Summary of project PR002267
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002267. The data can be accessed directly via it's Project DOI: 10.21228/M8KV62 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002267 |
| Project DOI: | doi: 10.21228/M8KV62 |
| Project Title: | Lactate-coated polyurea-siRNA dendriplex: a gene therapy-directed and metabolism-based strategy to impair glioblastoma (GBM) |
| Project Summary: | Glioblastoma (GBM) is a highly lethal disease with limited treatment options due to its infiltrative nature and the lack of efficient therapy able to cross the protective blood-brain barrier (BBB). GBMs are metabolically characterized by increased glycolysis and glutamine dependence. This study explores a novel metabolism-based therapeutic approach using a polyurea generation 4 dendrimer (PUREG4) surface functionalized with lactate (LA) (PUREG4-LA12), to take advantage of glucose-dependent monocarboxylate transporters (MCTs) overexpression, loaded with selenium-chrysin (SeChry) and temozolomide (TMZ) or complexed with anti-glutaminase (GLS1) siRNAs to abrogate glutamine dependence. The anti-GLS1 siRNA dendriplex with PUREG4-LA12 (PUREG4-LA12-anti-GLS1-siRNA) knocked down GLS1 in the GBM cell lines. In two in vitro BBB models, these dendriplexes successfully crossed the BBB, decreased GLS1 expression and altered the exometabolome of GBM cell lines, concomitantly with autophagy activation. Our findings highlight the potential of targeting glucose and glutamine pathways in GBM using dendrimer-based nanocarriers, overcoming the BBB and disrupting key metabolic processes in GBM cells. |
| Institute: | ITQB NOVA |
| Last Name: | G Gonçalves |
| First Name: | Luís |
| Address: | Avenida Republica, Oeiras, 2780-157 Oeiras, Portugal |
| Email: | lgafeira@itqb.unl.pt |
| Phone: | 214469464 |
| Contributors: | Filipa Martins; Renata Arada; Hélio Barros, Paulo Matos, José Ramalho, Valentín Ceña, Vasco D.B. Bonifácio, Luís G. Gonçalves, Jacinta Serpa |
Summary of all studies in project PR002267
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003657 | Lactate-coated polyurea-siRNA dendriplex: a gene therapy-directed and metabolism-based strategy to impair glioblastoma (GBM) | Homo sapiens | ITQB NOVA | NMR | 2025-04-08 | 1 | 109 | Uploaded data (169.6M)* |
