Evidence map›Paper›PMID 38321470›Full record

ArticleCell & bioscience2024

Co-Packaged PARP inhibitor and photosensitizer for targeted photo-chemotherapy of 3D ovarian cancer spheroids.

Aaron Sorrin, Anika Dasgupta, Kathryn McNaughton, Carla Arnau Del Valle, Keri Zhou, Cindy Liu, Dana M Roque, Huang Chiao Huang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell & bioscience, 2024. 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. 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

8 authors.

Aaron SorrinFischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
Anika Dasgupta *Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
Kathryn McNaughton *Fischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
Carla Arnau Del ValleFischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
Keri ZhouFischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
Cindy LiuFischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA.
Dana M RoqueDepartment of Obstetrics, Gynecology, and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Huang Chiao HuangFischell Department of Bioengineering, University of Maryland, College Park, MD, 20742, USA. hchuang@umd.edu.ORCID http://orcid.org/0000-0002-5406-0733

Funding

Addressing Chemoresistance in Pancreatic and Ovarian Cancers: Photodynamic Priming and Repurposing of Tetracyclines using Targeted Photo-Activable Multi-Inhibitor LiposomeR01CA260340 · NCI · UNIV OF MARYLAND, COLLEGE PARK · PI HUANG, HUANG CHIAO · 2021 to 2025
$3.2M
Targeting Fluid Stress-induced Chemoresistance in a 3D Carcinomatosis Perfusion Model Using Mechanism-based Photo-immunoconjugate NanoparticlesR01CA256710 · NCI · UNIV OF MARYLAND, COLLEGE PARK · PI Huang Chiao Huang, Imran Rizvi · 2023 to 2026
$2.2M
NIH HHS R01CA256710NIH HHS R01CA260340
6 · The paper itself

Abstract

backgroundWithin the last decade, poly(ADP-ribose) polymerase inhibitors (PARPi) have emerged in the clinic as an effective treatment for numerous malignancies. Preclinical data have demonstrated powerful combination effects of PARPi paired with photodynamic therapy (PDT), which involves light-activation of specialized dyes (photosensitizers) to stimulate cancer cell death through reactive oxygen species generation.

resultsIn this report, the most potent clinical PARP inhibitor, talazoparib, is loaded into the core of a polymeric nanoparticle (NP-Tal), which is interfaced with antibody-photosensitizer conjugates (photoimmunoconjugates, PICs) to form PIC-NP-Tal. In parallel, a new 3D fluorescent coculture model is developed using the parental OVCAR-8-DsRed2 and the chemo-resistant subline, NCI/ADR-RES-EGFP. This model enables quantification of trends in the evolutionary dynamics of acquired chemoresistance in response to various treatment regimes. Results reveal that at a low dosage (0.01 μM), NP-Tal kills the parental cells while sparing the chemo-resistant subline, thereby driving chemoresistance. Next, PIC-NP-Tal and relevant controls are evaluated in the 3D coculture model at multiple irradiation doses to characterize effects on total spheroid ablation and relative changes in parental and subline cell population dynamics. Total spheroid ablation data shows potent combination effects when PIC and NP-Tal are co-administered, but decreased efficacy with the conjugated formulation (PIC-NP-Tal). Analysis of cell population dynamics reveals that PIC, BPD + NP-Tal, PIC + NP-Tal, and PIC-NP-Tal demonstrate selection pressures towards chemoresistance.

conclusionsThis study provides key insights into manufacturing parameters for PARPi-loaded nanoparticles, as well as the potential role of PDT-based combination therapies in the context of acquired drug resistance.

Indexed as

3D spheroidCancer organoidOvarian cancerPARP inhibitorPhotodynamic therapyPhotoimmunotherapyPolymeric nanoparticles

Identifiers

PMID38321470
PMCPMC10845736

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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.