Assembly Transformation Jointly Driven by the LAP Enzyme and GSH Boosting Theranostic Capability for Effective Tumor Therapy
Developing intelligent and morphology-transformable nanomaterials that can spatiotemporally undergo stimulus-responsive size transformation holds great promise for improving the tumor delivery efficiency of drugs . Here, we report a smart size-transformable theranostic probe Ce6-Leu consisting of a...
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| Veröffentlicht in: | ACS applied materials & interfaces 2021-12, Vol.13 (50), p.59787-59802 |
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| creator | Wang, Anna Fang, Jing Ye, Shuyue Mao, Qiulian Zhao, Yan Cui, Chaoxiang Zhang, Yuqi Feng, Yali Li, Jiachen He, Lei Qiu, Ling Shi, Haibin |
| description | Developing intelligent and morphology-transformable nanomaterials that can spatiotemporally undergo stimulus-responsive size transformation holds great promise for improving the tumor delivery efficiency of drugs
. Here, we report a smart size-transformable theranostic probe Ce6-Leu consisting of a leucine amino peptidase (LAP) and glutathione (GSH) dual-responsive moiety, an 1,2-aminothiol group, and a clinically used photosensitizer Ce6. This probe tends to self-assemble into uniform nanoparticles with an initial size of ∼80 nm in aqueous solution owing to the amphiphilic feature. Surprisingly, taking advantage of the biocompatible CBT-Cys condensation reaction, the large nanoprobes can be transformed into tiny nanoparticles (∼23 nm) under the joint action of LAP and GSH in a tumor microenvironment, endowing them with great tumor accumulation and deep tissue penetration. Concomitantly, this LAP/GSH-driven disassembly and size shrinkage of Ce6-Leu can also activate the fluorescence/magnetic resonance signals and the photodynamic effect for enhanced multimodal imaging-guided photodynamic therapy of human liver HepG2 tumors
. More excitingly, the Mn
-chelating probe (Ce6-Leu@Mn
) was demonstrated to have the capability to catalyze endogenous H
O
to persistently release O
at the hypoxic tumor site, as a consequence improving the oxygen supply to boost the radiotherapy effect. We thus believe that this LAP/GSH-driven size-transformable nanosystem would offer a novel advanced technology to improve the drug delivery efficiency for achieving precise tumor diagnosis and treatment. |
| doi_str_mv | 10.1021/acsami.1c21062 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2609468509</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2609468509</sourcerecordid><originalsourceid>FETCH-LOGICAL-c295t-44ea18854b5d1aefa8dd0ed6ce1f0941f7a6e9c9bf927c2af712b6a6586f1ee03</originalsourceid><addsrcrecordid>eNo9kDFPwzAQRi0EoqWwMiKPLCm247jJWEppQZVAIsyR45ypUZyEOEEK4sfj0sJ0953eveFD6JKSKSWM3kjlpDVTqhglgh2hMU04D2IWseP_nfMROnPunRARMhKdolHI44QLwcfoe-4c2LwccNrKyum6tbIzdYUfa1N1_nzXmk-ocD7gbgt4M3_Gy-prsIBlVeDVyxrf1rXrTPWG0y14xS4ovJCNzE1pugF7JV5qDarzIpz21udftBnO0YmWpYOLw5yg1_tlulgHm6fVw2K-CRRLoi7gHCSN44jnUUElaBkXBYFCKKCaJJzqmRSQqCTXCZspJvWMslxIEcVCUwASTtD13tu09UcPrsuscQrKUlZQ9y5jwmtEHJHEo9M9qtrauRZ01rTGynbIKMl2jWf7xrND4_7h6uDucwvFP_5XcfgDjk1_vQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2609468509</pqid></control><display><type>article</type><title>Assembly Transformation Jointly Driven by the LAP Enzyme and GSH Boosting Theranostic Capability for Effective Tumor Therapy</title><source>MEDLINE</source><source>American Chemical Society Journals</source><creator>Wang, Anna ; Fang, Jing ; Ye, Shuyue ; Mao, Qiulian ; Zhao, Yan ; Cui, Chaoxiang ; Zhang, Yuqi ; Feng, Yali ; Li, Jiachen ; He, Lei ; Qiu, Ling ; Shi, Haibin</creator><creatorcontrib>Wang, Anna ; Fang, Jing ; Ye, Shuyue ; Mao, Qiulian ; Zhao, Yan ; Cui, Chaoxiang ; Zhang, Yuqi ; Feng, Yali ; Li, Jiachen ; He, Lei ; Qiu, Ling ; Shi, Haibin</creatorcontrib><description>Developing intelligent and morphology-transformable nanomaterials that can spatiotemporally undergo stimulus-responsive size transformation holds great promise for improving the tumor delivery efficiency of drugs
