Evidence map›Paper›PMID 34522092›Full record

ArticleNanotechnology, science and applications2021

Pharmacodynamic Studies of Fluorescent Diamond Carriers of Doxorubicin in Liver Cancer Cells and Colorectal Cancer Organoids.

Ron Firestein, Cezary Marcinkiewicz, Linyan Nie, Hui Kheng Chua, Ines Velazquez Quesada, Marco Torelli, Mark Sternberg, Bojana Gligorijevic, Olga Shenderova, Romana Schirhagl and 1 more

Abstract read
In one paragraph

Article in Nanotechnology, science and applications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
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

11 authors.

Ron Firestein *Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, 3168, Australia.
Cezary Marcinkiewicz *Debina Diagnostics Inc., Newtown Square, PA, USA.
Linyan NieGroningen University, Groningen, 9727, the Netherlands.
Hui Kheng ChuaCentre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, 3168, Australia.ORCID 0000-0002-6047-4027
Ines Velazquez QuesadaCollege of Engineering, Department of Bioengineering, Temple University, Philadelphia, PA, USA.
Marco TorelliAdámas Nanotechnologies, Inc., Raleigh, NC, 27617, USA.
Mark SternbergDebina Diagnostics Inc., Newtown Square, PA, USA.
Bojana GligorijevicCollege of Engineering, Department of Bioengineering, Temple University, Philadelphia, PA, USA.
Olga ShenderovaAdámas Nanotechnologies, Inc., Raleigh, NC, 27617, USA.
Romana SchirhaglGroningen University, Groningen, 9727, the Netherlands.
Giora Z FeuersteinDebina Diagnostics Inc., Newtown Square, PA, USA.

Funding

Targeting invadopodia-related mechanisms of cancer cell invasion and metastasisR01CA230777 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI GLIGORIJEVIC, BOJANA · 2019 to 2023
$1.9M
NCI NIH HHS R01 CA230777
6 · The paper itself

Abstract

backgroundWe recently reported on preferential deposition of bare fluorescent diamond particles FDP-NV-700/800nm (FDP-NV) in the liver following intravenous administration to rats. The pharmacokinetics of FDP-NV in that species indicated short residency in the circulation by rapid clearance by the liver. Retention of FDP-NV in the liver was not associated with any pathology. These observations suggested that cancer therapeutics, such as doxorubicin, linked to FDP-NV, could potentially serve for anti-cancer treatment while sparing toxicities of peripheral organs. PURPOSE: To generate proof-of-concept (POC) and detail mechanisms of action of doxorubicin-coated FDP-NV-700/800nm (FDP-DOX) as a prospective chemotherapeutic for metastatic liver cancer.

methodsFDP-DOX was generated by adsorption chemistry. Experimental design included concentration and time-dependent efficacy studies as compared with naïve (baren) FDP-NV in in vitro liver cancer cells models. Uptake of FDP-NV and FDP-DOX by HepG-2, Hep-3B and hCRC organoids were demonstrated by flow-cytometry and fluorescent microscopy. FDP-DOX pharmacodynamic effects included metabolic as well as cell death biomarkers Annexin V, TUNEL and LDH leakage. DOX desorpted from FDP-DOX was assessed by confocal microscopy and chemical assay of cells fractions.

resultsFDP-DOX efficacy was dose- and time-dependent and manifested in both liver cancer cell lines and human CRC organoids. FDP-DOX was rapidly internalized into cancer cells/organoids leading to cancer growth inhibition and apoptosis. FDP-DOX disrupted cell membrane integrity as evident by LDH release and suppressing mitochondrial metabolic pathways (AlamarBlue assay). Access of free DOX to the nuclei was confirmed by direct UV-Visible fluorescent assay and confocal microscopy of DOX fluorescence.

conclusionThe rapid uptake and profound cancer inhibition observed using FDP-DOX in clinically relevant cancer models, highlight FDP-DOX promise for cancer chemotherapeutics. We also conclude that the in vitro data justify further investment in in vivo POC studies.

Indexed as

apoptosisdoxorubicinfluorescent diamond particles-NV-700/800nmhuman colorectal cancer organoidsliver cancer cell-lines

Identifiers

PMID34522092
PMCPMC8434926

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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.