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Light-sensitive ruthenium complex-loaded cross-linked polymeric nanoassemblies for the treatment of cancer
This work focuses on improving the efficacy of photoactivatable Ru complexes for photodynamic therapy by employing cross-linked nanoassemblies (CNAs) as a delivery approach. The effects of complex photoactivation, hydrophobicity, and solution ionic strength and pH on complex loading and release from...
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Published in: | Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2016-01, Vol.4 (3), p.394-48 |
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container_end_page | 48 |
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container_start_page | 394 |
container_title | Journal of materials chemistry. B, Materials for biology and medicine |
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creator | Dickerson, Matthew Howerton, Brock Bae, Younsoo Glazer, Edith |
description | This work focuses on improving the efficacy of photoactivatable Ru complexes for photodynamic therapy by employing cross-linked nanoassemblies (CNAs) as a delivery approach. The effects of complex photoactivation, hydrophobicity, and solution ionic strength and pH on complex loading and release from CNAs were analyzed. The cell cytotoxicity of CNA formulations was similar to free Ru complexes despite reduced or eliminated DNA interactions. The release rate and the amount of each Ru complex released (%) varied inversely with complex hydrophobicity, while the effect of solution ionic strength was dependent on complex hydrophobicity. Premature release of two photoactivatable prodrugs prior to irradiation was believed to account for higher activity in cells studies compared to DNA interaction studies; however, for photostable
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generator-loaded CNAs this cannot explain the high cytotoxicity and lack of DNA interactions because release was incomplete after 48 h. The cause remains unclear, but among other possibilities, accelerated release in a cell culture environment may be responsible.
Cross-linked polymeric nanoassemblies are potential carrier systems for cytotoxic ruthenium complexes, and exhibit a combination of electrostatic and hydrophobic interactions with the metal complexes that impact release rates, release percentages, and biological activity. |
doi_str_mv | 10.1039/c5tb01613d |
format | article |
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1
O
2
generator-loaded CNAs this cannot explain the high cytotoxicity and lack of DNA interactions because release was incomplete after 48 h. The cause remains unclear, but among other possibilities, accelerated release in a cell culture environment may be responsible.
Cross-linked polymeric nanoassemblies are potential carrier systems for cytotoxic ruthenium complexes, and exhibit a combination of electrostatic and hydrophobic interactions with the metal complexes that impact release rates, release percentages, and biological activity.</description><identifier>ISSN: 2050-750X</identifier><identifier>ISSN: 2050-7518</identifier><identifier>EISSN: 2050-7518</identifier><identifier>DOI: 10.1039/c5tb01613d</identifier><identifier>PMID: 26855780</identifier><language>eng</language><publisher>England</publisher><subject>Biotechnology ; cell culture ; Chemical compounds ; Crosslinking ; cytotoxicity ; Deoxyribonucleic acid ; DNA ; Hydrophobicity ; ionic strength ; irradiation ; Nanostructure ; neoplasms ; photochemotherapy ; polymers ; Ruthenium ; singlet oxygen ; Strength</subject><ispartof>Journal of materials chemistry. B, Materials for biology and medicine, 2016-01, Vol.4 (3), p.394-48</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-23df982b555446141a6980e183003908080302db0dfd809cb6419dfb0078e85e3</citedby><cites>FETCH-LOGICAL-c499t-23df982b555446141a6980e183003908080302db0dfd809cb6419dfb0078e85e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26855780$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dickerson, Matthew</creatorcontrib><creatorcontrib>Howerton, Brock</creatorcontrib><creatorcontrib>Bae, Younsoo</creatorcontrib><creatorcontrib>Glazer, Edith</creatorcontrib><title>Light-sensitive ruthenium complex-loaded cross-linked polymeric nanoassemblies for the treatment of cancer</title><title>Journal of materials chemistry. B, Materials for biology and medicine</title><addtitle>J Mater Chem B</addtitle><description>This work focuses on improving the efficacy of photoactivatable Ru complexes for photodynamic therapy by employing cross-linked nanoassemblies (CNAs) as a delivery approach. The effects of complex photoactivation, hydrophobicity, and solution ionic strength and pH on complex loading and release from CNAs were analyzed. The cell cytotoxicity of CNA formulations was similar to free Ru complexes despite reduced or eliminated DNA interactions. The release rate and the amount of each Ru complex released (%) varied inversely with complex hydrophobicity, while the effect of solution ionic strength was dependent on complex hydrophobicity. Premature release of two photoactivatable prodrugs prior to irradiation was believed to account for higher activity in cells studies compared to DNA interaction studies; however, for photostable
1
O
2
generator-loaded CNAs this cannot explain the high cytotoxicity and lack of DNA interactions because release was incomplete after 48 h. The cause remains unclear, but among other possibilities, accelerated release in a cell culture environment may be responsible.
