Coordination of rigidity modulation and targeting ligand modification on orally-delivered nanoparticles for the treatment of liver fibrosis

Although the individual role of ligand modification or rigidity modulation on oral administration of nanoparticle (NP) has been investigated, how they mutually affect each other remains to be elucidated. Here, we fabricated different rigidity NP with or without surface decoration of FcBP, a neonatal...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of controlled release 2022-01, Vol.341, p.215-226
Hauptverfasser: Yu, Yinglan, Xing, LiYun, Li, Lian, Wu, Jiawei, He, Jinhan, Huang, Yuan
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 226
container_issue
container_start_page 215
container_title Journal of controlled release
container_volume 341
creator Yu, Yinglan
Xing, LiYun
Li, Lian
Wu, Jiawei
He, Jinhan
Huang, Yuan
description Although the individual role of ligand modification or rigidity modulation on oral administration of nanoparticle (NP) has been investigated, how they mutually affect each other remains to be elucidated. Here, we fabricated different rigidity NP with or without surface decoration of FcBP, a neonatal Fc receptor domain-binding peptide. In vitro studies showed that, without FcBP modification, stiff NP had higher transcytosis efficiency across the epithelium than softer NP, due to the different endocytosis mechanisms, intracellular trafficking routes, and exocytosis rate. Notably, after FcBP modification, such difference was narrowed, in a manner that was more favorable for softer NP to “catch up” with stiff NP, suggesting ligand modification was more conducive to exert transcytosis-promoting efficacy on softer NP. In vivo experiments demonstrated that, for ligand-free NP, high rigidity was required for efficient oral absorption and liver distribution. Further FcBP modification decreased that “rigidity threshold”, and expanded the feasible rigidity range from stiff NP to softer NP. Upon oral administration, FcBP-modified dexamethasone-loaded softer NP achieved a therapeutic efficacy comparable with stiff NP on alleviating liver fibrosis. Collectively, our study highlighted the necessity of coordinating ligand modification and rigidity modulation for oral drug delivery. We fabricated different rigidity NP with or without surface decoration of FcBP, a neonatal Fc receptor domain-binding peptide. Our results revealed that ligand-free NP, high rigidity was required for efficient oral absorption. Further FcBP modification decreased that “rigidity threshold”, and expanded the feasible rigidity range from stiff NP to softer NP. [Display omitted] •Ligand endowed nanocarriers with the ability of active-targeting.•The rigidity of ligand-modified NP would regulate receptor-mediated transcytosis.•Ligand broadened the range of feasible rigidity.
doi_str_mv 10.1016/j.jconrel.2021.11.026
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2604016576</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0168365921006210</els_id><sourcerecordid>2604016576</sourcerecordid><originalsourceid>FETCH-LOGICAL-c365t-83a49d2c910c6e940d6ac14112cb80591d93f57728cdbd90495dc71c6d1786223</originalsourceid><addsrcrecordid>eNqFkcFuEzEQhi1ERdOWRwD5yGUX27vrXZ8QigpUqsSFni3Hng0Tee1gO5XyDLx0HRK4IlmyNP5-_zPzE_KOs5YzLj_u2p2NIYFvBRO85bxlQr4iKz6NXdMrNbwmq8pNTScHdU1uct4xxoauH9-Q666fhFBsWpHf6xiTw2AKxkDjTBNu0WE50iW6gz-XTXC0mLSFgmFLPW5PhfqOM9qLsJ5kvD82Djw-QwJHgwlxb1JB6yHTOSZafgItCUxZIJST2R-UzrhJMWO-I1ez8RneXu5b8vTl_sf6W_P4_evD-vNjY-sspZk60ysnrOLMSlA9c9JY3nMu7GZig-JOdfMwjmKybuMU69Xg7MitdHycpBDdLflw_nef4q8D5KIXzBa8NwHiIWshWV9XN4yyosMZtbXDnGDW-4SLSUfNmT7loHf6koM-5aA51zWHqnt_sThsFnD_VH8XX4FPZwDqoM8ISWeLECw4TGCLdhH_Y_EC6amfQw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2604016576</pqid></control><display><type>article</type><title>Coordination of rigidity modulation and targeting