Tumor targeted self-synergistic nanoplatforms for arsenic-sensitized photodynamic therapy
Development of antitumor agents with high efficiency and low toxicity is one of the most important goals for biomedical research. However, most traditional therapeutic strategies were limited due to their non-specificity and abnormal tumor microenvironments, causing a poor therapeutic efficiency and...
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| Veröffentlicht in: | Acta biomaterialia 2020-11, Vol.117, p.349-360 |
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| creator | Yuan, Ping Fan, Gui-Ling Zhao, Lin-Ping Liu, Ling-Shan Deng, Fu-An Jiang, Xue-Yan Hu, Ai-Hua Yu, Xi-Yong Chen, A-Li Cheng, Hong Li, Shi-Ying |
| description | Development of antitumor agents with high efficiency and low toxicity is one of the most important goals for biomedical research. However, most traditional therapeutic strategies were limited due to their non-specificity and abnormal tumor microenvironments, causing a poor therapeutic efficiency and severe side effects. In this paper, a tumor targeted self-synergistic nanoplatform (designated as PAO@PCN@HA) was developed for chemotherapy sensitized photodynamic therapy (PDT) against hypoxic tumors. The efficient drug loading of phenylarsine oxide (PAO) in porphyrinic metal organic framework of PCN-224 as well as the surface modification of hyaluronic acid (HA) improved the targeted drug delivery and reduced the side effects of PAO at the therapeutic dose. Particularly, PAO as an arsenical-based chemotherapeutic agent could not only induce cell apoptosis by generating reactive oxygen species (ROS), but also regulate tumor microenvironments to improve the PDT effect of PCN-224 by mitigating hypoxia and consuming cellular GSH. Both in vitro and in vivo investigations confirmed an effective self-synergy of PAO@PCN@HA in hypoxic tumor therapy with a low systemic toxicity. This integration of microenvironment adjustment with tumor targeted self-synergistic mechanism might provide a new insight for the development of arsenic-based antitumor strategy for clinical applications.
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| doi_str_mv | 10.1016/j.actbio.2020.09.047 |
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[Display omitted]</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2020.09.047</identifier><identifier>PMID: 33010514</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Anticancer properties ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Antitumor agents ; Apoptosis ; Arsenic ; Arsenic - therapeutic use ; Biocompatibility ; Biomedical materials ; Cell Line, Tumor ; Chemotherapy ; Drug delivery ; Drug Delivery Systems ; Humans ; Hyaluronic acid ; Hypoxia ; In vivo methods and tests ; Metal-organic frameworks ; Microenvironments ; Neoplasms - drug therapy ; Photochemotherapy ; Photodynamic therapy ; Photosensitizing Agents - therapeutic use ; Reactive oxygen species ; Side effects ; Toxicity ; Tumor Microenvironment ; Tumors</subject><ispartof>Acta biomaterialia, 2020-11, Vol.117, p.349-360</ispartof><rights>2020</rights><rights>Copyright © 2020. Published by Elsevier Ltd.</rights><rights>Copyright Elsevier BV Nov 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-6a3877923dec4d13c79f80e6c3b4cf4025df121ede3579aee97c87daf698a2dc3</citedby><cites>FETCH-LOGICAL-c390t-6a3877923dec4d13c79f80e6c3b4cf4025df121ede3579aee97c87daf698a2dc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.actbio.2020.09.047$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33010514$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yuan, Ping</creatorcontrib><creatorcontrib>Fan, Gui-Ling</creatorcontrib><creatorcontrib>Zhao, Lin-Ping</creatorcontrib><creatorcontrib>Liu, Ling-Shan</creatorcontrib><creatorcontrib>Deng, Fu-An</creatorcontrib><creatorcontrib>Jiang, Xue-Yan</creatorcontrib><creatorcontrib>Hu, Ai-Hua</creatorcontrib><creatorcontrib>Yu, Xi-Yong</creatorcontrib><creatorcontrib>Chen, A-Li</creatorcontrib><creatorcontrib>Cheng, Hong</creatorcontrib><creatorcontrib>Li, Shi-Ying</creatorcontrib><title>Tumor targeted self-synergistic nanoplatforms for arsenic-sensitized photodynamic therapy</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>Development of antitumor agents with high efficiency and low toxicity is one of the most important goals for biomedical research. However, most traditional therapeutic strategies were limited due to their non-specificity and abnormal tumor microenvironments, causing a poor therapeutic efficiency and severe side effects. In this paper, a tumor targeted self-synergistic nanoplatform (designated as PAO@PCN@HA) was developed for chemotherapy sensitized photodynamic therapy (PDT) against hypoxic tumors. The efficient drug loading of phenylarsine oxide (PAO) in porphyrinic metal organic framework of PCN-224 as well as the surface modification of hyaluronic acid (HA) improved the targeted drug delivery and reduced the side effects of PAO at the therapeutic dose. Particularly, PAO as an arsenical-based chemotherapeutic agent could not only induce cell apoptosis by generating reactive oxygen species (ROS), but also regulate tumor microenvironments to improve the PDT effect of PCN-224 by mitigating hypoxia and consuming cellular GSH. Both in vitro and in vivo investigations confirmed an effective self-synergy of PAO@PCN@HA in hypoxic tumor therapy with a low systemic toxicity. This integration of microenvironment adjustment with tumor targeted self-synergistic mechanism might provide a new insight for the development of arsenic-based antitumor strategy for clinical applications.