. Here, we report a smart size-transformable theranostic probe Ce6-Leu consisting of a leucine amino peptidase (LAP) and glutathione (GSH) dual-responsive moiety, an 1,2-aminothiol group, and a clinically used photosensitizer Ce6. This probe tends to self-assemble into uniform nanoparticles with an initial size of ∼80 nm in aqueous solution owing to the amphiphilic feature. Surprisingly, taking advantage of the biocompatible CBT-Cys condensation reaction, the large nanoprobes can be transformed into tiny nanoparticles (∼23 nm) under the joint action of LAP and GSH in a tumor microenvironment, endowing them with great tumor accumulation and deep tissue penetration. Concomitantly, this LAP/GSH-driven disassembly and size shrinkage of Ce6-Leu can also activate the fluorescence/magnetic resonance signals and the photodynamic effect for enhanced multimodal imaging-guided photodynamic therapy of human liver HepG2 tumors
. More excitingly, the Mn
-chelating probe (Ce6-Leu@Mn
) was demonstrated to have the capability to catalyze endogenous H
O
to persistently release O
at the hypoxic tumor site, as a consequence improving the oxygen supply to boost the radiotherapy effect. We thus believe that this LAP/GSH-driven size-transformable nanosystem would offer a novel advanced technology to improve the drug delivery efficiency for achieving precise tumor diagnosis and treatment.</description><identifier>ISSN: 1944-8244</identifier><identifier>EISSN: 1944-8252</identifier><identifier>DOI: 10.1021/acsami.1c21062</identifier><identifier>PMID: 34894664</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Biocompatible Materials - chemical synthesis ; Biocompatible Materials - chemistry ; Biocompatible Materials - pharmacology ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Chlorophyllides - chemistry ; Chlorophyllides - pharmacology ; Drug Screening Assays, Antitumor ; Glutathione - metabolism ; Hep G2 Cells ; Humans ; Leucyl Aminopeptidase - metabolism ; Liver Neoplasms, Experimental - drug therapy ; Liver Neoplasms, Experimental - metabolism ; Liver Neoplasms, Experimental - pathology ; Materials Testing ; Molecular Structure ; Optical Imaging ; Particle Size ; Photochemotherapy ; Photosensitizing Agents - chemistry ; Photosensitizing Agents - pharmacology ; Theranostic Nanomedicine</subject><ispartof>ACS applied materials & interfaces, 2021-12, Vol.13 (50), p.59787-59802</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c295t-44ea18854b5d1aefa8dd0ed6ce1f0941f7a6e9c9bf927c2af712b6a6586f1ee03</citedby><cites>FETCH-LOGICAL-c295t-44ea18854b5d1aefa8dd0ed6ce1f0941f7a6e9c9bf927c2af712b6a6586f1ee03</cites><orcidid>0000-0003-2234-9126</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2765,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34894664$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Anna</creatorcontrib><creatorcontrib>Fang, Jing</creatorcontrib><creatorcontrib>Ye, Shuyue</creatorcontrib><creatorcontrib>Mao, Qiulian</creatorcontrib><creatorcontrib>Zhao, Yan</creatorcontrib><creatorcontrib>Cui, Chaoxiang</creatorcontrib><creatorcontrib>Zhang, Yuqi</creatorcontrib><creatorcontrib>Feng, Yali</creatorcontrib><creatorcontrib>Li, Jiachen</creatorcontrib><creatorcontrib>He, Lei</creatorcontrib><creatorcontrib>Qiu, Ling</creatorcontrib><creatorcontrib>Shi, Haibin</creatorcontrib><title>Assembly Transformation Jointly Driven by the LAP Enzyme and GSH Boosting Theranostic Capability for Effective Tumor Therapy</title><title>ACS applied materials & interfaces</title><addtitle>ACS Appl Mater Interfaces</addtitle><description>Developing intelligent and morphology-transformable nanomaterials that can spatiotemporally undergo stimulus-responsive size transformation holds great promise for improving the tumor delivery efficiency of drugs
. Here, we report a smart size-transformable theranostic probe Ce6-Leu consisting of a leucine amino peptidase (LAP) and glutathione (GSH) dual-responsive moiety, an 1,2-aminothiol group, and a clinically used photosensitizer Ce6. This probe tends to self-assemble into uniform nanoparticles with an initial size of ∼80 nm in aqueous solution owing to the amphiphilic feature. Surprisingly, taking advantage of the biocompatible CBT-Cys condensation reaction, the large nanoprobes can be transformed into tiny nanoparticles (∼23 nm) under the joint action of LAP and GSH in a tumor microenvironment, endowing them with great tumor accumulation and deep tissue penetration. Concomitantly, this LAP/GSH-driven disassembly and size shrinkage of Ce6-Leu can also activate the fluorescence/magnetic resonance signals and the photodynamic effect for enhanced multimodal imaging-guided photodynamic therapy of human liver HepG2 tumors
. More excitingly, the Mn
