Mallick S, Bahadur D. Electrochemical method to prepare graphene quantum dots and graphene oxide quantum dots. ACS Omega 2017;2:8343–53.

Nann T. Phase-transfer of CdSe@ZnS quantum dots using amphiphilic hyperbranched polyethyleneimine. Chem Commun 2005;13:1735–6.

Tian P, Tang L, Teng KS, Lau SP. Graphene quantum dots from chemistry to applications. Materials Today Chem 2018;10:221–58.

Baruah S, Dutta J. Hydrothermal growth of ZnO nanostructures. Sci Technol Adv Mater 2009;10:013001.

Wang Q, Zheng H, Long Y, Zhang L, Gao M, Bai W. Microwave-hydrothermal synthesis of fluorescent carbon dots from graphite oxide. Carbon NY 2011;49:3134–40.

Prasannan A, Imae T. One-pot synthesis of fluorescent carbon dots from orange waste peels. Ind Eng Chem Res 2013;52:15673–8.

Park SY, Thongsai N, Chae A, Jo S, Kang EB, Paoprasert P, et al. Microwave-assisted synthesis of luminescent and biocompatible lysine-based carbon quantum dots. J Ind Eng Chem 2017;47:329–35.

He Y, Zhong Y, Peng F, Wei X, Su Y, Lu Y, et al. One-pot microwave synthesis of water-dispersible, ultraphoto-and pH-stable, and highly fluorescent silicon quantum dots. J Am Chem Soc 2011;133:14192–5.

Sumanth Kumar D, Jai Kumar B, Mahesh HM. Quantum nanostructures (QDs): an overview. In: Synthesis of Inorganic Nanomaterials; 2018. p. 59–88.

Liu Y, Xiao N, Gong N, Wang H, Shi X, Gu W, et al. One-step microwave-assisted polyol synthesis of green luminescent carbon dots as optical nanoprobes. Carbon 2014;68:258–64.

Singh I, Arora R, Dhiman H, Pahwa R. Carbon quantum dots: Synthesis, characterization and biomedical applications. Turkish J Pharm Sci 2018;15:219–30.

Wang X, Feng Y, Dong P, Huang J. A mini-review on carbon quantum dots: preparation, properties, and electrocatalytic application. Front Chem 2019;7:671.

Qian H, Qiu X, Li L, Ren J. Microwave-assisted aqueous synthesis: A rapid approach to prepare highly luminescent ZnSe(S) alloyed quantum dots. J Phys Chem B 2006;110:9034–40.

Rangel Mendez JR, Matos J, Chazaro Ruiz LF, Gonzalez Castillo AC, Barrios Yanez G. Microwave-assisted synthesis of C-doped TiO 2 and ZnO hybrid nanostructured materials as quantum-dots sensitized solar cells. Appl Surf Sci 2018;434:744–55.

Lehnen T, Zopes D, Mathur S. Phase-selective microwave synthesis and inkjet printing applications of Zn 2SnO 4 (ZTO) quantum dots. J Mater Chem 2012;22:17732–6.

Vasudevan D, Gaddam RR, Trinchi A, Cole I. Core-shell quantum dots: properties and applications. J Alloys Compounds 2015;636:395–404.

Wu YL, Lim CS, Fu S, Tok AIY, Lau HM, Boey FYC, et al. Surface modifications of ZnO quantum dots for bio-imaging. Nanotechnology 2007;18:215604.

Monopoli MP, Pitek AS, Lynch I, Dawson KA. Nanomaterial interfaces in biology. In: Nanomaterial Interfaces in Biology: Methods and Protocols, Methods in Molecular Biology; 2013;1025:137155.

Yuan CT, Chou WC, Chuu DS, Chang WH, Lin HS, Ruaan RC. Fluorescence properties of colloidal CdSe/ZnS quantum dots with various surface modifications. J Med Biol Eng 2006;26:131–5.

Krogmeier JR, Kang HG, Clarke ML, Yim P, Hwang J. Probing the dynamic fluorescence properties of single water-soluble quantum dots. Opt Commun 2008;281:1781–8.

Kumar P, Kukkar D, Deep A, Sharma SC, Bharadwaj LM. Synthesis of mercaptopropionic acid stabilized CDS quantum dots for bioimaging in breast cancer. Adv Mater Lett 2012;3:471–5.

Borse V, Sadawana M, Srivastava R. CdTe quantum dots: aqueous phase synthesis, stability studies and protein conjugation for development of biosensors. In: Nanophotonics VI; 2016;9884:988423.

Singla R, Guliani A, Kumari A, Yadav SK. Metallic nanoparticles, toxicity issues and applications in medicine. In: Nanoscale materials in targeted drug delivery, theragnosis and tissue regeneration; 2016. p. 41–80.

