{"id":13196,"date":"2024-07-16T15:38:28","date_gmt":"2024-07-16T13:38:28","guid":{"rendered":"https:\/\/www.cinam.univ-mrs.fr\/cinam\/?p=13196"},"modified":"2024-07-16T15:38:28","modified_gmt":"2024-07-16T13:38:28","slug":"nanosystemes-de-dendrimeres-auto-assembles-pour-limagerie-par-resonance-magnetique-au-fluor-specifique-et-le-traitement-theranostique-efficace-des-tumeurs","status":"publish","type":"post","link":"https:\/\/www.cinam.univ-mrs.fr\/cinam\/2024\/07\/16\/nanosystemes-de-dendrimeres-auto-assembles-pour-limagerie-par-resonance-magnetique-au-fluor-specifique-et-le-traitement-theranostique-efficace-des-tumeurs\/","title":{"rendered":"Nanosyst\u00e8mes de dendrim\u00e8res auto-assembl\u00e9s pour l’imagerie par r\u00e9sonance magn\u00e9tique au fluor sp\u00e9cifique et le traitement th\u00e9ranostique efficace des tumeurs"},"content":{"rendered":"

Proc. Natl. Acad. Sci. U.S.A. <\/em>2024<\/strong>, 121<\/em>, e2322403121. DOI: 10.1073\/pnas.2322403121.<\/p>\n

Zhenbin LYU1,2,#<\/sup>, Brigino RALAHY1,#<\/sup>, Teodora-Adriana PERLES-BARBACARU3,#<\/sup>, Ling DING1,3,#<\/sup>, Yifan JIANG1<\/sup>, Baoping LIAN4<\/sup>, Tom ROUSSEL1<\/sup>, Xi LIU1,5<\/sup>, Christina GALANAKOU1<\/sup>, Erik LAURINI6<\/sup>, Aura TINTARU2<\/sup>, Suzanne GIORGIO1<\/sup>, Sabrina PRICL6,7<\/sup>, Xiaoxuan LIU4<\/sup>, Monique BERNARD3<\/sup>, Juan IOVANNA5<\/sup>, Ang\u00e8le VIOLA3<\/sup>, Ling PENG1<\/sup><\/p>\n

L\u2019imagerie par r\u00e9sonance magn\u00e9tique du fluor (IRM-19<\/sup>F) est particuli\u00e8rement prometteuse dans le domaine biom\u00e9dical en raison de l\u2019absence de fluor endog\u00e8ne dans la plupart des tissus biologiques. Mais, les applications de l\u2019IRM-19<\/sup>F ont \u00e9t\u00e9 limit\u00e9es jusqu\u2019\u00e0 pr\u00e9sent en raison du manque d\u2019agents d\u2019imagerie ayant une teneur \u00e9lev\u00e9e en fluor et des propri\u00e9t\u00e9s de relaxation ad\u00e9quates pour l\u2019IRM-19<\/sup>F, tout en \u00e9tant non toxiques et solubles dans l\u2019eau.<\/p>\n

L\u2019\u00e9quipe de Ling Peng de laboratoire Centre Interdisciplinaire de Nanoscience Marseille (CINaM) a d\u00e9velopp\u00e9 des agents d\u2019imagerie innovants constitu\u00e9s de nanomicelles supramol\u00e9culaires auto-assembl\u00e9s (1c<\/strong>@) form\u00e9es \u00e0 partir d\u2019un dendrim\u00e8re amphiphile fluor\u00e9 1c<\/strong> (Figure 1). L\u2019incorporation de groupements charg\u00e9s n\u00e9gativement aux extr\u00e9mit\u00e9s des dendrim\u00e8res, adjacents aux groupements fluor\u00e9s, emp\u00eache l\u2019agr\u00e9gation intra et intermol\u00e9culaire par r\u00e9pulsion \u00e9lectrostatique et autorise en m\u00eame temps une teneur \u00e9lev\u00e9e en fluor, favorisant la mobilit\u00e9 des groupements fluor\u00e9s ainsi que la solubilit\u00e9 des dendrim\u00e8res en milieu aqueux qui pr\u00e9sentent des temps de relaxation favorables \u00e0 l\u2019IRM-19<\/sup>F (Figure 2). Un agent d\u2019imagerie (DiR) pour la fluorescence proche infra-rouge (NIRF) ainsi qu\u2019un agent anticanc\u00e9reux, le paclitaxel (PTX), ont \u00e9t\u00e9 encapsul\u00e9s dans ces nanomicelles, permettant la d\u00e9tection des tumeurs par deux modalit\u00e9s d\u2019imagerie, en vue d\u2019une application th\u00e9ranostique dans un mod\u00e8le de cancer (Figure 3).<\/p>\n

