Y 1 -receptor-ligand-functionalized ultrasmall upconversion nanoparticles for tumor-targeted trimodality imaging and photodynamic therapy with low toxicity
Achieving efficient photodynamic therapy (PDT) in deeper biological tissue is still the biggest bottleneck that limits its widespread application in clinic. Although deeper biological tissue PDT could be realized through a combination of upconversion nanoparticles with a photosensitizer, issues with...
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Veröffentlicht in: | Nanoscale 2018-09, Vol.10 (36), p.17038-17052 |
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creator | Yu, Zhangsen Xia, Yuanzhi Xing, Jie Li, Zihou Zhen, Jianjun Jin, Yinhua Tian, Yuchen Liu, Chuang Jiang, Zhenqi Li, Juan Wu, Aiguo |
description | Achieving efficient photodynamic therapy (PDT) in deeper biological tissue is still the biggest bottleneck that limits its widespread application in clinic. Although deeper biological tissue PDT could be realized through a combination of upconversion nanoparticles with a photosensitizer, issues with particle-size-induced upconversion fluorescence (UF) reduction and the related in vivo toxicity still cannot be solved properly. In this study, we synthesized Y1Rs-ligand [Pro30, Nle31, Bpa32, Leu34]NPY(28-36) (NPY)-modified and photosensitizer MC540-loaded LiLuF4:Yb,Er@nLiGdF4@mSiO2 multifunctional nanocomposites (MNPs) with a core-multishell structure and ultrasmall size. Their in vitro and in vivo breast tumor targeting, trimodality imaging performance, PDT therapeutic efficacy, and acute toxicity were evaluated. Our results demonstrated that the core-multishell MNPs(MC540) could achieve excellent UF imaging, and that doping with Gd3+ and Lu3+ rare earth ions could enhance the MR and CT imaging performance. In addition, the mSiO2 shell provided a higher loading rate for the photosensitizer MC540, and the DSPE-PEG thin layer coating outside the MNPs(MC540) further improved the water solubility and biocompatibility, reducing the acute toxicity of the nanocomposites. Finally, the NPY modification enhanced the targetability of MNPs(MC540)/DSPE-PEG-NPY to breast tumors, improving the trimodality UF, CT, and MR imaging performance and PDT efficacy for Y1-receptor-overexpressed breast cancer. In general, our developed multifunctional nanocomposites can serve as a theranostic agent with low toxicity, providing great potential for their use in clinical breast cancer diagnosis and therapy. |
doi_str_mv | 10.1039/C8NR02387E |
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Although deeper biological tissue PDT could be realized through a combination of upconversion nanoparticles with a photosensitizer, issues with particle-size-induced upconversion fluorescence (UF) reduction and the related in vivo toxicity still cannot be solved properly. In this study, we synthesized Y1Rs-ligand [Pro30, Nle31, Bpa32, Leu34]NPY(28-36) (NPY)-modified and photosensitizer MC540-loaded LiLuF4:Yb,Er@nLiGdF4@mSiO2 multifunctional nanocomposites (MNPs) with a core-multishell structure and ultrasmall size. Their in vitro and in vivo breast tumor targeting, trimodality imaging performance, PDT therapeutic efficacy, and acute toxicity were evaluated. Our results demonstrated that the core-multishell MNPs(MC540) could achieve excellent UF imaging, and that doping with Gd3+ and Lu3+ rare earth ions could enhance the MR and CT imaging performance. In addition, the mSiO2 shell provided a higher loading rate for the photosensitizer MC540, and the DSPE-PEG thin layer coating outside the MNPs(MC540) further improved the water solubility and biocompatibility, reducing the acute toxicity of the nanocomposites. Finally, the NPY modification enhanced the targetability of MNPs(MC540)/DSPE-PEG-NPY to breast tumors, improving the trimodality UF, CT, and MR imaging performance and PDT efficacy for Y1-receptor-overexpressed breast cancer. In general, our developed multifunctional nanocomposites can serve as a theranostic agent with low toxicity, providing great potential for their use in clinical breast cancer diagnosis and therapy.