Evidence map›Paper›PMID 41097779›Full record

ArticleCancers2025

Liver-Specific Nanoparticle-Mediated Delivery and MMP-Triggered Release of Veratridine to Effectively Target Metastatic Colorectal Cancer.

Mahadi Hasan, Morgan Eikanger, Sanam Sane, Krishantha S K Wijewardhane, John L Slunecka, Jessica Freeling, Khosrow Rezvani, Grigoriy Sereda

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Mahadi HasanDepartment of Chemistry, University of South Dakota, 414 E Clark Street, Vermillion, SD 57069, USA.ORCID 0009-0006-8767-0905
Morgan EikangerDivision of Biomedical and Translational Sciences, Sanford School of Medicine, University of South Dakota, 414 E Clark Street, Vermillion, SD 57069, USA.ORCID 0000-0002-6435-6175
Sanam SaneDivision of Biomedical and Translational Sciences, Sanford School of Medicine, University of South Dakota, 414 E Clark Street, Vermillion, SD 57069, USA.
Krishantha S K WijewardhaneDepartment of Chemistry, University of South Dakota, 414 E Clark Street, Vermillion, SD 57069, USA.
John L SluneckaDivision of Biomedical and Translational Sciences, Sanford School of Medicine, University of South Dakota, 414 E Clark Street, Vermillion, SD 57069, USA.
Jessica FreelingDivision of Biomedical and Translational Sciences, Sanford School of Medicine, University of South Dakota, 414 E Clark Street, Vermillion, SD 57069, USA.
Khosrow RezvaniDivision of Biomedical and Translational Sciences, Sanford School of Medicine, University of South Dakota, 414 E Clark Street, Vermillion, SD 57069, USA.
Grigoriy SeredaDepartment of Chemistry, University of South Dakota, 414 E Clark Street, Vermillion, SD 57069, USA.

Funding

National Cancer Institute of the National Institutes of Health 1R03 CA223935-01 and 1R03CA 290549-01
6 · The paper itself

Abstract

backgroundDespite considerable advances to improve colorectal cancer (CRC) survival over the last decade, therapeutic challenges remain due to the rapid metastatic dissemination of primary tumors. This study revealed the apoptotic and anti-growth mechanism of VTD, a previously used anti-hypertensive supplement, can elevate UBXN2A, a known tumor suppressor protein in CRC, and simultaneously enhance intrinsic and extrinsic apoptosis in metastatic cancer cells. METHODS AND

resultsAn AOM/DSS mouse model of CRC showed that UBXN2A haplosufficient (UBXN2A +/-) mice treated with VTD had less tumor burden than mice with the full UBXN2A gene treated with vehicle. We have previously shown that casein-coated mesoporous silica nanoparticles (MSNs) offer an effective local delivery of drugs at tumor sites. Our findings demonstrate that the high rate of extracellular release of matrix metalloproteinases (MMPs), particularly MMP-7, by metastatic colon cancer cells, triggers the release of VTD from casein-coated mesoporous MSNs. This shows the "Zip Code" mechanism for the local enrichment of VTD at the tumor sites. After in vitro drug release verification, two independent mouse experiments, a xenograft and a splenolepatic metastatic mouse model of CRC, were used to evaluate the therapeutic efficacy of VTD-loaded and casein-coated carboxylated mesoporous silica nanoparticles, MSN-COOH/VTD/CAS (VTD, 0.2 mg/kg). Animal experiments revealed that MSN-COOH/VTD/CAS (VTD, 0.2 mg/kg) slows down the progress of tumors. Mass spectrometry (MS) revealed improved pharmacokinetics (PK) profile as MSN-COOH/VTD/CAS had less VTD accumulation in non-cancerous organs compared to pure VTD. We further improved nanoparticle targeting and drug release by shifting to calcium-based particles (CBPs). The engineered CBPs demonstrated higher drug-releasing performance. Without the MMPs trigger, MSNs show slow and continuous "drug leak" over longer period of time whereas CCSMPs stops leakage within an hour. Additionally, CBPs showed higher sensitivity to MMP-7 than MMP-9, enhancing the targetability of CBPs for CRC metastatic tumors with excessive extracellular MMP-7.

conclusionsThis study introduces a new platform utilizing nanoparticle-based site-specific delivery of a plant-based anti-metastatic molecule, veratridine, with enhanced safety and therapeutic efficacy for the treatment of metastatic CRC.

Indexed as

colorectal cancerMMPsnanoparticlestargeted drug deliveryveratridine

Identifiers

PMID41097779
PMCPMC12524202

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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.