The enzyme-sensitive release of prodigiosin grafted β-cyclodextrin and chitosan magnetic nanoparticles as an anticancer drug delivery system: Synthesis, characterization and cytotoxicity studies
[Display omitted] •Polysaccharide coated nanocarriers were synthesized to design a drug release strategy.•Prodigiosin was chosen to survey its encapsulation on the synthesized nanocarriers.•Glycoside hydrolases were used to analysis the in vitro release of the drug.•PG-loaded nanocarriers showed sui...
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Veröffentlicht in: | Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2017-10, Vol.158, p.589-601 |
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creator | Rastegari, Banafsheh Karbalaei-Heidari, Hamid Reza Zeinali, Sedigheh Sheardown, Heather |
description | [Display omitted]
•Polysaccharide coated nanocarriers were synthesized to design a drug release strategy.•Prodigiosin was chosen to survey its encapsulation on the synthesized nanocarriers.•Glycoside hydrolases were used to analysis the in vitro release of the drug.•PG-loaded nanocarriers showed suitable cytotoxicity on cancerous cell lines.•Microscopy analysis confirmed specific targeting of nanocarriers to cancerous cells.
In present investigation, two glucose based smart tumor-targeted drug delivery systems coupled with enzyme-sensitive release strategy are introduced. Magnetic nanoparticles (Fe3O4) were grafted with carboxymethyl chitosan (CS) and β-cyclodextrin (β-CD) as carriers. Prodigiosin (PG) was used as the model anti-tumor drug, targeting aggressive tumor cells. The morphology, properties and composition and grafting process were characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), vibration sample magnetometer (VSM), X-ray diffraction (XRD) analysis. The results revealed that the core crystal size of the nanoparticles synthesized were 14.2±2.1 and 9.8±1.4nm for β-CD and CS-MNPs respectively when measured using TEM; while dynamic light scattering (DLS) gave diameters of 121.1 and 38.2nm. The saturation magnetization (Ms) of bare magnetic nanoparticles is 50.10emucm−3, while modification with β-CD and CS gave values of 37.48 and 65.01emucm−3, respectively. The anticancer compound, prodigiosin (PG) was loaded into the NPs with an encapsulation efficiency of approximately 81% for the β-CD-MNPs, and 92% for the CS-MNPs. This translates to a drug loading capacity of 56.17 and 59.17mg/100mg MNPs, respectively. Measurement of in vitro release of prodigiosin from the loaded nanocarriers in the presence of the hydrolytic enzymes, alpha-amylase and chitosanase showed that 58.1 and 44.6% of the drug was released after one-hour of incubation. Cytotoxicity studies of PG-loaded nanocarriers on two cancer cell lines, MCF-7 and HepG2, and on a non-cancerous control, NIH/3T3 cells, revealed that the drug loaded nanoparticles had greater efficacy on the cancer cell lines. The selective index (SI) for free PG on MCF-7 and HepG2 cells was 1.54 and 4.42 respectively. This parameter was reduced for PG-loaded β-CD-MNPs to 1.27 and 1.85, while the SI for CS-MNPs improved considerably to 7.03 on MCF-7 cells. Complementary studies by fluorescence and confocal microscopy and flow cytometry confirm specific targeting of |
doi_str_mv | 10.1016/j.colsurfb.2017.07.044 |
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•Polysaccharide coated nanocarriers were synthesized to design a drug release strategy.•Prodigiosin was chosen to survey its encapsulation on the synthesized nanocarriers.•Glycoside hydrolases were used to analysis the in vitro release of the drug.•PG-loaded nanocarriers showed suitable cytotoxicity on cancerous cell lines.•Microscopy analysis confirmed specific targeting of nanocarriers to cancerous cells.
