{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:40:40Z","timestamp":1790883640005,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T00:00:00Z","timestamp":1675123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Science and Higher Education of the Russian Federation","award":["\u21162021-0005"],"award-info":[{"award-number":["\u21162021-0005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Quantum dots (QDs) have attracted great attention as tools for theranostics that combine the possibility of simultaneous biological target visualization and medicine delivery. Here, we address whether core\/shell InP\/ZnS QDs (InP-QDs) may be an alternative to toxic Cd-based QDs. We analyze InP-QD photophysical characteristics in cell culture medium, salt solutions, and directly in the cells. It was demonstrated that InP-QDs were internalized into endolysosomes in HeLa and A549 cells with dynamics similar to Cd-based QDs of the same design, but the two cell lines accumulated them with different efficiencies. InP-QDs were reliably detected in the endosomes despite their low quantum yields. Cell culture medium efficiently decreased the InP-QD photoluminescence lifetime by 50%, acidic pH (4.0) had a moderate effect (20\u201325% reduction), and quenching by salt solutions typical of intra-endosomal medium composition resulted in a decrease of about 10\u201315%. The single-vesicle fluorescence-lifetime imaging microscopy analysis of QDs inside and outside the cells shows that the scatter between endosomes in the same cell can be significant, which indicates the complex impact of the abovementioned factors on the state of InP-QDs. The PI test and MTT test demonstrate that InP-QDs are toxic for both cell lines at concentrations higher than 20 nM. Possible reasons for InP-QD toxicity are discussed.<\/jats:p>","DOI":"10.3390\/ijms24032699","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T02:29:03Z","timestamp":1675218543000},"page":"2699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Microenvironmental Impact on InP\/ZnS-Based Quantum Dots in In Vitro Models and in Living Cells: Spectrally- and Time-Resolved Luminescence Analysis"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2012-7338","authenticated-orcid":false,"given":"Ilia","family":"Litvinov","sequence":"first","affiliation":[{"name":"Institute of Cytology, Russian Academy of Sciences,194064 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Salova","sequence":"additional","affiliation":[{"name":"Institute of Cytology, Russian Academy of Sciences,194064 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay","family":"Aksenov","sequence":"additional","affiliation":[{"name":"Institute of Cytology, Russian Academy of Sciences,194064 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Kornilova","sequence":"additional","affiliation":[{"name":"Institute of Cytology, Russian Academy of Sciences,194064 Saint Petersburg, Russia"},{"name":"Higher School of Biomedical Systems and Technologies, Peter the Great St. Petersburg Polytechnic University, 195251 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8547-2880","authenticated-orcid":false,"given":"Tatiana","family":"Belyaeva","sequence":"additional","affiliation":[{"name":"Institute of Cytology, Russian Academy of Sciences,194064 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.chembiol.2010.11.013","article-title":"Biocompatible quantum dots for biological applications","volume":"18","author":"Rosenthal","year":"2011","journal-title":"Chem. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.bios.2012.09.025","article-title":"Applications of quantum dots as probes in immunosensing of small-sized analytes","volume":"41","year":"2013","journal-title":"Biosens. Bioelectron."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1021\/acsmacrolett.9b00891","article-title":"Semiconductor Quantum Dots Are Efficient and Recyclable Photocatalysts for Aqueous PET-RAFT Polymerization","volume":"9","author":"McClelland","year":"2019","journal-title":"ACS Macro Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1039\/C9PY01604J","article-title":"PET-RAFT polymerization catalyzed by cadmium selenide quantum dots (QDs): Grafting-from QDs photocatalysts to make polymer nanocomposites","volume":"11","author":"Zhu","year":"2020","journal-title":"Polym. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"204903","DOI":"10.1063\/5.0051893","article-title":"Enhancing the efficiency of semiconducting quantum dot photocatalyzed atom transfer radical polymerization by ligand shell engineering","volume":"154","author":"Zhu","year":"2021","journal-title":"J. Chem. Phys."