-chelating probe (Ce6-Leu@Mn
) was demonstrated to have the capability to catalyze endogenous H
O
to persistently release O
at the hypoxic tumor site, as a consequence improving the oxygen supply to boost the radiotherapy effect. We thus believe that this LAP/GSH-driven size-transformable nanosystem would offer a novel advanced technology to improve the drug delivery efficiency for achieving precise tumor diagnosis and treatment.</description><subject>Animals</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biocompatible Materials - chemical synthesis</subject><subject>Biocompatible Materials - chemistry</subject><subject>Biocompatible Materials - pharmacology</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Chlorophyllides - chemistry</subject><subject>Chlorophyllides - pharmacology</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Glutathione - metabolism</subject><subject>Hep G2 Cells</subject><subject>Humans</subject><subject>Leucyl Aminopeptidase - metabolism</subject><subject>Liver Neoplasms, Experimental - drug therapy</subject><subject>Liver Neoplasms, Experimental - metabolism</subject><subject>Liver Neoplasms, Experimental - pathology</subject><subject>Materials Testing</subject><subject>Molecular Structure</subject><subject>Optical Imaging</subject><subject>Particle Size</subject><subject>Photochemotherapy</subject><subject>Photosensitizing Agents - chemistry</subject><subject>Photosensitizing Agents - pharmacology</subject><subject>Theranostic Nanomedicine</subject><issn>1944-8244</issn><issn>1944-8252</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kDFPwzAQRi0EoqWwMiKPLCm247jJWEppQZVAIsyR45ypUZyEOEEK4sfj0sJ0953eveFD6JKSKSWM3kjlpDVTqhglgh2hMU04D2IWseP_nfMROnPunRARMhKdolHI44QLwcfoe-4c2LwccNrKyum6tbIzdYUfa1N1_nzXmk-ocD7gbgt4M3_Gy-prsIBlVeDVyxrf1rXrTPWG0y14xS4ovJCNzE1pugF7JV5qDarzIpz21udftBnO0YmWpYOLw5yg1_tlulgHm6fVw2K-CRRLoi7gHCSN44jnUUElaBkXBYFCKKCaJJzqmRSQqCTXCZspJvWMslxIEcVCUwASTtD13tu09UcPrsuscQrKUlZQ9y5jwmtEHJHEo9M9qtrauRZ01rTGynbIKMl2jWf7xrND4_7h6uDucwvFP_5XcfgDjk1_vQ</recordid><startdate>20211222</startdate><enddate>20211222</enddate><creator>Wang, Anna</creator><creator>Fang, Jing</creator><creator>Ye, Shuyue</creator><creator>Mao, Qiulian</creator><creator>Zhao, Yan</creator><creator>Cui, Chaoxiang</creator><creator>Zhang, Yuqi</creator><creator>Feng, Yali</creator><creator>Li, Jiachen</creator><creator>He, Lei</creator><creator>Qiu, Ling</creator><creator>Shi, Haibin</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><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2234-9126</orcidid></search><sort><creationdate>20211222</creationdate><title>Assembly Transformation Jointly Driven by the LAP Enzyme and GSH Boosting Theranostic Capability for Effective Tumor Therapy</title><author>Wang, Anna ; Fang, Jing ; Ye, Shuyue ; Mao, Qiulian ; Zhao, Yan ; Cui, Chaoxiang ; Zhang, Yuqi ; Feng, Yali ; Li, Jiachen ; He, Lei ; Qiu, Ling ; Shi, Haibin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c295t-44ea18854b5d1aefa8dd0ed6ce1f0941f7a6e9c9bf927c2af712b6a6586f1ee03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biocompatible Materials - chemical synthesis</topic><topic>Biocompatible Materials - chemistry</topic><topic>Biocompatible Materials - pharmacology</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Chlorophyllides - chemistry</topic><topic>Chlorophyllides - pharmacology</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Glutathione - metabolism</topic><topic>Hep G2 Cells</topic><topic>Humans</topic><topic>Leucyl Aminopeptidase - metabolism</topic><topic>Liver Neoplasms, Experimental - drug therapy</topic><topic>Liver Neoplasms, Experimental - metabolism</topic><topic>Liver Neoplasms, Experimental - pathology</topic><topic>Materials Testing</topic><topic>Molecular Structure</topic><topic>Optical Imaging</topic><topic>Particle Size</topic><topic>Photochemotherapy</topic><topic>Photosensitizing Agents - chemistry</topic><topic>Photosensitizing Agents - pharmacology</topic><topic>Theranostic Nanomedicine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Anna</creatorcontrib><creatorcontrib>Fang, Jing</creatorcontrib><creatorcontrib>Ye, Shuyue</creatorcontrib><creatorcontrib>Mao, Qiulian</creatorcontrib><creatorcontrib>Zhao, Yan</creatorcontrib><creatorcontrib>Cui, Chaoxiang</creatorcontrib><creatorcontrib>Zhang, Yuqi</creatorcontrib><creatorcontrib>Feng, Yali</creatorcontrib><creatorcontrib>Li, Jiachen</creatorcontrib><creatorcontrib>He, Lei</creatorcontrib><creatorcontrib>Qiu, Ling</creatorcontrib><creatorcontrib>Shi, Haibin</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>ACS