In present investigation, two glucose based smart tumor-targeted drug delivery systems coupled with enzyme-sensitive release strategy are introduced. Magnetic nanoparticles (Fe3O4) were grafted with carboxymethyl chitosan (CS) and β-cyclodextrin (β-CD) as carriers. Prodigiosin (PG) was used as the model anti-tumor drug, targeting aggressive tumor cells. The morphology, properties and composition and grafting process were characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), vibration sample magnetometer (VSM), X-ray diffraction (XRD) analysis. The results revealed that the core crystal size of the nanoparticles synthesized were 14.2±2.1 and 9.8±1.4nm for β-CD and CS-MNPs respectively when measured using TEM; while dynamic light scattering (DLS) gave diameters of 121.1 and 38.2nm. The saturation magnetization (Ms) of bare magnetic nanoparticles is 50.10emucm−3, while modification with β-CD and CS gave values of 37.48 and 65.01emucm−3, respectively. The anticancer compound, prodigiosin (PG) was loaded into the NPs with an encapsulation efficiency of approximately 81% for the β-CD-MNPs, and 92% for the CS-MNPs. This translates to a drug loading capacity of 56.17 and 59.17mg/100mg MNPs, respectively. Measurement of in vitro release of prodigiosin from the loaded nanocarriers in the presence of the hydrolytic enzymes, alpha-amylase and chitosanase showed that 58.1 and 44.6% of the drug was released after one-hour of incubation. Cytotoxicity studies of PG-loaded nanocarriers on two cancer cell lines, MCF-7 and HepG2, and on a non-cancerous control, NIH/3T3 cells, revealed that the drug loaded nanoparticles had greater efficacy on the cancer cell lines. The selective index (SI) for free PG on MCF-7 and HepG2 cells was 1.54 and 4.42 respectively. This parameter was reduced for PG-loaded β-CD-MNPs to 1.27 and 1.85, while the SI for CS-MNPs improved considerably to 7.03 on MCF-7 cells. Complementary studies by fluorescence and confocal microscopy and flow cytometry confirm specific targeting of the nanocarriers to the cancer cells. The results suggest that CS-MNPs have higher potency and are better able to target the prodigiosin toxicity effect on cancerous cells than β-CD-MNPs.</description><identifier>ISSN: 0927-7765</identifier><identifier>EISSN: 1873-4367</identifier><identifier>DOI: 10.1016/j.colsurfb.2017.07.044</identifier><identifier>PMID: 28750341</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Antineoplastic Agents - chemistry ; beta-Cyclodextrins - chemistry ; Chitosan - chemistry ; Drug Delivery Systems - methods ; Lysosomal enzymes ; Lysosomes - chemistry ; Magnetite Nanoparticles - chemistry ; Microscopy, Electron, Transmission ; Polysaccharide coating ; Prodigiosin ; Prodigiosin - chemistry ; Selective delivery ; Spectroscopy, Fourier Transform Infrared ; X-Ray Diffraction</subject><ispartof>Colloids and surfaces, B, Biointerfaces, 2017-10, Vol.158, p.589-601</ispartof><rights>2017 Elsevier B.V.</rights><rights>Copyright © 2017 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c416t-def9779f455c7233a2587eb835a638ab1563eff8223d2cfbdbd773b39bd62afa3</citedby><cites>FETCH-LOGICAL-c416t-def9779f455c7233a2587eb835a638ab1563eff8223d2cfbdbd773b39bd62afa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0927776517304563$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28750341$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rastegari, Banafsheh</creatorcontrib><creatorcontrib>Karbalaei-Heidari, Hamid Reza</creatorcontrib><creatorcontrib>Zeinali, Sedigheh</creatorcontrib><creatorcontrib>Sheardown, Heather</creatorcontrib><title>The enzyme-sensitive release of prodigiosin grafted β-cyclodextrin and chitosan magnetic nanoparticles as an anticancer drug delivery system: Synthesis, characterization and cytotoxicity studies</title><title>Colloids and surfaces, B, Biointerfaces</title><addtitle>Colloids Surf B Biointerfaces</addtitle><description>[Display omitted]
•Polysaccharide coated nanocarriers were synthesized to design a drug release strategy.•Prodigiosin was chosen to survey its encapsulation on the synthesized nanocarriers.•Glycoside hydrolases were used to analysis the in vitro release of the drug.•PG-loaded nanocarriers showed suitable cytotoxicity on cancerous cell lines.•Microscopy analysis confirmed specific targeting of nanocarriers to cancerous cells.