Dobhal G, Garima. Quantum dot bioconjugates for the detection of extracellular vesicles in saliva and breath. MSc Thesis; 2019. Available from http://researcharchive.vuw.ac.nz/handle/ 10063/8119. [Last accessed on 10 Mar 2021].

Tian B, Al-Jamal WT, Stuart M, Kostarelos K. Doxorubicin-loaded and antibody-conjugated liposome-QD hybrid vesicles for targeted cancer therapy and imaging. In: Nanotechnology 2010: Bio Sensors, Instruments, Medical, Environment and Energy-Technical Proceedings of the 2010 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2010; 3:380–1.

Pardo J, Peng Z, Leblanc RM. Cancer targeting and drug delivery using carbon-based quantum dots and nanotubes. Molecules 2018;23:378.

Howarth M, Takao K, Hayashi Y, Ting AY. Targeting quantum dots to surface proteins in living cells with biotin ligase. Proc Natl Acad Sci USA 2005;102:7583–8.

Liu W, Howarth M, Greytak AB, Zheng Y, Nocera DG, Ting AY, et al. Compact biocompatible quantum dots functionalized for cellular imaging. J Am Chem Soc 2008;130:1274–84.

Smith AM, Duan H, Mohs AM, Nie S. Bioconjugated quantum dots for in vivo molecular and cellular imaging. Adv Drug Delivery Rev 2008;60:1226–40.

Ghasemi Y, Peymani P, Afifi S. Quantum dot: magic nanoparticle for imaging, detection and targeting. Acta Biomed l’Ateneo Parm 2009;80:156–65.

Kim D, Kim DH, Lee JH, Grossman JC. Impact of stoichiometry on the electronic structure of PbS quantum dots. Phys Rev Lett 2013;110:196802.

Rhyner MN, Smith AM, Goo X, Mao H, Yang L, Nie S. Quantum dots and multifunctional nanoparticles: new contrast agents for tumor imaging. Nanomedicine 2006;1:209–17.

Liu W, Hak SC, Zimmer JP, Tanaka E, Frangioni JV, Bawendi M. Compact cysteine-coated CdSe(ZnCdS) quantum dots for in vivo applications. J Am Chem Soc 2007;129:14530–1.

Liu DS, Phipps WS, Loh KH, Howarth M, Ting AY. Quantum dot targeting with lipoic acid ligase and HaloTag for single-molecule imaging on living cells. ACS Nano 2012;6:11080–7.

Drbohlavova J, Adam V, Kizek R, Hubalek J. Quantum dots-characterization, preparation and usage in biological systems. Int J Mol Sci 2009;10:656–73.

Murray CB, Kagan CR, Bawendi MG. Self-organization of CdSe nanocrystallites into three-dimensional quantum dot superlattices. Science 1995;270:1335–8.

Micic OI, Curtis CJ, Jones KM, Sprague JR, Nozik AJ. Synthesis and characterization of InP quantum dots. J Phys Chem 1994;98:4966–9.

Lipovskii A, Kolobkova E, Petrikov V, Kang I, Olkhovets A, Krauss T, et al. Synthesis and characterization of PbSe quantum dots in phosphate glass. Appl Phys Lett 1997;71:3406–8.

Knittel F, Gravel E, Cassette E, Pons T, Pillon F, Dubertret B, et al. On the characterization of the surface chemistry of quantum dots. Nano Lett 2013;13:5075–8.

Micic OI, Sprague JR, Curtis CJ, Jones KM, Machol JL, Nozik AJ, et al. Synthesis and characterization of InP, GaP, and GaInP2 quantum dots. J Phys Chem 1995;99:7754–9.

Passaseo A. Quantum dots: introduction. Science 2010;4:1–25.

Derfus AM, Chan WCW, Bhatia SN. Probing the cytotoxicity of semiconductor quantum dots. Nano Lett 2004;4:11–8.

Hoshino A, Fujioka K, Oku T, Suga M, Sasaki YF, Ohta T, et al. Physicochemical properties and cellular toxicity of nanocrystal quantum dots depend on their surface modification. Nano Lett 2004;4:2163–9.

Zhao F, Zhao Y, Liu Y, Chang X, Chen C, Zhao Y. Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small 2011;7:1322–37.

Su Y, Hu M, Fan C, He Y, Li Q, Li W, et al. The cytotoxicity of CdTe quantum dots and the relative contributions from released cadmium ions and nanoparticle properties. Biomaterials 2010;31:4829–34.

Chong Y, Ma Y, Shen H, Tu X, Zhou X, Xu J, et al. The in vitro and in vivo toxicity of graphene quantum dots. Biomaterials 2014;35:5041–8.

Tsay JM, Michalet X. New light on quantum dot cytotoxicity. Chem Biol 2005;12:1159–61.