</description><identifier>ISSN: 2040-3364</identifier><identifier>EISSN: 2040-3372</identifier><identifier>DOI: 10.1039/C8NR02387E</identifier><identifier>PMID: 29850734</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Cell Line, Tumor ; Female ; Humans ; MCF-7 Cells ; Mice, Inbred BALB C ; Mice, Inbred ICR ; Nanocomposites - chemistry ; Nanoparticles - chemistry ; Neoplasms, Experimental - drug therapy ; Photochemotherapy ; Photosensitizing Agents - pharmacology ; Xenograft Model Antitumor Assays</subject><ispartof>Nanoscale, 2018-09, Vol.10 (36), p.17038-17052</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c994-27ec83247839e492025ba65b66e5b72dcff6095beab9979214b68471984737653</citedby><cites>FETCH-LOGICAL-c994-27ec83247839e492025ba65b66e5b72dcff6095beab9979214b68471984737653</cites><orcidid>0000-0001-7200-8923</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29850734$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Zhangsen</creatorcontrib><creatorcontrib>Xia, Yuanzhi</creatorcontrib><creatorcontrib>Xing, Jie</creatorcontrib><creatorcontrib>Li, Zihou</creatorcontrib><creatorcontrib>Zhen, Jianjun</creatorcontrib><creatorcontrib>Jin, Yinhua</creatorcontrib><creatorcontrib>Tian, Yuchen</creatorcontrib><creatorcontrib>Liu, Chuang</creatorcontrib><creatorcontrib>Jiang, Zhenqi</creatorcontrib><creatorcontrib>Li, Juan</creatorcontrib><creatorcontrib>Wu, Aiguo</creatorcontrib><title>Y 1 -receptor-ligand-functionalized ultrasmall upconversion nanoparticles for tumor-targeted trimodality imaging and photodynamic therapy with low toxicity</title><title>Nanoscale</title><addtitle>Nanoscale</addtitle><description>Achieving efficient photodynamic therapy (PDT) in deeper biological tissue is still the biggest bottleneck that limits its widespread application in clinic. Although deeper biological tissue PDT could be realized through a combination of upconversion nanoparticles with a photosensitizer, issues with particle-size-induced upconversion fluorescence (UF) reduction and the related in vivo toxicity still cannot be solved properly. In this study, we synthesized Y1Rs-ligand [Pro30, Nle31, Bpa32, Leu34]NPY(28-36) (NPY)-modified and photosensitizer MC540-loaded LiLuF4:Yb,Er@nLiGdF4@mSiO2 multifunctional nanocomposites (MNPs) with a core-multishell structure and ultrasmall size. Their in vitro and in vivo breast tumor targeting, trimodality imaging performance, PDT therapeutic efficacy, and acute toxicity were evaluated. Our results demonstrated that the core-multishell MNPs(MC540) could achieve excellent UF imaging, and that doping with Gd3+ and Lu3+ rare earth ions could enhance the MR and CT imaging performance. In addition, the mSiO2 shell provided a higher loading rate for the photosensitizer MC540, and the DSPE-PEG thin layer coating outside the MNPs(MC540) further improved the water solubility and biocompatibility, reducing the acute toxicity of the nanocomposites. Finally, the NPY modification enhanced the targetability of MNPs(MC540)/DSPE-PEG-NPY to breast tumors, improving the trimodality UF, CT, and MR imaging performance and PDT efficacy for Y1-receptor-overexpressed breast cancer. In general, our developed multifunctional nanocomposites can serve as a theranostic agent with low toxicity, providing great potential for their use in clinical breast cancer diagnosis and therapy.</description><subject>Animals</subject><subject>Cell Line, Tumor</subject><subject>Female</subject><subject>Humans</subject><subject>MCF-7 Cells</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred ICR</subject><subject>Nanocomposites - chemistry</subject><subject>Nanoparticles - chemistry</subject><subject>Neoplasms, Experimental - drug therapy</subject><subject>Photochemotherapy</subject><subject>Photosensitizing Agents - pharmacology</subject><subject>Xenograft Model Antitumor Assays</subject><issn>2040-3364</issn><issn>2040-3372</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM1KxDAUhYMozji68QEka6GaJm3SLGUYf2BQkNm4KmmadiJpU5LUsb6KL2tk_Nnce-Ge83E4AJyn6CpFhF8vi8dnhEnBVgdgjlGGEkIYPvy7aTYDJ96_IkQ5oeQYzDAvcsRINgefLzCFiVNSDcG6xOhW9HXSjL0M2vbC6A9Vw9EEJ3wnjIHjIG3_ppyPX9iL3g7CBS2N8rCxDoaxi5QgXKtCNAanO1tHSpig7kSr-xZGPhy2Nth66kWnJQxb5cQwwZ0OW2jsDgb7rmW0nIKjRhivzn72AmxuV5vlfbJ-untY3qwTyXmWYKZkQXDGCsJVxjHCeSVoXlGq8orhWjYNRTyvlKg4ZxynWUWLjKU8DsJoThbgco-VznrvVFMOMbZwU5mi8rvg8r_gKL7Yi4ex6lT9J_1tlHwByLF6Cg</recordid><startdate>20180920</startdate><enddate>20180920</enddate><creator>Yu, Zhangsen</creator><creator>Xia, Yuanzhi</creator><creator>Xing, Jie</creator><creator>Li, Zihou</creator><creator>Zhen, Jianjun</creator><creator>Jin, Yinhua</creator><creator>Tian, Yuchen</creator><creator>Liu, Chuang</creator><creator>Jiang, Zhenqi</creator><creator>Li, Juan</creator><creator>Wu, Aiguo</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0001-7200-8923</orcidid></search><sort><creationdate>20180920</creationdate><title>Y 1 -receptor-ligand-functionalized ultrasmall