Cross-linked polymeric nanoassemblies are potential carrier systems for cytotoxic ruthenium complexes, and exhibit a combination of electrostatic and hydrophobic interactions with the metal complexes that impact release rates, release percentages, and biological activity.</description><subject>Biotechnology</subject><subject>cell culture</subject><subject>Chemical compounds</subject><subject>Crosslinking</subject><subject>cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Hydrophobicity</subject><subject>ionic strength</subject><subject>irradiation</subject><subject>Nanostructure</subject><subject>neoplasms</subject><subject>photochemotherapy</subject><subject>polymers</subject><subject>Ruthenium</subject><subject>singlet oxygen</subject><subject>Strength</subject><issn>2050-750X</issn><issn>2050-7518</issn><issn>2050-7518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNqNkk1vFSEUhifGxja1G_calsZk6gEGBjYmev2oyU26aRN3hGHO9FJnhiswjf33Ym-96qqFBZDz5D0fvFX1gsIpBa7fOpE7oJLy_kl1xEBA3Qqqnu7v8O2wOknpGspSVCrePKsOmVRCtAqOquu1v9rkOuGcfPY3SOKSNzj7ZSIuTNsRf9ZjsD32xMWQUj36-Xt5bMN4O2H0jsx2DjYlnLrRYyJDiKQIkBzR5gnnTMJAnJ0dxufVwWDHhCf353F1-fnTxeqsXp9_-bp6v65do3WuGe8HrVgnhGgaSRtqpVaAVHEo_YIqmwPrO-iHXoF2nWyo7ocOoFWoBPLj6t1Od7t0E_auFBHtaLbRTzbemmC9-T8y-425CjemabluFS0Cr-8FYvixYMpm8snhONoZw5IMYy1VsqSDB9FSdRk0V1I-AmVSCtqyx6CgpKZasoK-2aF33xNx2PdJwfw2iFmJiw93BvlY4Ff_TmaP_rFDAV7ugJjcPvrXYfwXoJLASQ</recordid><startdate>20160101</startdate><enddate>20160101</enddate><creator>Dickerson, Matthew</creator><creator>Howerton, Brock</creator><creator>Bae, Younsoo</creator><creator>Glazer, Edith</creator><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>JG9</scope><scope>L7M</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20160101</creationdate><title>Light-sensitive ruthenium complex-loaded cross-linked polymeric nanoassemblies for the treatment of cancer</title><author>Dickerson, Matthew ; Howerton, Brock ; Bae, Younsoo ; Glazer, Edith</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-23df982b555446141a6980e183003908080302db0dfd809cb6419dfb0078e85e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Biotechnology</topic><topic>cell culture</topic><topic>Chemical compounds</topic><topic>Crosslinking</topic><topic>cytotoxicity</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Hydrophobicity</topic><topic>ionic strength</topic><topic>irradiation</topic><topic>Nanostructure</topic><topic>neoplasms</topic><topic>photochemotherapy</topic><topic>polymers</topic><topic>Ruthenium</topic><topic>singlet oxygen</topic><topic>Strength</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dickerson, Matthew</creatorcontrib><creatorcontrib>Howerton, Brock</creatorcontrib><creatorcontrib>Bae, Younsoo</creatorcontrib><creatorcontrib>Glazer, Edith</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of materials chemistry. B, Materials for biology and medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dickerson, Matthew</au><au>Howerton, Brock</au><au>Bae, Younsoo</au><au>Glazer, Edith</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Light-sensitive ruthenium complex-loaded cross-linked polymeric nanoassemblies for the treatment of cancer</atitle><jtitle>Journal of materials chemistry. B, Materials for biology and medicine</jtitle><addtitle>J Mater Chem B</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>4</volume><issue>3</issue><spage>394</spage><epage>48</epage><pages>394-48</pages><issn>2050-750X</issn><issn>2050-7518</issn><eissn>2050-7518</eissn><abstract>This work focuses on improving the efficacy of photoactivatable Ru complexes for photodynamic therapy by employing cross-linked nanoassemblies (CNAs) as a delivery approach. The effects of complex photoactivation, hydrophobicity, and solution ionic strength and pH on complex loading and release from CNAs were analyzed. The cell cytotoxicity of CNA formulations was similar to free Ru complexes despite reduced or eliminated DNA interactions. The release rate and the amount of each Ru complex released (%) varied inversely with complex hydrophobicity, while the effect of solution ionic strength was dependent on complex hydrophobicity. Premature release of two photoactivatable prodrugs prior to irradiation was believed to account for higher activity in cells studies compared to DNA interaction studies; however, for photostable
1
O
2
generator-loaded CNAs this cannot explain the high cytotoxicity and lack of DNA interactions because release was incomplete after 48 h. The cause remains unclear, but among other possibilities, accelerated release in a cell culture environment may be responsible.
Cross-linked polymeric nanoassemblies are potential carrier systems for cytotoxic ruthenium complexes, and exhibit a combination of electrostatic and hydrophobic interactions with the metal complexes that impact release rates, release percentages, and biological activity.</abstract><cop>England</cop><pmid>26855780</pmid><doi>10.1039/c5tb01613d</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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source | Royal Society of Chemistry Journals |
subjects | Biotechnology cell culture Chemical compounds Crosslinking cytotoxicity Deoxyribonucleic acid DNA Hydrophobicity ionic strength irradiation Nanostructure neoplasms photochemotherapy polymers Ruthenium singlet oxygen Strength |
title | Light-sensitive ruthenium complex-loaded cross-linked polymeric nanoassemblies for the treatment of cancer |
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