En particulier, l\u2019encapsulation de DiR ou du paclitaxel par le nanosyst\u00e8me supramol\u00e9culaire n\u2019a pas alt\u00e9r\u00e9 les propri\u00e9t\u00e9s de relaxation des noyaux 19<\/sup>F situ\u00e9s \u00e0 la surface de la nanomicelle, ces agents \u00e9tant suffisamment distants des noyaux fluor pour \u00e9viter toute interf\u00e9rence.<\/p>\n

Dans cette \u00e9tude, le DiR et le paclitaxel ont \u00e9t\u00e9 utilis\u00e9s comme agents pharmaceutiques mod\u00e8les afin de d\u00e9montrer l\u2019efficacit\u00e9 de l\u2019imagerie multimodale IRM-19<\/sup>F\/NIRF et de la th\u00e9ranostique utilisant les agents dendrim\u00e8res supramol\u00e9culaires auto-assembl\u00e9s. Le dendrim\u00e8re 1c<\/strong>@ a \u00e9t\u00e9 \u00e9valu\u00e9 sur un mod\u00e8le de tumeur pancr\u00e9atique, un cancer pour lequel il n\u2019existe pas de m\u00e9thode de d\u00e9tection pr\u00e9coce ad\u00e9quate ni de traitement efficace. Les \u00e9tudes par IRM-19<\/sup>F r\u00e9alis\u00e9es au Centre de R\u00e9sonance Magn\u00e9tique Biologique et M\u00e9dicale (CRMBM) et par imagerie NIRF chez les souris x\u00e9nogreff\u00e9es ont confirm\u00e9 la capacit\u00e9 des deux modalit\u00e9s \u00e0 imager sp\u00e9cifiquement les tumeurs et d\u00e9montr\u00e9 l\u2019efficacit\u00e9 de l\u2018agent th\u00e9ranostique pour le traitement des tumeurs, qui s\u2019est r\u00e9v\u00e9l\u00e9 plus performant que le paclitaxel seul (Figure 3).<\/p>\n

Ces nanonyst\u00e8mes \u00e0 base de dendrim\u00e8res sont des agents prometteurs pour une prise en charge th\u00e9ranostique permettant la d\u00e9tection et le traitement simultan\u00e9s de tumeurs.\u00a0 Cette \u00e9tude montre aussi qu\u2019il serait possible, en exploitant la chimie des dendrim\u00e8res supramol\u00e9culaires auto-assembl\u00e9s, de d\u00e9velopper rapidement un large \u00e9ventail d\u2018agents th\u00e9ranostiques bas\u00e9s sur l\u2019IRM-19<\/sup>F qui pourraient \u00eatre utilis\u00e9s dans de futures applications en m\u00e9decine personnalis\u00e9e.<\/p>\n

Fig. 1 <\/strong>Schematic illustration of self-assembling supramolecular dendrimer nanosystems for fluorine magnetic resonance imaging (19<\/sup>F-MRI), 19<\/sup>F-MRI-based multimodal imaging and theranostics. (A) Self-assembly of a fluorinated amphiphilic dendrimer into nanomicelles in the absence and\/or presence of the NIRF probe DiR and the anticancer drug paclitaxel (PTX) within the supramolecular dendrimer core for 19<\/sup>F-MRI, bimodal 19<\/sup>F-MRI and NIRF imaging as well as 19<\/sup>F-MRI-based theranostics for cancer detection and treatment. (B) Chemical structures of the amphiphilic dendrimer 1c <\/strong>designed and studied for 19<\/sup>F-MRI.<\/p>\n

