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Cytotoxicity Study on Luminescent Nanocrystals Containing Phospholipid Micelles in Primary Cultures of Rat Astrocytes
Luminescent colloidal nanocrystals (NCs) are emerging as a new tool in neuroscience field, representing superior optical probes for cellular imaging and medical diagnosis of neurological disorders with respect to organic fluorophores. However, only a limited number of studies have, so far, explored...
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Published in: | PloS one 2016-04, Vol.11 (4), p.e0153451 |
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creator | Latronico, Tiziana Depalo, Nicoletta Valente, Gianpiero Fanizza, Elisabetta Laquintana, Valentino Denora, Nunzio Fasano, Anna Striccoli, Marinella Colella, Matilde Agostiano, Angela Curri, M Lucia Liuzzi, Grazia Maria |
description | Luminescent colloidal nanocrystals (NCs) are emerging as a new tool in neuroscience field, representing superior optical probes for cellular imaging and medical diagnosis of neurological disorders with respect to organic fluorophores. However, only a limited number of studies have, so far, explored NC applications in primary neurons, glia and related cells. Indeed astrocytes, as resident cells in the central nervous system (CNS), play an important pathogenic role in several neurodegenerative and neuroinflammatory diseases, therefore enhanced imaging tools for their thorough investigation are strongly amenable. Here, a comprehensive and systematic study on the in vitro toxicological effect of core-shell type luminescent CdSe@ZnS NCs incorporated in polyethylene glycol (PEG) terminated phospholipid micelles on primary cultures of rat astrocytes was carried out. Cytotoxicity response of empty micelles based on PEG modified phospholipids was compared to that of their NC containing counterpart, in order to investigate the effect on cell viability of both inorganic NCs and micelles protecting NC surface. Furthermore, since the surface charge and chemistry influence cell interaction and toxicity, effect of two different functional groups terminating PEG-modified phospholipid micelles, namely amine and carboxyl group, respectively, was evaluated against bare micelles, showing that carboxyl group was less toxic. The ability of PEG-lipid micelles to be internalized into the cells was qualitatively and quantitatively assessed by fluorescence microscopy and photoluminescence (PL) assay. The results of the experiments clearly demonstrate that, once incorporated into the micelles, a low, not toxic, concentration of NCs is sufficient to be distinctly detected within cells. The overall study provides essential indications to define the optimal experimental conditions to effectively and profitably use the proposed luminescent colloidal NCs as optical probe for future in vivo experiments. |
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However, only a limited number of studies have, so far, explored NC applications in primary neurons, glia and related cells. Indeed astrocytes, as resident cells in the central nervous system (CNS), play an important pathogenic role in several neurodegenerative and neuroinflammatory diseases, therefore enhanced imaging tools for their thorough investigation are strongly amenable. Here, a comprehensive and systematic study on the in vitro toxicological effect of core-shell type luminescent CdSe@ZnS NCs incorporated in polyethylene glycol (PEG) terminated phospholipid micelles on primary cultures of rat astrocytes was carried out. Cytotoxicity response of empty micelles based on PEG modified phospholipids was compared to that of their NC containing counterpart, in order to investigate the effect on cell viability of both inorganic NCs and micelles protecting NC surface. Furthermore, since the surface charge and chemistry influence cell interaction and toxicity, effect of two different functional groups terminating PEG-modified phospholipid micelles, namely amine and carboxyl group, respectively, was evaluated against bare micelles, showing that carboxyl group was less toxic. The ability of PEG-lipid micelles to be internalized into the cells was qualitatively and quantitatively assessed by fluorescence microscopy and photoluminescence (PL) assay. The results of the experiments clearly demonstrate that, once incorporated into the micelles, a low, not toxic, concentration of NCs is sufficient to be distinctly detected within cells. The overall study provides essential indications to define the optimal experimental conditions to effectively and profitably use the proposed luminescent colloidal NCs as optical probe for future in vivo experiments.