Wu C, Wang C, Han T, Zhou X, Guo S, Zhang J. Insight into the cellular internalization and cytotoxicity of graphene quantum dots. Adv Healthc Mater 2013;2:1613–9.

Guo G, Liu W, Liang J, He Z, Xu H, Yang X. Probing the cytotoxicity of CdSe quantum dots with surface modification. Mater Lett 2007;61:1641–4.

Tan YF, Chandrasekharan P, Maity D, Yong CX, Chuang KH, Zhao Y, et al. Multimodal tumor imaging by iron oxides and quantum dots formulated in poly (lactic acid)-d-alpha-tocopheryl polyethylene glycol 1000 succinate nanoparticles. Biomaterials 2011;32:2969–78.

Liu Y, Ai K, Yuan Q, Lu L. Fluorescence-enhanced gadolinium-doped zinc oxide quantum dots for magnetic resonance and fluorescence imaging. Biomaterials 2011;32:1185–92.

Chen Y, Chen Z, He Y, Lin H, Sheng P, Liu C, et al. L-cysteine-capped CdTe QD-based sensor for simple and selective detection of trinitrotoluene. Nanotechnology 2010;21:125502.

Juzenas P, Chen W, Sun YP, Coelho MAN, Generalov R, Generalova N, et al. Quantum dots and nanoparticles for photodynamic and radiation therapies of cancer. Adv Drug Delivery Rev 2008;60:1600–14.

Han M, Gao X, Su JZ, Nie S. Quantum-dot-tagged microbeads for multiplexed optical coding of biomolecules. Nat Biotechnol 2001;19:631–5.

Lagerholm BC, Wang M, Ernst LA, Ly DH, Liu H, Bruchez MP, et al. Multicolor coding of cells with cationic peptide coated quantum dots. Nano Lett 2004;4:2019–22.

Li J, Zhao XW, Zhao YJ, Gu ZZ. Quantum-dot-coated encoded silica colloidal crystals beads for multiplex coding. Chem Commun 2009;17:2329–31.

Tholouli E, Sweeney E, Barrow E, Clay V, Hoyland JA, Byers RJ. Quantum dots light up pathology. J Pathol 2008;216:275–85.

Xia Z, Xing Y, So MK, Koh AL, Sinclair R, Rao J. Multiplex detection of protease activity with quantum dot nanosensors prepared by intein-mediated specific bioconjugation. Anal Chem 2008;80:8649–55.

Zheng XT, Ananthanarayanan A, Luo KQ, Chen P. Glowing graphene quantum dots and carbon dots: properties, syntheses, and biological applications. Small 2015;11:1620–36.

Bourlinos AB, Stassinopoulos A, Anglos D, Zboril R, Karakassides M, Giannelis EP. Surface functionalized carbogenic quantum dots. Small 2008;4:455–8.

Kagan CR, Murray CB, Nirmal M, Bawendi MG. Electronic energy transfer in CdSe quantum dot solids. Phys Rev Lett 1996;76:1517–20.

Valizadeh A, Mikaeili H, Samiei M, Farkhani SM, Zarghami N, Kouhi M, et al. Quantum dots: synthesis, bioapplications, and toxicity. Nanoscale Res Lett 2012;7:480.

Luo PG, Sahu S, Yang ST, Sonkar SK, Wang J, Wang H, et al. Carbon “quantum” dots for optical bioimaging. J Mater Chem B 2013;1:2116–27.

Bakker MA, Mehl S, Hiltunen T, Harju A, Divincenzo DP. Validity of the single-particle description and charge noise resilience for multielectron quantum dots. Phys Rev B-Condens Matter Mater Phys 2015;91:155425.

Choi YE, Kwak JW, Park JW. Nanotechnology for early cancer detection. Sensors 2010;10:428–55.

Walling MA, Novak JA, Shepard JRE. Quantum dots for live cell and in vivo imaging. Int J Mol Sci 2009;10:441–91.

Qian ZS, Shan XY, Chai LJ, Ma JJ, Chen JR, Feng H. DNA nanosensor based on biocompatible graphene quantum dots and carbon nanotubes. Biosens Bioelectron 2014;60:64–70.

Obliosca JM, Liu C, Batson RA, Babin MC, Werner JH, Yeh HC. DNA/RNA detection using DNA-templated few-atom silver nanoclusters. Biosensors 2013;3:185–200.

Su S, Fan J, Xue B, Yuwen L, Liu X, Pan D, et al. DNA-conjugated quantum dot nanoprobe for high-sensitivity fluorescent detection of DNA and micro-RNA. ACS Appl Mater Interfaces 2014;6:1152-7.

Tikhomirov G, Hoogland S, Lee PE, Fischer A, Sargent EH, Kelley SO. DNA-based programming of quantum dot valency, self-assembly and luminescence. Nat Nanotechnol 2011;6:485–90.