In present investigation, two glucose based smart tumor-targeted drug delivery systems coupled with enzyme-sensitive release strategy are introduced. Magnetic nanoparticles (Fe3O4) were grafted with carboxymethyl chitosan (CS) and β-cyclodextrin (β-CD) as carriers. Prodigiosin (PG) was used as the model anti-tumor drug, targeting aggressive tumor cells. The morphology, properties and composition and grafting process were characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), vibration sample magnetometer (VSM), X-ray diffraction (XRD) analysis. The results revealed that the core crystal size of the nanoparticles synthesized were 14.2±2.1 and 9.8±1.4nm for β-CD and CS-MNPs respectively when measured using TEM; while dynamic light scattering (DLS) gave diameters of 121.1 and 38.2nm. The saturation magnetization (Ms) of bare magnetic nanoparticles is 50.10emucm−3, while modification with β-CD and CS gave values of 37.48 and 65.01emucm−3, respectively. The anticancer compound, prodigiosin (PG) was loaded into the NPs with an encapsulation efficiency of approximately 81% for the β-CD-MNPs, and 92% for the CS-MNPs. This translates to a drug loading capacity of 56.17 and 59.17mg/100mg MNPs, respectively. Measurement of in vitro release of prodigiosin from the loaded nanocarriers in the presence of the hydrolytic enzymes, alpha-amylase and chitosanase showed that 58.1 and 44.6% of the drug was released after one-hour of incubation. Cytotoxicity studies of PG-loaded nanocarriers on two cancer cell lines, MCF-7 and HepG2, and on a non-cancerous control, NIH/3T3 cells, revealed that the drug loaded nanoparticles had greater efficacy on the cancer cell lines. The selective index (SI) for free PG on MCF-7 and HepG2 cells was 1.54 and 4.42 respectively. This parameter was reduced for PG-loaded β-CD-MNPs to 1.27 and 1.85, while the SI for CS-MNPs improved considerably to 7.03 on MCF-7 cells. Complementary studies by fluorescence and confocal microscopy and flow cytometry confirm specific targeting of the nanocarriers to the cancer cells. The results suggest that CS-MNPs have higher potency and are better able to target the prodigiosin toxicity effect on cancerous cells than β-CD-MNPs.</description><subject>Antineoplastic Agents - chemistry</subject><subject>beta-Cyclodextrins - chemistry</subject><subject>Chitosan - chemistry</subject><subject>Drug Delivery Systems - methods</subject><subject>Lysosomal enzymes</subject><subject>Lysosomes - chemistry</subject><subject>Magnetite Nanoparticles - chemistry</subject><subject>Microscopy, Electron, Transmission</subject><subject>Polysaccharide coating</subject><subject>Prodigiosin</subject><subject>Prodigiosin - chemistry</subject><subject>Selective delivery</subject><subject>Spectroscopy, Fourier Transform Infrared</subject><subject>X-Ray Diffraction</subject><issn>0927-7765</issn><issn>1873-4367</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUcuOEzEQHCEQGxZ-YeUjByb4NfaEE2jFS1qJA8vZ8tjtxNGMHWzPamc_i1_gzjfhKFmuSCV1t1XVJXc1zRXBa4KJeLtfmzjmOblhTTGRa1zB-ZNmRXrJWs6EfNqs8IbKVkrRXTQvct5jjCkn8nlzQXvZYcbJqvl9uwME4WGZoM0Qsi_-DlCCEXQGFB06pGj91sfsA9om7QpY9OdXaxYzRgv3JdV3HSwyO19i1gFNehugeIOCDvGgU21HyEhXHJl11MFAQjbNW2RhrH5pQXnJBaZ36PsSyg6yz2_qRp20KZD8gy4-nm2WEku898aXKiqz9ZBfNs-cHjO8OtfL5senj7fXX9qbb5-_Xn-4aQ0norQW3EbKjeNdZyRlTNOulzD0rNOC9XognWDgXE8ps9S4wQ5WSjawzWAF1U6zy-b1aW-9yc8ZclGTzwbGUQeIc1ZkQ7nAXNC-UsWJalLMOYFTh-QnnRZFsDoGqPbqMUB1DFDhCs6r8OrsMQ8T2H-yx8Qq4f2JAPWndx6SysZDvaj1CUxRNvr_efwFAS24cw</recordid><startdate>20171001</startdate><enddate>20171001</enddate><creator>Rastegari, Banafsheh</creator><creator>Karbalaei-Heidari, Hamid Reza</creator><creator>Zeinali, Sedigheh</creator><creator>Sheardown, Heather</creator><general>Elsevier B.V</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>7X8</scope></search><sort><creationdate>20171001</creationdate><title>The enzyme-sensitive release of prodigiosin grafted β-cyclodextrin and chitosan magnetic nanoparticles as an anticancer drug delivery system: Synthesis, characterization and cytotoxicity studies</title><author>Rastegari, Banafsheh ; Karbalaei-Heidari, Hamid Reza ; Zeinali, Sedigheh ; Sheardown, Heather</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-def9779f455c7233a2587eb835a638ab1563eff8223d2cfbdbd773b39bd62afa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Antineoplastic Agents - chemistry</topic><topic>beta-Cyclodextrins - chemistry</topic><topic>Chitosan - chemistry</topic><topic>Drug Delivery Systems - methods</topic><topic>Lysosomal enzymes</topic><topic>Lysosomes - chemistry</topic><topic>Magnetite Nanoparticles - chemistry</topic><topic>Microscopy, Electron, Transmission</topic><topic>Polysaccharide