upconversion nanoparticles for tumor-targeted trimodality imaging and photodynamic therapy with low toxicity</title><author>Yu, Zhangsen ; Xia, Yuanzhi ; Xing, Jie ; Li, Zihou ; Zhen, Jianjun ; Jin, Yinhua ; Tian, Yuchen ; Liu, Chuang ; Jiang, Zhenqi ; Li, Juan ; Wu, Aiguo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c994-27ec83247839e492025ba65b66e5b72dcff6095beab9979214b68471984737653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Cell Line, Tumor</topic><topic>Female</topic><topic>Humans</topic><topic>MCF-7 Cells</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred ICR</topic><topic>Nanocomposites - chemistry</topic><topic>Nanoparticles - chemistry</topic><topic>Neoplasms, Experimental - drug therapy</topic><topic>Photochemotherapy</topic><topic>Photosensitizing Agents - pharmacology</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Zhangsen</creatorcontrib><creatorcontrib>Xia, Yuanzhi</creatorcontrib><creatorcontrib>Xing, Jie</creatorcontrib><creatorcontrib>Li, Zihou</creatorcontrib><creatorcontrib>Zhen, Jianjun</creatorcontrib><creatorcontrib>Jin, Yinhua</creatorcontrib><creatorcontrib>Tian, Yuchen</creatorcontrib><creatorcontrib>Liu, Chuang</creatorcontrib><creatorcontrib>Jiang, Zhenqi</creatorcontrib><creatorcontrib>Li, Juan</creatorcontrib><creatorcontrib>Wu, Aiguo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Nanoscale</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Zhangsen</au><au>Xia, Yuanzhi</au><au>Xing, Jie</au><au>Li, Zihou</au><au>Zhen, Jianjun</au><au>Jin, Yinhua</au><au>Tian, Yuchen</au><au>Liu, Chuang</au><au>Jiang, Zhenqi</au><au>Li, Juan</au><au>Wu, Aiguo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Y 1 -receptor-ligand-functionalized ultrasmall upconversion nanoparticles for tumor-targeted trimodality imaging and photodynamic therapy with low toxicity</atitle><jtitle>Nanoscale</jtitle><addtitle>Nanoscale</addtitle><date>2018-09-20</date><risdate>2018</risdate><volume>10</volume><issue>36</issue><spage>17038</spage><epage>17052</epage><pages>17038-17052</pages><issn>2040-3364</issn><eissn>2040-3372</eissn><abstract>Achieving efficient photodynamic therapy (PDT) in deeper biological tissue is still the biggest bottleneck that limits its widespread application in clinic. Although deeper biological tissue PDT could be realized through a combination of upconversion nanoparticles with a photosensitizer, issues with particle-size-induced upconversion fluorescence (UF) reduction and the related in vivo toxicity still cannot be solved properly. In this study, we synthesized Y1Rs-ligand [Pro30, Nle31, Bpa32, Leu34]NPY(28-36) (NPY)-modified and photosensitizer MC540-loaded LiLuF4:Yb,Er@nLiGdF4@mSiO2 multifunctional nanocomposites (MNPs) with a core-multishell structure and ultrasmall size. Their in vitro and in vivo breast tumor targeting, trimodality imaging performance, PDT therapeutic efficacy, and acute toxicity were evaluated. Our results demonstrated that the core-multishell MNPs(MC540) could achieve excellent UF imaging, and that doping with Gd3+ and Lu3+ rare earth ions could enhance the MR and CT imaging performance. In addition, the mSiO2 shell provided a higher loading rate for the photosensitizer MC540, and the DSPE-PEG thin layer coating outside the MNPs(MC540) further improved the water solubility and biocompatibility, reducing the acute toxicity of the nanocomposites. Finally, the NPY modification enhanced the targetability of MNPs(MC540)/DSPE-PEG-NPY to breast tumors, improving the trimodality UF, CT, and MR imaging performance and PDT efficacy for Y1-receptor-overexpressed breast cancer. In general, our developed multifunctional nanocomposites can serve as a theranostic agent with low toxicity, providing great potential for their use in clinical breast cancer diagnosis and therapy.</abstract><cop>England</cop><pmid>29850734</pmid><doi>10.1039/C8NR02387E</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0001-7200-8923</orcidid></addata></record> |
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subjects | Animals Cell Line, Tumor Female Humans MCF-7 Cells Mice, Inbred BALB C Mice, Inbred ICR Nanocomposites - chemistry Nanoparticles - chemistry Neoplasms, Experimental - drug therapy Photochemotherapy Photosensitizing Agents - pharmacology Xenograft Model Antitumor Assays |
title | Y 1 -receptor-ligand-functionalized ultrasmall upconversion nanoparticles for tumor-targeted trimodality imaging and photodynamic therapy with low toxicity |
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