[Display omitted]</description><subject>Anticancer properties</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antitumor agents</subject><subject>Apoptosis</subject><subject>Arsenic</subject><subject>Arsenic - therapeutic use</subject><subject>Biocompatibility</subject><subject>Biomedical materials</subject><subject>Cell Line, Tumor</subject><subject>Chemotherapy</subject><subject>Drug delivery</subject><subject>Drug Delivery Systems</subject><subject>Humans</subject><subject>Hyaluronic acid</subject><subject>Hypoxia</subject><subject>In vivo methods and tests</subject><subject>Metal-organic frameworks</subject><subject>Microenvironments</subject><subject>Neoplasms - drug therapy</subject><subject>Photochemotherapy</subject><subject>Photodynamic therapy</subject><subject>Photosensitizing Agents - therapeutic use</subject><subject>Reactive oxygen species</subject><subject>Side effects</subject><subject>Toxicity</subject><subject>Tumor Microenvironment</subject><subject>Tumors</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kD1vFDEQhq2IKAmBf4DQSjRpdhl_3NpukFBEIFKkNKGgsnz2bOLT7nqxvUjHr49PFygoaGameN6Z0UPIOwodBdp_3HXWlW2IHQMGHegOhDwhF1RJ1cpNr17VWQrWSujpOXmd8w6AK8rUGTnnHChsqLggPx7WKaam2PSIBX2TcRzavJ8xPYZcgmtmO8dltGWIacpNrY1NGefg2lpzKOF3TS1PsUS_n-1UE-UJk132b8jpYMeMb1_6Jfl-8-Xh-lt7d__19vrzXeu4htL2lispNeMenfCUO6kHBdg7vhVuEMA2fqCMoke-kdoiaumU9HbotbLMO35Jro57lxR_rpiLmUJ2OI52xrhmw4RQAqRUvKIf_kF3cU1z_a5SveyZkPpAiSPlUsw54WCWFCab9oaCOag3O3NUbw7qDWhT1dfY-5fl63ZC_zf0x3UFPh0BrDZ-BUwmu4CzQx8SumJ8DP-_8Awws5h9</recordid><startdate>202011</startdate><enddate>202011</enddate><creator>Yuan, Ping</creator><creator>Fan, Gui-Ling</creator><creator>Zhao, Lin-Ping</creator><creator>Liu, Ling-Shan</creator><creator>Deng, Fu-An</creator><creator>Jiang, Xue-Yan</creator><creator>Hu, Ai-Hua</creator><creator>Yu, Xi-Yong</creator><creator>Chen, A-Li</creator><creator>Cheng, Hong</creator><creator>Li, Shi-Ying</creator><general>Elsevier Ltd</general><general>Elsevier BV</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>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>202011</creationdate><title>Tumor targeted self-synergistic nanoplatforms for arsenic-sensitized photodynamic therapy</title><author>Yuan, Ping ; 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However, most traditional therapeutic strategies were limited due to their non-specificity and abnormal tumor microenvironments, causing a poor therapeutic efficiency and severe side effects. In this paper, a tumor targeted self-synergistic nanoplatform (designated as PAO@PCN@HA) was developed for chemotherapy sensitized photodynamic therapy (PDT) against hypoxic tumors. The efficient drug loading of phenylarsine oxide (PAO) in porphyrinic metal organic framework of PCN-224 as well as the surface modification of hyaluronic acid (HA) improved the targeted drug delivery and reduced the side effects of PAO at the therapeutic dose. Particularly, PAO as an arsenical-based chemotherapeutic agent could not only induce cell apoptosis by generating reactive oxygen species (ROS), but also regulate tumor microenvironments to improve the PDT effect of PCN-224 by mitigating hypoxia and consuming cellular GSH. Both in vitro and in vivo investigations confirmed an effective self-synergy of PAO@PCN@HA in hypoxic tumor therapy with a low systemic toxicity. This integration of microenvironment adjustment with tumor targeted self-synergistic mechanism might provide a new insight for the development of arsenic-based antitumor strategy for clinical applications.
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| subjects | Anticancer properties Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Antitumor agents Apoptosis Arsenic Arsenic - therapeutic use Biocompatibility Biomedical materials Cell Line, Tumor Chemotherapy Drug delivery Drug Delivery Systems Humans Hyaluronic acid Hypoxia In vivo methods and tests Metal-organic frameworks Microenvironments Neoplasms - drug therapy Photochemotherapy Photodynamic therapy Photosensitizing Agents - therapeutic use Reactive oxygen species Side effects Toxicity Tumor Microenvironment Tumors |
| title | Tumor targeted self-synergistic nanoplatforms for arsenic-sensitized photodynamic therapy |
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