ArticleJournal of controlled release : official journal of the Controlled Release Society2015
A stapled peptide antagonist of MDM2 carried by polymeric micelles sensitizes glioblastoma to temozolomide treatment through p53 activation.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 58 citations in OpenAlex.
- Development of an All-Hydrocarbon Stapled Peptide Targeting BRK1 in Triple-Negative Breast Cancer.ACS medicinal chemistry letters · 2025Article
- Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells.Metabolites · 2024Review
- Three-Dimensional Gene Regulation Network in Glioblastoma Ferroptosis.International journal of molecular sciences · 2023Article
- MDM2 Inhibition in the Treatment of Glioblastoma: From Concept to Clinical Investigation.Biomedicines · 2023Review
- Exploiting Nanomedicine for Cancer Polychemotherapy: Recent Advances and Clinical Applications.Pharmaceutics · 2023Review
- Alterations in Molecular Profiles Affecting Glioblastoma Resistance to Radiochemotherapy: Where Does the Good Go?Cancers · 2022Review
- Design of stapled peptide-based PROTACs for MDM2/MDMX atypical degradation and tumor suppression.Theranostics · 2022Article
- Design of ultrahigh-affinity and dual-specificity peptide antagonists of MDM2 and MDMX for P53 activation and tumor suppression.Acta pharmaceutica Sinica. B · 2021Article
- The role of E3 ubiquitin ligases in the development and progression of glioblastoma.Cell death and differentiation · 2021Review
- MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy.Frontiers in oncology · 2021Review
- Drug Delivery Nanosystems in Glioblastoma Multiforme Treatment: Current State of the Art.Current neuropharmacology · 2021Review
- All-stage precisional glioma targeted therapy enabled by a well-designed D-peptide.Theranostics · 2020Article
- Nanocarrier-based drug combination therapy for glioblastoma.Theranostics · 2020Review
- TRIM21 overexpression promotes tumor progression by regulating cell proliferation, cell migration and cell senescence in human glioma.American journal of cancer research · 2020Article
- A tetrameric protein scaffold as a nano-carrier of antitumor peptides for cancer therapy.Biomaterials · 2019Article
- Dithiocarbamate-inspired side chain stapling chemistry for peptide drug design.Chemical science · 2019Article
- MTBP regulates cell survival and therapeutic sensitivity in TP53 wildtype glioblastomas.Theranostics · 2019Article
- YB-1 modulates the drug resistance of glioma cells by activation of MDM2/p53 pathway.Drug design, development and therapy · 2019Article
- Efficacy of the MDM2 Inhibitor SAR405838 in Glioblastoma Is Limited by Poor Distribution Across the Blood-Brain Barrier.Molecular cancer therapeutics · 2018Article
- Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Antagonizing MDM2 and MDMX to activate the tumor suppressor protein p53 is an attractive therapeutic paradigm for the treatment of glioblastoma multiforme (GBM). However, challenges remain with respect to the poor ability of p53 activators to efficiently cross the blood-brain barrier and/or blood-brain tumor barrier and to specifically target tumor cells. To circumvent these problems, we developed a cyclic RGD peptide-conjugated poly(ethylene glycol)-co-poly(lactic acid) polymeric micelle (RGD-M) that carried a stapled peptide antagonist of both MDM2 and MDMX (sPMI). The peptide-carrying micelle RGD-M/sPMI was prepared via film-hydration method with high encapsulation efficiency and loading capacity as well as ideal size distribution. Micelle encapsulation dramatically increased the solubility of sPMI, thus alleviating its serum sequestration. In vitro studies showed that RGD-M/sPMI efficiently inhibited the proliferation of glioma cells in the presence of serum by activating the p53 signaling pathway. Further, RGD-M/sPMI exerted potent tumor growth inhibitory activity against human glioblastoma in nude mouse xenograft models. Importantly, the combination of RGD-M/sPMI and temozolomide--a standard chemotherapy drug for GBM increased antitumor efficacy against glioblastoma in experimental animals. Our results validate a combination therapy using p53 activators with temozolomide as a more effective treatment for GBM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.