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Fig. 2<\/strong> Self-assembling of the amphiphilic dendrimer 1c<\/strong> into nanomicelles 1c<\/strong>@ for use as an imaging agent for fluorine magnetic resonance imaging (19<\/sup>F-MRI). (A) Dynamic light scattering results and (B) transmission electron microscopy image of the self-assembled 1c<\/strong>@ nanomicelles. (C) 19<\/sup>F-NMR spectrum of 1c<\/strong>@ in D2<\/sub>O. (D) 19<\/sup>F magnetic resonance relaxation time constants (T1<\/sub> and T2<\/sub>) for 1c<\/strong>@ at a magnetic field strength of 7 T and 20\u00b0C. (E) In vitro<\/em> 19<\/sup>F-MR images of 1c<\/strong>@ at four different concentrations. (F, G) In vivo <\/em>1<\/sup>H-MR anatomical images (top), 19<\/sup>F-MR images (middle), and overlay of 1<\/sup>H-MR and 19<\/sup>F-MR images (bottom) of tumors in pancreatic cancer xenograft mice 24 h after intravenous injection of 1c<\/strong>@ at 1c <\/strong>concentrations of (F) 0.208 mmol\/kg and (G) 0.104 mmol\/kg (corresponding to fluorine concentrations of 5.00 and 2.50 mmol\/kg, respectively). MR images were acquired in the sagittal plane with respect to the mouse.<\/p>\n

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Fig. 3 <\/strong>The anticancer drug paclitaxel (PTX) and the near-infrared fluorescence (NIRF) dye DiR encapsulated within 1c<\/strong>@ for 19<\/sup>F-MRI-based multimodal imaging and theranostic treatment of tumor in pancreatic cancer xenograft mice. (A) Transmission electron microscopy image of PTX\/DiR\/1c<\/strong>@. (B) Normalized fluorescence emission spectrum of PTX\/DiR\/1c<\/strong>@. (C) In vitro<\/em> 19<\/sup>F-MR images of PTX\/DiR\/1c<\/strong>@. (D) In vivo<\/em> NIRF imaging of pancreatic cancer xenograft mice 48 h after injection of PTX\/DiR\/1c<\/strong>@. (E) 19<\/sup>F-MRI superimposed on anatomic 1<\/sup>H-MRI of tumors in pancreatic cancer xenograft mice 48 h after accomplished treatment with of PTX\/DiR\/1c<\/strong>@. MR images were acquired in the sagittal plane with respect to the mouse. (F, G) Tumor growth inhibition in tumor-xenograft mice following intravenous injection of (F) PTX\/DiR\/1c<\/strong>@ at a PTX concentration of 7.5 mg\/kg or (G) PTX\/1c<\/strong>@ at a PTX concentration of 3.0 mg\/kg twice per week for 2 weeks. Statistical differences were assessed using two-way ANOVA with Tukey\u2019s multiple comparison test.<\/p>\n

\"\"<\/p>\n","protected":false},"excerpt":{"rendered":"

Un nouvel article dans le D\u00e9partement IMMF<\/p>\n","protected":false},"author":16,"featured_media":13199,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[2],"tags":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/www.cinam.univ-mrs.fr\/cinam\/wp-json\/wp\/v2\/posts\/13196"}],"collection":[{"href":"https:\/\/www.cinam.univ-mrs.fr\/cinam\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.cinam.univ-mrs.fr\/cinam\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.cinam.univ-mrs.fr\/cinam\/wp-json\/wp\/v2\/users\/16"}],"replies":[{"embeddable":true,"href":"https:\/\/www.cinam.univ-mrs.fr\/cinam\/wp-json\/wp\/v2\/comments?post=13196"}],"version-history":[{"count":4,"href":"https:\/\/www.cinam.univ-mrs.fr\/cinam\/wp-json\/wp\/v2\/posts\/13196\/revisions"}],"predecessor-version":[{"id":13211,"href":"https:\/\/www.cinam.univ-mrs.fr\/cinam\/wp-json\/wp\/v2\/posts\/13196\/revisions\/13211"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.cinam.univ-mrs.fr\/cinam\/wp-json\/wp\/v2\/media\/13199"}],"wp:attachment":[{"href":"https:\/\/www.cinam.univ-mrs.fr\/cinam\/wp-json\/wp\/v2\/media?parent=13196"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.cinam.univ-mrs.fr\/cinam\/wp-json\/wp\/v2\/categories?post=13196"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.cinam.univ-mrs.fr\/cinam\/wp-json\/wp\/v2\/tags?post=13196"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}