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/sj.bjp.0705111","article-title":"Apoptosis and necrosis: Two distinct events induced by cadmium in cortical neurons in culture","volume":"138","author":"Figueroa","year":"2003","journal-title":"Br. J. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1007\/s00253-017-8140-9","article-title":"Cadmium-containing quantum dots: Properties, applications, and toxicity","volume":"101","author":"Mo","year":"2017","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1021\/nl047996m","article-title":"Cytotoxicity of colloidal CdSe and CdSe\/ZnS nanoparticles","volume":"5","author":"Kirchner","year":"2005","journal-title":"Nano Lett."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.addr.2008.03.015","article-title":"Bioconjugated quantum dots for in vivo molecular and cellular imaging","volume":"60","author":"Smith","year":"2008","journal-title":"Adv. Drug Deliver. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1477-3155-8-7","article-title":"Long-term exposure of CdTe quantum dots on PC12 cellular activity and the determination of optimum non-toxic concentrations for biological use","volume":"8","author":"Prasad","year":"2010","journal-title":"J. Nanobiotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1039\/c1nr10131e","article-title":"Cytotoxicity of InP\/ZnS quantum dots related to reactive oxygen species generation","volume":"3","author":"Chibli","year":"2011","journal-title":"Nanoscale"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.pnsc.2019.11.007","article-title":"Recent advances in non-toxic quantum dots and their biomedical applications","volume":"29","author":"Zhu","year":"2019","journal-title":"Prog. Nat. Sci. Mater. Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"681","DOI":"10.7150\/thno.3692","article-title":"Preparation of quantum dot\/drug nanoparticles formulations for traceable targeted delivery and therapy","volume":"2","author":"Young","year":"2012","journal-title":"Theranostics"},{"key":"ref_14","unstructured":"Brki\u0107, S. (2018). Ionizing Radiation Effects and Applications, IntechOpen."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Granada-Ram\u00edrez, D., Arias-Cer\u00f3n, J.S., Rodr\u00edguez-Fragoso, P., Vazquez, F., Luna-Arias, J.P., Herrera-Perez, J.L., and Mendoza-Alvarez, J. (2018). Nanobiomaterials Nanostructured Materials for Biomedical Applications, Elsevier.","DOI":"10.1016\/B978-0-08-100716-7.00016-7"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/j.1471-4159.2010.06626.x","article-title":"TRP channels of intracellular membranes","volume":"113","author":"Dong","year":"2010","journal-title":"J. Neurochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6029","DOI":"10.18632\/oncotarget.6720","article-title":"Quantum dots implementation as a label for analysis of early stages of EGF receptor endocytosis: A comparative study on cultured cells","volume":"7","author":"Salova","year":"2016","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"44335","DOI":"10.18632\/oncotarget.17873","article-title":"EGF receptor lysosomal degradation is delayed in the cells stimulated with EGF-Quantum dot bioconjugate but earlier key events of endocytic degradative pathway are similar to that of native EGF","volume":"8","author":"Salova","year":"2017","journal-title":"Oncotarget"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.1021\/cm034081k","article-title":"Experimental Determination of the Extinction Coefficient of CdTe, CdSe, and CdS","volume":"15","author":"Yu","year":"2003","journal-title":"Nanocryst. Chem. Mater."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"21922","DOI":"10.1039\/C5TA04925C","article-title":"InP and Sn:InP based quantum dot sensitized solar cells","volume":"3","author":"Yang","year":"2015","journal-title":"J. Mater. Chem. A"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/bio.3438","article-title":"Comprehensive study of interaction between biocompatible PEG-InP\/ZnS QDs and bovine serum albumin","volume":"33","author":"Sannaikar","year":"2017","journal-title":"Luminescence"},{"key":"ref_22","first-page":"964","article-title":"Highly Photoluminescent InP Based Core Alloy Shell QDs from Air-Stable Precursors: Excitation Wavelength Dependent Photoluminescence Quantum Yield, Photoluminescence Decay Dynamics, and Single Particle Blinking Dynamics","volume":"122","author":"De","year":"2018","journal-title":"J. Phys. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6569","DOI":"10.1021\/acsaem.8b01453","article-title":"Highly Photoconductive InP Quantum Dots Films and Solar Cells (2018)","volume":"1","author":"Crisp","year":"2018","journal-title":"ACS Appl. Energy Mater."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Damalakiene, L., Karabanovas, V., Bagdonas, S., and Rotomskis, R. (2016). Fluorescence-Lifetime Imaging Microscopy for Visualization of Quantum Dots\u2019 Endocytic Pathway. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17040473"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Matiushkina, A., Litvinov, I., Bazhenova, A., Belyaeva, T., Dubavik, A., Veniaminov, A., Maslov, V., Kornilova, E., and Orlova, A. (2022). Time- and Spectrally-Resolved Photoluminescence Study of Alloyed CdxZn1-xSeyS1-y\/ZnS Quantum Dots and Their Nanocomposites with SPIONs in Living Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23074061"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1134\/S1990519X18020050","article-title":"Quantum Dots based on Indium Phosphide (InP): The Effect of Chemical Modifications of the Organic Shell on Interaction with Cultured Cells of Various Origins","volume":"12","author":"Litvinov","year":"2018","journal-title":"Cell Tissue Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1021\/bc100372u","article-title":"Bidirectional Fluorescence Resonance Energy Transfer (FRET) in Mutated and Chemically Modified Yellow Fluorescent Protein (YFP)","volume":"22","author":"Abraham","year":"2011","journal-title":"Bioconjug. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1907633","DOI":"10.1002\/smll.201907633","article-title":"In Situ Investigation on the Protein Corona Formation of Quantum Dots by Using Fluorescence Resonance Energy Transfer","volume":"16","author":"Qu","year":"2020","journal-title":"Small"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1146\/annurev-physiol-012110-142317","article-title":"Lysosomal acidification mechanisms","volume":"74","author":"Mindell","year":"2012","journal-title":"Annu. Rev. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"183341","DOI":"10.1016\/j.bbamem.2020.183341","article-title":"Regulation and function of V-ATPases in physiology and disease","volume":"1862","author":"Collins","year":"2020","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1093\/toxsci\/kfp087","article-title":"Mechanisms of quantum dot nanoparticle cellular uptake","volume":"110","author":"Zhang","year":"2009","journal-title":"Toxicol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1166\/jbn.2014.1770","article-title":"Surface Properties of Quantum Dots Define Their Cellular Endocytic Routes, Mitogenic Stimulation and Suppression of Cell Migration","volume":"10","author":"Karabanovas","year":"2014","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kamentseva, R., Kosheverova, V., Kharchenko, M., Zlobina, M., Salova, A., Belyaeva, T., Nikolsky, N., and Kornilova, E. (2020). Functional cycle of EEA1-positive early endosome: Direct evidence for pre-existing compartment of degradative pathway. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0232532"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1093\/toxsci\/kfn137","article-title":"Induction of autophagy in porcine kidney cells by quantum dots: A common cellular response to nanomaterials?","volume":"106","author":"Stern","year":"2008","journal-title":"Toxicol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1039\/C2NR33024E","article-title":"InP\/ZnS as a safer alternative to CdSe\/ZnS core\/shell quantum dots: In vitro and in vivo toxicity assessment","volume":"5","author":"Brunetti","year":"2013","journal-title":"Nanoscale"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1039\/c3mt20234h","article-title":"Comparison of cytotoxicity and expression of metal regulatory genes in zebrafish (Danio rerio) liver cells exposed to cadmium sulfate, zinc sulfate and quantum dots","volume":"5","author":"Tang","year":"2013","journal-title":"Metallomics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1021\/tx5000975","article-title":"Cytotoxicity of cadmium-free quantum dots and their use in cell bioimaging","volume":"27","author":"Soenen","year":"2014","journal-title":"Chem. Res. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.msec.2015.07.044","article-title":"Cytotoxicity assessment of functionalized CdSe, CdTe and InP quantum dots in two human cancer cell models","volume":"57","author":"Liu","year":"2015","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.nano.2014.10.002","article-title":"In vivo toxicity assessment of non-cadmium quantum dots in BALB\/c mice","volume":"11","author":"Lin","year":"2015","journal-title":"Nanomed. Nanotechnol."