ligand modification on orally-delivered nanoparticles for the treatment of liver fibrosis</title><source>Access via ScienceDirect (Elsevier)</source><creator>Yu, Yinglan ; Xing, LiYun ; Li, Lian ; Wu, Jiawei ; He, Jinhan ; Huang, Yuan</creator><creatorcontrib>Yu, Yinglan ; Xing, LiYun ; Li, Lian ; Wu, Jiawei ; He, Jinhan ; Huang, Yuan</creatorcontrib><description>Although the individual role of ligand modification or rigidity modulation on oral administration of nanoparticle (NP) has been investigated, how they mutually affect each other remains to be elucidated. Here, we fabricated different rigidity NP with or without surface decoration of FcBP, a neonatal Fc receptor domain-binding peptide. In vitro studies showed that, without FcBP modification, stiff NP had higher transcytosis efficiency across the epithelium than softer NP, due to the different endocytosis mechanisms, intracellular trafficking routes, and exocytosis rate. Notably, after FcBP modification, such difference was narrowed, in a manner that was more favorable for softer NP to “catch up” with stiff NP, suggesting ligand modification was more conducive to exert transcytosis-promoting efficacy on softer NP. In vivo experiments demonstrated that, for ligand-free NP, high rigidity was required for efficient oral absorption and liver distribution. Further FcBP modification decreased that “rigidity threshold”, and expanded the feasible rigidity range from stiff NP to softer NP. Upon oral administration, FcBP-modified dexamethasone-loaded softer NP achieved a therapeutic efficacy comparable with stiff NP on alleviating liver fibrosis. Collectively, our study highlighted the necessity of coordinating ligand modification and rigidity modulation for oral drug delivery. We fabricated different rigidity NP with or without surface decoration of FcBP, a neonatal Fc receptor domain-binding peptide. Our results revealed that ligand-free NP, high rigidity was required for efficient oral absorption. Further FcBP modification decreased that “rigidity threshold”, and expanded the feasible rigidity range from stiff NP to softer NP. [Display omitted] •Ligand endowed nanocarriers with the ability of active-targeting.•The rigidity of ligand-modified NP would regulate receptor-mediated transcytosis.•Ligand broadened the range of feasible rigidity.</description><identifier>ISSN: 0168-3659</identifier><identifier>EISSN: 1873-4995</identifier><identifier>DOI: 10.1016/j.jconrel.2021.11.026</identifier><identifier>PMID: 34822908</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Epithelial barrier ; FcBP modification ; Liver fibrosis ; Mucus barrier ; Oral absorption ; Rigidity</subject><ispartof>Journal of controlled release, 2022-01, Vol.341, p.215-226</ispartof><rights>2021 Elsevier B.V.</rights><rights>Copyright © 2021 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-83a49d2c910c6e940d6ac14112cb80591d93f57728cdbd90495dc71c6d1786223</citedby><cites>FETCH-LOGICAL-c365t-83a49d2c910c6e940d6ac14112cb80591d93f57728cdbd90495dc71c6d1786223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jconrel.2021.11.026$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34822908$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Yinglan</creatorcontrib><creatorcontrib>Xing, LiYun</creatorcontrib><creatorcontrib>Li, Lian</creatorcontrib><creatorcontrib>Wu, Jiawei</creatorcontrib><creatorcontrib>He, Jinhan</creatorcontrib><creatorcontrib>Huang, Yuan</creatorcontrib><title>Coordination of rigidity modulation and targeting ligand modification on orally-delivered nanoparticles for the treatment of liver fibrosis</title><title>Journal of controlled release</title><addtitle>J Control Release</addtitle><description>Although the individual role of ligand modification or rigidity modulation on oral administration of nanoparticle (NP) has been investigated, how they mutually