Evidence map›Paper›PMID 28913666›Full record

ArticleJournal of pharmacokinetics and pharmacodynamics2017

Quantitative modeling of the dynamics and intracellular trafficking of far-red light-activatable prodrugs: implications in stimuli-responsive drug delivery system.

Mengjie Li, Pritam Thapa, Pallavi Rajaputra, Moses Bio, Cody J Peer, William D Figg, Youngjae You, Sukyung Woo

Open access · greenAbstract read
In one paragraph

Article in Journal of pharmacokinetics and pharmacodynamics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. PBPK modeling-based optimization of site-specific chemo-photodynamic therapy with far-red light-activatable paclitaxel prodrug.Journal of controlled release : official journal of the Controlled Release Society · 2019
    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 at 2 institutions in 1 country.

Mengjie LiDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73117, USA.
Pritam ThapaDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73117, USA.
Pallavi RajaputraDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73117, USA.
Moses BioDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73117, USA.
Cody J PeerClinical Pharmacology Program, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
William D FiggClinical Pharmacology Program, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
Youngjae YouDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73117, USA. youngjae-you@ouhsc.edu.
Sukyung WooDepartment of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73117, USA. sukyung-woo@ouhsc.edu.
University of Oklahoma Health Sciences Center · USNational Cancer Institute · US

Funding

Using Clinical Pharmacology Principles to Develop New Anticancer TherapiesZICSC006537 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI FIGG, WILLIAM DOUGLAS · 2009 to 2025
$14.4M
Site Specific Drug Delivery with Light-responsive Conjugates for Photo-biomodulationR01GM113940 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Youngjae You · 2015 to 2026
$3.0M
National Institute of General Medical Sciences R01GM113940NIGMS NIH HHS R01 GM113940U.S. Department of Defense W81XWH-09-1-0071
6 · The paper itself

Abstract

The combination of photodynamic therapy (PDT) with anti-tumor agents is a complimentary strategy to treat local cancers. We developed a unique photosensitizer (PS)-conjugated paclitaxel (PTX) prodrug in which a PS is excited by near-infrared wavelength light to site-specifically release PTX while generating singlet oxygen (SO) to effectively kill cancer cells with both PTX and SO. The aim of the present study was to identify the determinants influencing the combined efficacy of this light-activatable prodrug, especially the bystander killing effects from released PTX. Using PS-conjugated PTX as a model system, we developed a quantitative mathematical model describing the intracellular trafficking. Dynamics of the prodrug and the model predictions were verified with experimental data using human cancer cells in vitro. The sensitivity analysis suggested that parameters related to extracellular concentration of released PTX, prodrug uptake, target engagement, and target abundance are critical in determining the combined killing efficacy of the prodrug. We found that released PTX cytotoxicity was most sensitive to the retention time of the drug in extracellular space. Modulating drug internalization and conjugating the agents targeted to abundant receptors may provide a new strategy for maximizing the killing capacity of the far-red light-activatable prodrug system. These results provide guidance for the design of the PDT combination study in vivo and have implications for other stimuli-responsive drug delivery systems.

Indexed as

Antineoplastic AgentsCell Line, TumorCell SurvivalDrug Delivery SystemsHumansIntracellular FluidModels, BiologicalPaclitaxelPhotochemotherapyPhotosensitizing AgentsProdrugsProtein TransportAntineoplastic AgentsPaclitaxelPhotosensitizing AgentsProdrugsBystander killingCombination therapyIntracellular PK/PD modeling and simulationPaclitaxelPharmacodynamicsPharmacokineticsPhotodynamic therapy

Identifiers

PMID28913666
PMCPMC5688019
OpenAlexW2755665569

What OpenQuestion holds

Textmetadata
LicenceTDM
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.