},{"key":"ref_40","first-page":"20","article-title":"Surface Density of Charged Functional Groups on Quantum Dots Determines Their Intracellular Compartmentalization and Biocompatibility","volume":"1","author":"Williams","year":"2017","journal-title":"Asp. Nanotechnol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1117\/1.1506706","article-title":"Quantum-dot nanocrystals for ultrasensitive biological labeling and multicolor optical encoding","volume":"7","author":"Gao","year":"2002","journal-title":"J. Biomed. Opt."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9062","DOI":"10.1021\/nn203272p","article-title":"Probing the \u201cdark\u201d fraction of core-shell quantum dots by ensemble and single particle pH-dependent spectroscopy","volume":"5","author":"Durisic","year":"2011","journal-title":"ACS Nano"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.1021\/ja047000+","article-title":"Size-Dependent Dissociation pH of Thiolate Ligands from Cadmium Chalcogenide Nanocrystals","volume":"127","author":"Aldana","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s11237-005-0025-9","article-title":"Quantum size effects in photonics of semiconductor nanoparticles","volume":"41","author":"Stroyuk","year":"2005","journal-title":"Theor. Exp. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1021\/jp0654718","article-title":"pH-Sensitive Photoluminescence of CdSe\/ZnSe\/ZnS Quantum Dots in Human Ovarian Cancer Cells","volume":"111","author":"Liu","year":"2007","journal-title":"J. Phys. Chem. C"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1134\/S1990519X21010065","article-title":"Changes in the Fluorescence Characteristics of Quantum Dots Based on InP\/ZnS during the Interaction with Cells","volume":"15","author":"Litvinov","year":"2021","journal-title":"Cell Tissue Biol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kritchenkov, I.S., Solomatina, A.I., Kozina, D.O., Porsev, V.V., Sokolov, V.V., Shirmanova, M.V., Lukina, M.M., Komarova, A.D., Shcheslavskiy, V.I., and Belyaeva, T.N. (2021). Biocompatible Ir(III) Complexes as Oxygen Sensors for Phosphorescence Lifetime Imaging. Molecules, 26.","DOI":"10.3390\/molecules26102898"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"763","DOI":"10.3389\/fphar.2018.00763","article-title":"Cytotoxicity of InP\/ZnS quantum dots with different surface functional groups toward two lung-derived cell lines","volume":"9","author":"Chen","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Ayupova, D., Dobhal, G., Laufersky, G., Nann, T., and Goreham, R. (2019). An In Vitro Investigation of Cytotoxic Effects of InP\/Zns Quantum Dots with Different Surface Chemistries. Nanomaterials, 9.","DOI":"10.3390\/nano9020135"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"101549","DOI":"10.1016\/j.redox.2020.101549","article-title":"Single cell-based fluorescence lifetime imaging of intracellular oxygenation and metabolism","volume":"34","author":"Penjweini","year":"2020","journal-title":"Redox Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1002\/smll.201503316","article-title":"In Situ Monitoring of the Intracellular Stability of Nanoparticles by Using Fluorescence Lifetime Imaging","volume":"12","author":"Shang","year":"2015","journal-title":"Small"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1002\/smll.200800088","article-title":"CdTe Nanoparticles Display Tropism to Core Histones and Histone-Rich Cell Organelles","volume":"4","author":"Conroy","year":"2008","journal-title":"Small"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"137401","DOI":"10.1103\/PhysRevLett.88.137401","article-title":"Fluorescence Decay Time of Single Semiconductor Nanocrystals","volume":"88","author":"Schlegel","year":"2002","journal-title":"Phys. Rev. Lett."},{"key":"ref_54","unstructured":"Parker, C.A. (1968). Photoluminescence of Solutions: With Applications to Photochemistry and Analytical Chemistry, Elsevier Publishing Co."},{"key":"ref_55","unstructured":"Lakowicz, E., and Joseph, R. (2013). Principles of Fluorescence Spectroscopy, Springer Science + Business Media."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2699\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:19:40Z","timestamp":1760120380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/3\/2699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,31]]},"references-count":55,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["ijms24032699"],"URL":"https:\/\/doi.org\/10.3390\/ijms24032699","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,31]]}}}