affect each other remains to be elucidated. Here, we fabricated different rigidity NP with or without surface decoration of FcBP, a neonatal Fc receptor domain-binding peptide. In vitro studies showed that, without FcBP modification, stiff NP had higher transcytosis efficiency across the epithelium than softer NP, due to the different endocytosis mechanisms, intracellular trafficking routes, and exocytosis rate. Notably, after FcBP modification, such difference was narrowed, in a manner that was more favorable for softer NP to “catch up” with stiff NP, suggesting ligand modification was more conducive to exert transcytosis-promoting efficacy on softer NP. In vivo experiments demonstrated that, for ligand-free NP, high rigidity was required for efficient oral absorption and liver distribution. Further FcBP modification decreased that “rigidity threshold”, and expanded the feasible rigidity range from stiff NP to softer NP. Upon oral administration, FcBP-modified dexamethasone-loaded softer NP achieved a therapeutic efficacy comparable with stiff NP on alleviating liver fibrosis. Collectively, our study highlighted the necessity of coordinating ligand modification and rigidity modulation for oral drug delivery. We fabricated different rigidity NP with or without surface decoration of FcBP, a neonatal Fc receptor domain-binding peptide. Our results revealed that ligand-free NP, high rigidity was required for efficient oral absorption. Further FcBP modification decreased that “rigidity threshold”, and expanded the feasible rigidity range from stiff NP to softer NP. [Display omitted] •Ligand endowed nanocarriers with the ability of active-targeting.•The rigidity of ligand-modified NP would regulate receptor-mediated transcytosis.•Ligand broadened the range of feasible rigidity.</description><subject>Epithelial barrier</subject><subject>FcBP modification</subject><subject>Liver fibrosis</subject><subject>Mucus barrier</subject><subject>Oral absorption</subject><subject>Rigidity</subject><issn>0168-3659</issn><issn>1873-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNqFkcFuEzEQhi1ERdOWRwD5yGUX27vrXZ8QigpUqsSFni3Hng0Tee1gO5XyDLx0HRK4IlmyNP5-_zPzE_KOs5YzLj_u2p2NIYFvBRO85bxlQr4iKz6NXdMrNbwmq8pNTScHdU1uct4xxoauH9-Q666fhFBsWpHf6xiTw2AKxkDjTBNu0WE50iW6gz-XTXC0mLSFgmFLPW5PhfqOM9qLsJ5kvD82Djw-QwJHgwlxb1JB6yHTOSZafgItCUxZIJST2R-UzrhJMWO-I1ez8RneXu5b8vTl_sf6W_P4_evD-vNjY-sspZk60ysnrOLMSlA9c9JY3nMu7GZig-JOdfMwjmKybuMU69Xg7MitdHycpBDdLflw_nef4q8D5KIXzBa8NwHiIWshWV9XN4yyosMZtbXDnGDW-4SLSUfNmT7loHf6koM-5aA51zWHqnt_sThsFnD_VH8XX4FPZwDqoM8ISWeLECw4TGCLdhH_Y_EC6amfQw</recordid><startdate>202201</startdate><enddate>202201</enddate><creator>Yu, Yinglan</creator><creator>Xing, LiYun</creator><creator>Li, Lian</creator><creator>Wu, Jiawei</creator><creator>He, Jinhan</creator><creator>Huang, Yuan</creator><general>Elsevier B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202201</creationdate><title>Coordination of rigidity modulation and targeting ligand modification on orally-delivered nanoparticles for the treatment of liver fibrosis</title><author>Yu, Yinglan ; Xing, LiYun ; Li, Lian ; Wu, Jiawei ; He, Jinhan ; Huang, Yuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-83a49d2c910c6e940d6ac14112cb80591d93f57728cdbd90495dc71c6d1786223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Epithelial barrier</topic><topic>FcBP modification</topic><topic>Liver fibrosis</topic><topic>Mucus barrier</topic><topic>Oral absorption</topic><topic>Rigidity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Yinglan</creatorcontrib><creatorcontrib>Xing, LiYun</creatorcontrib><creatorcontrib>Li, Lian</creatorcontrib><creatorcontrib>Wu, Jiawei</creatorcontrib><creatorcontrib>He, Jinhan</creatorcontrib><creatorcontrib>Huang, Yuan</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of controlled