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0153451</identifier><identifier>PMID: 27097043</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Apoptosis ; Astrocytes ; Astrocytes - cytology ; Astrocytes - drug effects ; Astrocytes - metabolism ; Biocompatibility ; Biological Transport ; Biology and Life Sciences ; Blood-brain barrier ; Cadmium ; Cadmium Compounds - chemistry ; Carboxyl group ; Cell Survival - drug effects ; Cells, Cultured ; Central nervous system ; Chemical compounds ; Crystals ; Cytotoxicity ; Cytotoxins - chemistry ; Cytotoxins - metabolism ; Cytotoxins - toxicity ; Dose-Response Relationship, Drug ; Drug delivery systems ; Engineering and Technology ; Female ; Fluorescence ; Fluorescence microscopy ; Fluorophores ; Functional groups ; Inflammation ; Luminescent Agents - chemistry ; Luminescent Agents - metabolism ; Luminescent Agents - toxicity ; Medicine and Health Sciences ; Micelles ; Nanocrystals ; Nanomaterials ; Nanoparticles ; Nanoparticles - chemistry ; Nanoparticles - metabolism ; Nanoparticles - toxicity ; Nervous system ; Neurological diseases ; Neurological disorders ; Neuronal-glial interactions ; Neurosciences ; Optical properties ; Phospholipids ; Phospholipids - chemistry ; Photoluminescence ; Photons ; Physiological aspects ; Polyethylene glycol ; Polyethylene Glycols - chemistry ; Properties ; Quantum dots ; Rats ; Rats, Wistar ; Research and analysis methods ; Selenium Compounds - chemistry ; Studies ; Sulfides - chemistry ; Surface charge ; Toxicity ; Toxicology ; Zinc Compounds - chemistry</subject><ispartof>PloS one, 2016-04, Vol.11 (4), p.e0153451</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Latronico et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Latronico et al 2016 Latronico et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-d7f6193324dedd2ae3126fa5db429efbfb69185e7fe6378dbf088e3db6f259563</citedby><cites>FETCH-LOGICAL-c692t-d7f6193324dedd2ae3126fa5db429efbfb69185e7fe6378dbf088e3db6f259563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1782829865/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1782829865?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,25734,27905,27906,36993,36994,44571,53772,53774,74875</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27097043$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Xu, Bing</contributor><creatorcontrib>Latronico, Tiziana</creatorcontrib><creatorcontrib>Depalo, Nicoletta</creatorcontrib><creatorcontrib>Valente, Gianpiero</creatorcontrib><creatorcontrib>Fanizza, Elisabetta</creatorcontrib><creatorcontrib>Laquintana, Valentino</creatorcontrib><creatorcontrib>Denora, Nunzio</creatorcontrib><creatorcontrib>Fasano, Anna</creatorcontrib><creatorcontrib>Striccoli, Marinella</creatorcontrib><creatorcontrib>Colella, Matilde</creatorcontrib><creatorcontrib>Agostiano, Angela</creatorcontrib><creatorcontrib>Curri, M Lucia</creatorcontrib><creatorcontrib>Liuzzi, Grazia Maria</creatorcontrib><title>Cytotoxicity Study on Luminescent Nanocrystals Containing Phospholipid Micelles in Primary Cultures of Rat Astrocytes</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Luminescent colloidal nanocrystals (NCs) are emerging as a new tool in neuroscience field, representing superior optical probes for cellular imaging and medical diagnosis of neurological disorders with respect to organic fluorophores. However, only a limited number of studies have, so far, explored NC applications in primary neurons, glia and related cells. Indeed astrocytes, as resident cells in the central nervous system (CNS), play an important pathogenic role in several neurodegenerative and neuroinflammatory diseases, therefore enhanced imaging tools for their thorough investigation are strongly amenable. Here, a comprehensive and systematic study on the in vitro toxicological effect of core-shell type luminescent CdSe@ZnS NCs incorporated in polyethylene glycol (PEG) terminated phospholipid micelles on primary cultures of rat astrocytes was carried out. Cytotoxicity response of empty micelles based on PEG modified phospholipids was compared to that of their NC containing counterpart, in order to investigate the effect on cell viability of both inorganic NCs and micelles protecting NC surface. 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The overall study provides essential indications to define the optimal experimental conditions to effectively and profitably use the proposed luminescent colloidal NCs as optical probe for future in vivo experiments.