Evidence map›Paper›PMID 40971053›Full record

ArticleMolecular biology reports2025

Folate- and chitosan-functionalized lipid nanoparticles for co-delivery of pioglitazone and simvastatin to enhance hepatic cancer therapy: effects on IL-1β, IL-6, BCL2/BAX gene expression, and GPX4, COX-2, and MMP-9 activities.

Riyadh F Alzahrani, Muteb S Almuqati, Sultan A AlAli, Khalid A Alamer, Sayed Rabbani, Mohammed S Alqahtani, Ahmed H Bakheit, Hanadi H Asiri, Gamaleldin I Harisa

Abstract read
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Article in Molecular biology reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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

9 authors.

Riyadh F AlzahraniDepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
Muteb S AlmuqatiDepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
Sultan A AlAliDepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
Khalid A AlamerDepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
Sayed RabbaniDepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
Mohammed S AlqahtaniDepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
Ahmed H BakheitDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
Hanadi H AsiriDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
Gamaleldin I HarisaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia. harisa@ksu.edu.sa.

Funding

King Saud University ROF-2025-1037
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) is a leading cause of cancer mortality, largely due to multidrug resistance (MDR). Pioglitazone (PIO) and simvastatin (STAT), originally used for metabolic disorders, also modulate oncogenic pathways. This study evaluated a nanotechnology-based co-delivery approach to improve their therapeutic efficacy against chemoresistant HCC. METHODS AND

resultsLipid nanoparticles (LNPs) encapsulating PIO and STAT (PSLNPs) were fabricated and functionalized with chitosan (CPSLNPs) or folate-conjugated chitosan (FCPSLNPs). Physicochemical properties (size, zeta potential, polydispersity) were characterized. Hemolysis and MTT assays assessed safety and cytotoxicity in HepG2 cells. qPCR quantified IL-1β, IL-6, BCL2, and BAX expression. Molecular docking examined drug interactions with key proteins involved in proliferation, ferroptosis, inflammation, and MDR. All formulations exhibited nanoscale size and uniform dispersion. Chitosan modification increased zeta potential, and stability studies confirmed consistent physicochemical properties. Hemolysis assays demonstrated biocompatibility. Compared with free drugs, PSLNPs and their functionalized forms significantly enhanced cytotoxicity in HepG2 cells. Gene expression analysis showed downregulation of IL-1β, IL-6, and BCL2, with upregulation of BAX, indicating enhanced apoptosis. Docking studies revealed STAT strongly interacted with SDH, GST, HDAC1, and JNK3, while PIO showed higher affinity for COX-2, GPX4, HO-1, and MMP-9, supporting complementary multi-target effects.

conclusionFunctionalized PSLNPs improved the delivery and efficacy of PIO and STAT, overcoming MDR by modulating multiple oncogenic pathways. These results highlight their promise as a multi-targeted nanotherapeutic strategy for HCC treatment.

Indexed as

Liver NeoplasmsPioglitazoneSimvastatinbcl-2-Associated X ProteinCarcinoma, HepatocellularChitosanCyclooxygenase 2Drug Delivery SystemsFolic AcidGene Expression Regulation, NeoplasticHep G2 CellsHumansInterleukin-1betaInterleukin-6LipidsLiposomesBAX protein, humanbcl-2-Associated X ProteinBCL2 protein, humanChitosanCyclooxygenase 2Folic AcidIL1B protein, humanIL6 protein, humanInterleukin-1betaInterleukin-6Lipid NanoparticlesLipidsLiposomesMatrix Metalloproteinase 9MMP9 protein, humanPioglitazoneProto-Oncogene Proteins c-bcl-2PTGS2 protein, humanSimvastatinChemoresistant cancerDrug repurposingFerroptosisFolate-modified chitosanGene expressionMolecular dockingTargeted nanotherapy

Identifiers

PMID40971053

What Socratic holds

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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 Socratic graph.