release</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Yinglan</au><au>Xing, LiYun</au><au>Li, Lian</au><au>Wu, Jiawei</au><au>He, Jinhan</au><au>Huang, Yuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Coordination of rigidity modulation and targeting ligand modification on orally-delivered nanoparticles for the treatment of liver fibrosis</atitle><jtitle>Journal of controlled release</jtitle><addtitle>J Control Release</addtitle><date>2022-01</date><risdate>2022</risdate><volume>341</volume><spage>215</spage><epage>226</epage><pages>215-226</pages><issn>0168-3659</issn><eissn>1873-4995</eissn><abstract>Although the individual role of ligand modification or rigidity modulation on oral administration of nanoparticle (NP) has been investigated, how they mutually affect each other remains to be elucidated. Here, we fabricated different rigidity NP with or without surface decoration of FcBP, a neonatal Fc receptor domain-binding peptide. In vitro studies showed that, without FcBP modification, stiff NP had higher transcytosis efficiency across the epithelium than softer NP, due to the different endocytosis mechanisms, intracellular trafficking routes, and exocytosis rate. Notably, after FcBP modification, such difference was narrowed, in a manner that was more favorable for softer NP to “catch up” with stiff NP, suggesting ligand modification was more conducive to exert transcytosis-promoting efficacy on softer NP. In vivo experiments demonstrated that, for ligand-free NP, high rigidity was required for efficient oral absorption and liver distribution. Further FcBP modification decreased that “rigidity threshold”, and expanded the feasible rigidity range from stiff NP to softer NP. Upon oral administration, FcBP-modified dexamethasone-loaded softer NP achieved a therapeutic efficacy comparable with stiff NP on alleviating liver fibrosis. Collectively, our study highlighted the necessity of coordinating ligand modification and rigidity modulation for oral drug delivery. We fabricated different rigidity NP with or without surface decoration of FcBP, a neonatal Fc receptor domain-binding peptide. Our results revealed that ligand-free NP, high rigidity was required for efficient oral absorption. Further FcBP modification decreased that “rigidity threshold”, and expanded the feasible rigidity range from stiff NP to softer NP. [Display omitted] •Ligand endowed nanocarriers with the ability of active-targeting.•The rigidity of ligand-modified NP would regulate receptor-mediated transcytosis.•Ligand broadened the range of feasible rigidity.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>34822908</pmid><doi>10.1016/j.jconrel.2021.11.026</doi><tpages>12</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0168-3659
ispartof Journal of controlled release, 2022-01, Vol.341, p.215-226
issn 0168-3659
1873-4995
language eng
recordid cdi_proquest_miscellaneous_2604016576
source Access via ScienceDirect (Elsevier)
subjects Epithelial barrier
FcBP modification
Liver fibrosis
Mucus barrier
Oral absorption
Rigidity
title Coordination of rigidity modulation and targeting ligand modification on orally-delivered nanoparticles for the treatment of liver fibrosis
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T08%3A36%3A54IST&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=Coordination%20of%20rigidity%20modulation%20and%20targeting%20ligand%20modification%20on%20orally-delivered%20nanoparticles%20for%20the%20treatment%20of%20liver%20fibrosis&rft.jtitle=Journal%20of%20controlled%20release&rft.au=Yu,%20Yinglan&rft.date=2022-01&rft.volume=341&rft.spage=215&rft.epage=226&rft.pages=215-226&rft.issn=0168-3659&rft.eissn=1873-4995&rft_id=info:doi/10.1016/j.jconrel.2021.11.026&rft_dat=%3Cproquest_cross%3E2604016576%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=2604016576&rft_id=info:pmid/34822908&rft_els_id=S0168365921006210&rfr_iscdi=true