</description><subject>Animals</subject><subject>Apoptosis</subject><subject>Astrocytes</subject><subject>Astrocytes - cytology</subject><subject>Astrocytes - drug effects</subject><subject>Astrocytes - metabolism</subject><subject>Biocompatibility</subject><subject>Biological Transport</subject><subject>Biology and Life Sciences</subject><subject>Blood-brain barrier</subject><subject>Cadmium</subject><subject>Cadmium Compounds - chemistry</subject><subject>Carboxyl group</subject><subject>Cell Survival - drug effects</subject><subject>Cells, Cultured</subject><subject>Central nervous system</subject><subject>Chemical compounds</subject><subject>Crystals</subject><subject>Cytotoxicity</subject><subject>Cytotoxins - chemistry</subject><subject>Cytotoxins - metabolism</subject><subject>Cytotoxins - toxicity</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug delivery systems</subject><subject>Engineering and Technology</subject><subject>Female</subject><subject>Fluorescence</subject><subject>Fluorescence microscopy</subject><subject>Fluorophores</subject><subject>Functional groups</subject><subject>Inflammation</subject><subject>Luminescent Agents - chemistry</subject><subject>Luminescent Agents - metabolism</subject><subject>Luminescent Agents - toxicity</subject><subject>Medicine and Health Sciences</subject><subject>Micelles</subject><subject>Nanocrystals</subject><subject>Nanomaterials</subject><subject>Nanoparticles</subject><subject>Nanoparticles - chemistry</subject><subject>Nanoparticles - metabolism</subject><subject>Nanoparticles - toxicity</subject><subject>Nervous system</subject><subject>Neurological diseases</subject><subject>Neurological disorders</subject><subject>Neuronal-glial interactions</subject><subject>Neurosciences</subject><subject>Optical properties</subject><subject>Phospholipids</subject><subject>Phospholipids - chemistry</subject><subject>Photoluminescence</subject><subject>Photons</subject><subject>Physiological aspects</subject><subject>Polyethylene glycol</subject><subject>Polyethylene Glycols - chemistry</subject><subject>Properties</subject><subject>Quantum dots</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Research and analysis methods</subject><subject>Selenium Compounds - chemistry</subject><subject>Studies</subject><subject>Sulfides - chemistry</subject><subject>Surface charge</subject><subject>Toxicity</subject><subject>Toxicology</subject><subject>Zinc Compounds - chemistry</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYqPwDxBYQkJw0ZLYiZPcIFUVH5UKmzbg1nLs49ZVahfbQcu_x1mzqUW7QL6wdfyc1z6vfZLkZZbOMlJmH7a2c4a3s701MEuzguRF9ig5z2qCpxSn5PHR-ix55v02TQtSUfo0OcNlWpdpTs6TbtEHG-yNFjr06Dp0skfWoFW30wa8ABPQd26scL0PvPVoYU3g2mizRpcb6_cb2-q9luibFtC24JE26NLpHXc9WnRt6FyMWYWueEBzH5wVfQD_PHmiohq8GOdJ8vPzpx-Lr9PVxZflYr6aClrjMJWlorEGgnMJUmIOJMNU8UI2Oa5BNaqhdVYVUCqgpKxko9KqAiIbqnBRF5RMktcH3X1rPRsd8ywrK1zhuqJFJJYHQlq-ZfvDzZnlmt0GrFsz7oIWLbAGU5BVnae0lnlKGs5zaJpSqGg-pERErY_jaV2zAzmY53h7Inq6Y_SGre0fllekwhhHgXejgLO_O_CB7bQffOUGbHd7b1JjguM0Sd78gz5c3UiteSxAG2XjuWIQZfM8_hhMazJQsweoOCTstIjfS-kYP0l4f5IQmQA3Yc0779ny-ur_2Ytfp-zbI3YDvA0bb9suaGv8KZgfQOGs9w7UvclZyobuuHODDd3Bxu6Iaa-OH-g-6a4dyF82dQzn</recordid><startdate>20160420</startdate><enddate>20160420</enddate><creator>Latronico, Tiziana</creator><creator>Depalo, Nicoletta</creator><creator>Valente, Gianpiero</creator><creator>Fanizza, Elisabetta</creator><creator>Laquintana, Valentino</creator><creator>Denora, Nunzio</creator><creator>Fasano, Anna</creator><creator>Striccoli, Marinella</creator><creator>Colella, Matilde</creator><creator>Agostiano, Angela</creator><creator>Curri, M Lucia</creator><creator>Liuzzi, Grazia Maria</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160420</creationdate><title>Cytotoxicity Study on Luminescent Nanocrystals Containing Phospholipid Micelles in Primary Cultures of Rat Astrocytes</title><author>Latronico, Tiziana ; Depalo, Nicoletta ; Valente, Gianpiero ; Fanizza, Elisabetta ; Laquintana, Valentino ; Denora, Nunzio ; Fasano, Anna ; Striccoli, Marinella ; Colella, Matilde ; Agostiano, Angela ; Curri, M Lucia ; Liuzzi, Grazia Maria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-d7f6193324dedd2ae3126fa5db429efbfb69185e7fe6378dbf088e3db6f259563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Astrocytes</topic><topic>Astrocytes - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials science collection</collection><collection>ProQuest - Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Latronico, Tiziana</au><au>Depalo, Nicoletta</au><au>Valente, Gianpiero</au><au>Fanizza, Elisabetta</au><au>Laquintana, Valentino</au><au>Denora, Nunzio</au><au>Fasano, Anna</au><au>Striccoli, Marinella</au><au>Colella, Matilde</au><au>Agostiano, Angela</au><au>Curri, M Lucia</au><au>Liuzzi, Grazia Maria</au><au>Xu, Bing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytotoxicity Study on Luminescent Nanocrystals Containing Phospholipid Micelles in Primary Cultures of Rat Astrocytes</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-04-20</date><risdate>2016</risdate><volume>11</volume><issue>4</issue><spage>e0153451</spage><pages>e0153451-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Luminescent colloidal nanocrystals (NCs) are emerging as a new tool in neuroscience field, representing superior optical probes for cellular imaging and medical diagnosis of neurological disorders with respect to organic fluorophores. However, only a limited number of studies have, so far, explored NC applications in primary neurons, glia and related cells. Indeed astrocytes, as resident cells in the central nervous system (CNS), play an important pathogenic role in several neurodegenerative and neuroinflammatory diseases, therefore enhanced imaging tools for their thorough investigation are strongly amenable. Here, a comprehensive and systematic study on the in vitro toxicological effect of core-shell type luminescent CdSe@ZnS NCs incorporated in polyethylene glycol (PEG) terminated phospholipid micelles on primary cultures of rat astrocytes was carried out. Cytotoxicity response of empty micelles based on PEG modified phospholipids was compared to that of their NC containing counterpart, in order to investigate the effect on cell viability of both inorganic NCs and micelles protecting NC surface. Furthermore, since the surface charge and chemistry influence cell interaction and toxicity, effect of two different functional groups terminating PEG-modified phospholipid micelles, namely amine and carboxyl group, respectively, was evaluated against bare micelles, showing that carboxyl group was less toxic. The ability of PEG-lipid micelles to be internalized into the cells was qualitatively and quantitatively assessed by fluorescence microscopy and photoluminescence (PL) assay. The results of the experiments clearly demonstrate that, once incorporated into the micelles, a low, not toxic, concentration of NCs is sufficient to be distinctly detected within cells. The overall study provides essential indications to define the optimal experimental conditions to effectively and profitably use the proposed luminescent colloidal NCs as optical probe for future in vivo experiments.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27097043</pmid><doi>10.1371/journal.pone.0153451</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2016-04, Vol.11 (4), p.e0153451 |
issn | 1932-6203 1932-6203 |
language | eng |
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source | Open Access: PubMed Central; ProQuest - Publicly Available Content Database |
subjects | Animals Apoptosis Astrocytes Astrocytes - cytology Astrocytes - drug effects Astrocytes - metabolism Biocompatibility Biological Transport Biology and Life Sciences Blood-brain barrier Cadmium Cadmium Compounds - chemistry Carboxyl group Cell Survival - drug effects Cells, Cultured Central nervous system Chemical compounds Crystals Cytotoxicity Cytotoxins - chemistry Cytotoxins - metabolism Cytotoxins - toxicity Dose-Response Relationship, Drug Drug delivery systems Engineering and Technology Female Fluorescence Fluorescence microscopy Fluorophores Functional groups Inflammation Luminescent Agents - chemistry Luminescent Agents - metabolism Luminescent Agents - toxicity Medicine and Health Sciences Micelles Nanocrystals Nanomaterials Nanoparticles Nanoparticles - chemistry Nanoparticles - metabolism Nanoparticles - toxicity Nervous system Neurological diseases Neurological disorders Neuronal-glial interactions Neurosciences Optical properties Phospholipids Phospholipids - chemistry Photoluminescence Photons Physiological aspects Polyethylene glycol Polyethylene Glycols - chemistry Properties Quantum dots Rats Rats, Wistar Research and analysis methods Selenium Compounds - chemistry Studies Sulfides - chemistry Surface charge Toxicity Toxicology Zinc Compounds - chemistry |
title | Cytotoxicity Study on Luminescent Nanocrystals Containing Phospholipid Micelles in Primary Cultures of Rat Astrocytes |
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