coating</topic><topic>Prodigiosin</topic><topic>Prodigiosin - chemistry</topic><topic>Selective delivery</topic><topic>Spectroscopy, Fourier Transform Infrared</topic><topic>X-Ray Diffraction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rastegari, Banafsheh</creatorcontrib><creatorcontrib>Karbalaei-Heidari, Hamid Reza</creatorcontrib><creatorcontrib>Zeinali, Sedigheh</creatorcontrib><creatorcontrib>Sheardown, Heather</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Colloids and surfaces, B, Biointerfaces</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rastegari, Banafsheh</au><au>Karbalaei-Heidari, Hamid Reza</au><au>Zeinali, Sedigheh</au><au>Sheardown, Heather</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The enzyme-sensitive release of prodigiosin grafted β-cyclodextrin and chitosan magnetic nanoparticles as an anticancer drug delivery system: Synthesis, characterization and cytotoxicity studies</atitle><jtitle>Colloids and surfaces, B, Biointerfaces</jtitle><addtitle>Colloids Surf B Biointerfaces</addtitle><date>2017-10-01</date><risdate>2017</risdate><volume>158</volume><spage>589</spage><epage>601</epage><pages>589-601</pages><issn>0927-7765</issn><eissn>1873-4367</eissn><abstract>[Display omitted]
•Polysaccharide coated nanocarriers were synthesized to design a drug release strategy.•Prodigiosin was chosen to survey its encapsulation on the synthesized nanocarriers.•Glycoside hydrolases were used to analysis the in vitro release of the drug.•PG-loaded nanocarriers showed suitable cytotoxicity on cancerous cell lines.•Microscopy analysis confirmed specific targeting of nanocarriers to cancerous cells.
In present investigation, two glucose based smart tumor-targeted drug delivery systems coupled with enzyme-sensitive release strategy are introduced. Magnetic nanoparticles (Fe3O4) were grafted with carboxymethyl chitosan (CS) and β-cyclodextrin (β-CD) as carriers. Prodigiosin (PG) was used as the model anti-tumor drug, targeting aggressive tumor cells. The morphology, properties and composition and grafting process were characterized by transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), vibration sample magnetometer (VSM), X-ray diffraction (XRD) analysis. The results revealed that the core crystal size of the nanoparticles synthesized were 14.2±2.1 and 9.8±1.4nm for β-CD and CS-MNPs respectively when measured using TEM; while dynamic light scattering (DLS) gave diameters of 121.1 and 38.2nm. The saturation magnetization (Ms) of bare magnetic nanoparticles is 50.10emucm−3, while modification with β-CD and CS gave values of 37.48 and 65.01emucm−3, respectively. The anticancer compound, prodigiosin (PG) was loaded into the NPs with an encapsulation efficiency of approximately 81% for the β-CD-MNPs, and 92% for the CS-MNPs. This translates to a drug loading capacity of 56.17 and 59.17mg/100mg MNPs, respectively. Measurement of in vitro release of prodigiosin from the loaded nanocarriers in the presence of the hydrolytic enzymes, alpha-amylase and chitosanase showed that 58.1 and 44.6% of the drug was released after one-hour of incubation. Cytotoxicity studies of PG-loaded nanocarriers on two cancer cell lines, MCF-7 and HepG2, and on a non-cancerous control, NIH/3T3 cells, revealed that the drug loaded nanoparticles had greater efficacy on the cancer cell lines. The selective index (SI) for free PG on MCF-7 and HepG2 cells was 1.54 and 4.42 respectively. This parameter was reduced for PG-loaded β-CD-MNPs to 1.27 and 1.85, while the SI for CS-MNPs improved considerably to 7.03 on MCF-7 cells. Complementary studies by fluorescence and confocal microscopy and flow cytometry confirm specific targeting of the nanocarriers to the cancer cells. The results suggest that CS-MNPs have higher potency and are better able to target the prodigiosin toxicity effect on cancerous cells than β-CD-MNPs.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>28750341</pmid><doi>10.1016/j.colsurfb.2017.07.044</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Antineoplastic Agents - chemistry beta-Cyclodextrins - chemistry Chitosan - chemistry Drug Delivery Systems - methods Lysosomal enzymes Lysosomes - chemistry Magnetite Nanoparticles - chemistry Microscopy, Electron, Transmission Polysaccharide coating Prodigiosin Prodigiosin - chemistry Selective delivery Spectroscopy, Fourier Transform Infrared X-Ray Diffraction |
title | The enzyme-sensitive release of prodigiosin grafted β-cyclodextrin and chitosan magnetic nanoparticles as an anticancer drug delivery system: Synthesis, characterization and cytotoxicity studies |
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