Kim SS, Ye C, Kumar P, Chiu I, Subramanya S, Wu H, et al. Targeted delivery of sirna to macrophages for anti-inflammatory treatment. Mol Ther 2010;18:993–1001.

Bonoiu A, Mahajan SD, Ye L, Kumar R, Ding H, Yong KT, et al. MMP-9 gene silencing by a quantum dot-siRNA nanoplex delivery to maintain the integrity of the blood brain barrier. Brain Res 2009;1282:142–55.

Bruun J, Larsen TB, Jølck RI, Eliasen R, Holm R, Gjetting T, et al. Investigation of enzyme-sensitive lipid nanoparticles for delivery of siRNA to blood-brain barrier and glioma cells. Int J Nanomed 2015;10:5995–6008.

Lin G, Chen T, Zou J, Wang Y, Wang X, Li J, et al. Quantum dots-siRNA nanoplexes for gene silencing in central nervous system tumor cells. Front Pharmacol 2017;8:182.

Djikanovic D, Kalauzi A, Jeremic M, Xu J, Micic M, Whyte JD, et al. Interaction of the CdSe quantum dots with plant cell walls. Colloids Surf B 2012;91:41–7.

Wang J, Yang Y, Zhu H, Braam J, Schnoor JL, Alvarez PJJ. Uptake, translocation, and transformation of quantum dots with cationic versus anionic coatings by Populus deltoides × nigra cuttings. Environ Sci Technol 2014;48:6754–62.

Zhang D, Hua T, Xiao F, Chen C, Gersberg RM, Liu Y, et al. Uptake and accumulation of CuO nanoparticles and CdS/ZnS quantum dot nanoparticles by schoenoplectus tabernaemontani in hydroponic mesocosms. Ecol Eng 2014;70:114–23.

Wang Q, Chen J, Zhang H, Lu M, Qiu D, Wen Y, et al. Synthesis of water-soluble quantum dots for monitoring carrier-DNA nanoparticles in plant cells. J Nanosci Nanotechnol 2011;11:2208–14.

Dong X, Liang W, Meziani MJ, Sun YP, Yang L. Carbon dots as potent antimicrobial agents. Theranostics 2020;10:671–86.

Lu Z, Li CM, Bao H, Qiao Y, Toh Y, Yang X. Mechanism of antimicrobial activity of CdTe quantum dots. Langmuir 2008;24:5445–52.

Ristic BZ, Milenkovic MM, Dakic IR, Todorovic Markovic BM, Milosavljevic MS, Budimir MD, et al. Photodynamic antibacterial effect of graphene quantum dots. Biomaterials 2014;35:4428–35.

Kim S, Lim YT, Soltesz EG, De Grand AM, Lee J, Nakayama A, et al. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nat Biotechnol 2004;22:93–7.

Frangioni JV, Kim SW, Ohnishi S, Kim S, Bawendi MG. Sentinel lymph node mapping with type-II quantum dots. Methods Mol Biol 2007;374:147–59.

Pons T, Pic E, Lequeux N, Cassette E, Bezdetnaya L, Guillemin F, et al. Cadmium-free CuInS2/ZnS quantum dots for sentinel lymph node imaging with reduced toxicity. ACS Nano 2010;4:2531–8.

Smith AM, Dave S, Nie S, True L, Gao X. Multicolor quantum dots for molecular diagnostics of cancer. Expert Rev Mol Diagnostics 2006;6:231–44.

Shao L, Gao Y, Yan F. Semiconductor quantum dots for biomedical applications. Sensors 2011;11:11736–51.

Luo G, Long J, Zhang B, Liu C, Ji S, Xu J, et al. Quantum dots in cancer therapy. Expert Opinion Drug Delivery 2012;9:47–58.

Nie S, Xing Y, Kim GJ, Simons JW. Nanotechnology applications in cancer. Annual Rev Biomed Eng 2007;9:257–88.

Wagner MK, Li F, Li J, Li XF, Le XC. Use of quantum dots in the development of assays for cancer biomarkers. Anal Bioanal Chem 2010;397:3213–24.

Nida DL, Rahman MS, Carlson KD, Richards Kortum R, Follen M. Fluorescent nanocrystals for use in early cervical cancer detection. Gynecol Oncol 2005;99(3 Suppl 1):S89-94.

Iga AM, Robertson JHP, Winslet MC, Seifalian AM. Clinical potential of quantum dots. J Biomed Biotechnol 2007;2007:76087.

Kloepfer JA, Mielke RE, Wong MS, Nealson KH, Stucky G, Nadeau JL. Quantum dots as strain-and metabolism-specific microbiological labels. Appl Environ Microbiol 2003;69:4205–13.

Liang J, Huang S, Zeng D, He Z, Ji X, Ai X, et al. CdSe quantum dots as luminescent probes for spironolactone determination. Talanta 2006;69:126–30.