Evidence map›Paper›PMID 34282781›Full record

ArticleCancers2021

ADAM9-Responsive Mesoporous Silica Nanoparticles for Targeted Drug Delivery in Pancreatic Cancer.

Etienne J Slapak, Lily Kong, Mouad El Mandili, Rienk Nieuwland, Alexander Kros, Maarten F Bijlsma, C Arnold Spek

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.0field-weighted citation impact, top 27% of its field
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

12 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
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  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Advances and Prospects in the Treatment of Pancreatic Cancer.International journal of nanomedicine · 2023
    Review
  10. Article
  11. Review
  12. 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

7 authors at 3 institutions in 2 countries.

Etienne J SlapakCenter of Experimental and Molecular Medicine, University of Amsterdam and Cancer Center Amsterdam, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0002-3228-3442
Lily KongTongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.
Mouad El MandiliCenter of Experimental and Molecular Medicine, University of Amsterdam and Cancer Center Amsterdam, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands.
Rienk NieuwlandLaboratory of Experimental Clinical Chemistry, Department of Clinical Chemistry, Amsterdam UMC, Location AMC, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0002-5671-3400
Alexander KrosTongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, China.ORCID 0000-0002-3983-3048
Maarten F BijlsmaLaboratory for Experimental Oncology and Radiobiology, University of Amsterdam and Cancer Center Amsterdam, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0001-6627-3229
C Arnold SpekCenter of Experimental and Molecular Medicine, University of Amsterdam and Cancer Center Amsterdam, Amsterdam UMC, 1105 AZ Amsterdam, The Netherlands.ORCID 0000-0002-2149-4068
Amsterdam University Medical Centers · NLHuazhong University of Science and Technology · CNOncode Institute · NL

Funding

KWF Kankerbestrijding UVA 2017-11174
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate of all cancers. This poor prognosis results from the lack of efficient systemic treatment regimens, demanding high-dose chemotherapy that causes severe side effects. To overcome dose-dependent toxicities, we explored the efficacy of targeted drug delivery using a protease-dependent drug-release system. To this end, we developed a PDAC-specific drug delivery system based on mesoporous silica nanoparticles (MSN) functionalized with an avidin-biotin gatekeeper system containing a protease linker that is specifically cleaved by tumor cells. Bioinformatic analysis identified ADAM9 as a PDAC-enriched protease, and PDAC cell-derived conditioned medium efficiently cleaved protease linkers containing ADAM9 substrates. Cleavage was PDAC specific as conditioned medium from leukocytes was unable to cleave the ADAM9 substrate. Protease linker-functionalized MSNs were efficiently capped with avidin, and cap removal was confirmed to occur in the presence of PDAC cell-derived ADAM9. Subsequent treatment of PDAC cells in vitro with paclitaxel-loaded MSNs indeed showed high cytotoxicity, whereas no cell death was observed in white blood cell-derived cell lines, confirming efficacy of the nanoparticle-mediated drug delivery system. Taken together, this research introduces a novel ADAM9-responsive, protease-dependent, drug delivery system for PDAC as a promising tool to reduce the cytotoxicity of systemic chemotherapy.

Indexed as

ADAM9drug deliverymesoporous silica nanoparticlesMSNpancreatic cancerPDAC

Identifiers

PMID34282781
PMCPMC8268056
OpenAlexW3180580933

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.