applied materials & interfaces</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Anna</au><au>Fang, Jing</au><au>Ye, Shuyue</au><au>Mao, Qiulian</au><au>Zhao, Yan</au><au>Cui, Chaoxiang</au><au>Zhang, Yuqi</au><au>Feng, Yali</au><au>Li, Jiachen</au><au>He, Lei</au><au>Qiu, Ling</au><au>Shi, Haibin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Assembly Transformation Jointly Driven by the LAP Enzyme and GSH Boosting Theranostic Capability for Effective Tumor Therapy</atitle><jtitle>ACS applied materials & interfaces</jtitle><addtitle>ACS Appl Mater Interfaces</addtitle><date>2021-12-22</date><risdate>2021</risdate><volume>13</volume><issue>50</issue><spage>59787</spage><epage>59802</epage><pages>59787-59802</pages><issn>1944-8244</issn><eissn>1944-8252</eissn><abstract>Developing intelligent and morphology-transformable nanomaterials that can spatiotemporally undergo stimulus-responsive size transformation holds great promise for improving the tumor delivery efficiency of drugs
. Here, we report a smart size-transformable theranostic probe Ce6-Leu consisting of a leucine amino peptidase (LAP) and glutathione (GSH) dual-responsive moiety, an 1,2-aminothiol group, and a clinically used photosensitizer Ce6. This probe tends to self-assemble into uniform nanoparticles with an initial size of ∼80 nm in aqueous solution owing to the amphiphilic feature. Surprisingly, taking advantage of the biocompatible CBT-Cys condensation reaction, the large nanoprobes can be transformed into tiny nanoparticles (∼23 nm) under the joint action of LAP and GSH in a tumor microenvironment, endowing them with great tumor accumulation and deep tissue penetration. Concomitantly, this LAP/GSH-driven disassembly and size shrinkage of Ce6-Leu can also activate the fluorescence/magnetic resonance signals and the photodynamic effect for enhanced multimodal imaging-guided photodynamic therapy of human liver HepG2 tumors
. More excitingly, the Mn
-chelating probe (Ce6-Leu@Mn
) was demonstrated to have the capability to catalyze endogenous H
O
to persistently release O
at the hypoxic tumor site, as a consequence improving the oxygen supply to boost the radiotherapy effect. We thus believe that this LAP/GSH-driven size-transformable nanosystem would offer a novel advanced technology to improve the drug delivery efficiency for achieving precise tumor diagnosis and treatment.</abstract><cop>United States</cop><pmid>34894664</pmid><doi>10.1021/acsami.1c21062</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0003-2234-9126</orcidid></addata></record> |
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| subjects | Animals Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Biocompatible Materials - chemical synthesis Biocompatible Materials - chemistry Biocompatible Materials - pharmacology Cell Proliferation - drug effects Cell Survival - drug effects Chlorophyllides - chemistry Chlorophyllides - pharmacology Drug Screening Assays, Antitumor Glutathione - metabolism Hep G2 Cells Humans Leucyl Aminopeptidase - metabolism Liver Neoplasms, Experimental - drug therapy Liver Neoplasms, Experimental - metabolism Liver Neoplasms, Experimental - pathology Materials Testing Molecular Structure Optical Imaging Particle Size Photochemotherapy Photosensitizing Agents - chemistry Photosensitizing Agents - pharmacology Theranostic Nanomedicine |
| title | Assembly Transformation Jointly Driven by the LAP Enzyme and GSH Boosting Theranostic Capability for Effective Tumor Therapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T10%3A42%3A58IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Assembly%20Transformation%20Jointly%20Driven%20by%20the%20LAP%20Enzyme%20and%20GSH%20Boosting%20Theranostic%20Capability%20for%20Effective%20Tumor%20Therapy&rft.jtitle=ACS%20applied%20materials%20&%20interfaces&rft.au=Wang,%20Anna&rft.date=2021-12-22&rft.volume=13&rft.issue=50&rft.spage=59787&rft.epage=59802&rft.pages=59787-59802&rft.issn=1944-8244&rft.eissn=1944-8252&rft_id=info:doi/10.1021/acsami.1c21062&rft_dat=%3Cproquest_cross%3E2609468509%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2609468509&rft_id=info:pmid/34894664&rfr_iscdi=true |