Evidence map›Paper›PMID 41005742›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2025

Lipid nanomedicine simultaneously inhibits BRD4/PI3K and MDM2/XIAP signaling pathways for effective treatment of Medulloblastoma.

Bharti Sethi, Aditya Gupta, Qiaoyu Pan, Sohan Mahto, Ajaykumar Chittipolu, Helen Erickson, Virender Kumar, Yanfei Chen, Zhongzhi Wu, Yuxiang Dong and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Bharti SethiDepartment of Pharmaceutical Sciences, The University of Nebraska Medical Center, Omaha, NE 68198, USA.
Aditya GuptaDepartment of Pharmaceutical Sciences, The University of Nebraska Medical Center, Omaha, NE 68198, USA.
Qiaoyu PanDepartment of Pharmaceutical Sciences, The University of Nebraska Medical Center, Omaha, NE 68198, USA.
Sohan MahtoDepartment of Pharmaceutical Sciences, The University of Nebraska Medical Center, Omaha, NE 68198, USA.
Ajaykumar ChittipoluDepartment of Pharmaceutical Sciences, The University of Nebraska Medical Center, Omaha, NE 68198, USA.
Helen EricksonDepartment of Pharmaceutical Sciences, The University of Nebraska Medical Center, Omaha, NE 68198, USA.
Virender KumarDepartment of Pharmaceutical Sciences, The University of Nebraska Medical Center, Omaha, NE 68198, USA.
Yanfei ChenDepartment of Pharmaceutical Sciences, The University of Tennessee Health Science Center, Memphis 38105, USA.
Zhongzhi WuDepartment of Pharmaceutical Sciences, The University of Tennessee Health Science Center, Memphis 38105, USA.
Yuxiang DongDepartment of Pharmaceutical Sciences, The University of Nebraska Medical Center, Omaha, NE 68198, USA.
Wei LiDepartment of Pharmaceutical Sciences, The University of Tennessee Health Science Center, Memphis 38105, USA.
Donald R RonningDepartment of Pharmaceutical Sciences, The University of Nebraska Medical Center, Omaha, NE 68198, USA.
Donald W CoulterDepartment of Pediatrics, The University of Nebraska Medical Center, Omaha, NE 68198, USA.
Ram I MahatoDepartment of Pharmaceutical Sciences, The University of Nebraska Medical Center, Omaha, NE 68198, USA. Electronic address: ram.mahato@unmc.edu.

Funding

Dual inhibition of MDM2 and XIAP as a therapeutic strategy in cancerR01CA240447 · NCI · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI LI, WEI, ZHOU, MUXIANG · 2020 to 2024
$2.7M
Lipid nanomedicine targeting multiple signaling pathways of medulloblastomaR01NS128336 · NINDS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Ram I. Mahato · 2022 to 2026
$2.4M
Overcoming Resistance Mechanisms in Hedgehog and Myc-amplified MedulloblastomaR01NS116037 · NINDS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI COULTER, DONALD, MAHATO, RAM I. · 2021 to 2025
$1.9M
NCI NIH HHS R01 CA240447NINDS NIH HHS R01 NS116037NINDS NIH HHS R01 NS128336
6 · The paper itself

Abstract

Medulloblastoma (MB) is the most common childhood brain tumor arising from the cerebellum. PI3K and BRD4 signaling pathways are known to induce MB cell growth, cancer stem cell (CSC) proliferation, and tumor resistance. Further, the tumor suppressor gene TP53 is found to be inactivated in MB due to overexpression of its negative regulator MDM2. In this study, we synthesized MDP5, a potent BRD4/PI3K dual inhibitor, and JW475A, a potent dual MDM2 and XIAP inhibitor. The combination of these two drugs significantly decreased the colony formation capacity compared to individual drugs. Given the challenge of inefficient drug transport across the blood-brain barrier (BBB), we prepared rabies virus glycoprotein (RVG) peptide decorated lipid nanoparticles (LNPs), which showed 4.9 ± 0.1 and 4.8 ± 0.1 % loading for MDP5 and JW475A, respectively. In vivo studies in mice showed that Cy5.5 labeled RVG-LNPs were detected in the brain after systemic administration. Combination drug-loaded RVG-LNPs significantly decreased the MB growth in orthotopic mouse model of MB compared to free drug combination and non-targeted LNPs. This study indicates that MDP5 and JW475A -loaded RVG-LNPs are a promising drug brain delivery system worth exploring further in clinical settings for MB therapy.

Indexed as

Antineoplastic AgentsCerebellar NeoplasmsMedulloblastomaNanoparticlesPhosphoinositide-3 Kinase InhibitorsAnimalsBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorGlycoproteinsHumansLipidsMiceMice, NudeNuclear ProteinsPeptide FragmentsAntineoplastic AgentsBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsGlycoproteinsLipidsMDM2 protein, humanNuclear ProteinsPeptide FragmentsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-mdm2rabies virus glycoprotein peptideTranscription FactorsViral ProteinsBRD4JW475ALNPsMDP5MedulloblastomaPI3KRVG-peptide

Identifiers

PMID41005742
PMCPMC12688409

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.