Evidence map›Paper›PMID 27106816›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2016

Urokinase-controlled tumor penetrating peptide.

Gary B Braun, Kazuki N Sugahara, Olivia M Yu, Venkata Ramana Kotamraju, Tarmo Mölder, Andrew M Lowy, Erkki Ruoslahti, Tambet Teesalu

Abstract read
In one paragraph

Article in Journal of controlled release : official journal of the Controlled Release Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

25 citing papers in PubMed, 57 citations in OpenAlex.

  1. How Key in vivo Models Can Advance Anticancer Nanotherapeutics.International journal of nanomedicine · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Exosomal targeting and its potential clinical application.Drug delivery and translational research · 2022
    Review
  7. Molecular ZIP codes in targeted drug delivery.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Review
  8. Review
  9. Review
  10. Review
  11. Isolation of Primary Hepatocytes for Testing Tumor Penetrating Peptides.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  12. Article
  13. Review
  14. Article
  15. Conventional Nanosized Drug Delivery Systems for Cancer Applications.Advances in experimental medicine and biology · 2021
    Article
  16. Homing Peptides for Cancer Therapy.Advances in experimental medicine and biology · 2021
    Review
  17. Review
  18. Article
  19. Review
  20. 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 6 institutions in 2 countries.

Gary B BraunSanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, La Jolla, CA, USA.
Kazuki N SugaharaSanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, La Jolla, CA, USA; Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Olivia M YuSanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, La Jolla, CA, USA; Biomedical Sciences Graduate Program, Department of Pharmacology, University of California San Diego, La Jolla, USA.
Venkata Ramana KotamrajuSanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, La Jolla, CA, USA.
Tarmo MölderLaboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
Andrew M LowyDepartment of Surgery, Division of Surgical Oncology, Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
Erkki RuoslahtiSanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, La Jolla, CA, USA; Center for Nanomedicine, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA.
Tambet TeesaluSanford Burnham Prebys Medical Discovery Institute, Cancer Research Center, La Jolla, CA, USA; Center for Nanomedicine, Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA, USA; Laboratory of Cancer Biology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia. Electronic address: tambet.teesalu@ut.ee.
Discovery Institute · USSanford Burnham Prebys Medical Discovery Institute · USColumbia University · USUniversity of California, San Diego · USUniversity of California, Santa Barbara · USUniversity of Tartu · EE

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael Jackson · 1985 to 2026
$107.2M
A nanosystem for tumor treatment and imagingR01CA188883 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI RUOSLAHTI, ERKKI · 2014 to 2018
$2.0M
The role of fibroblasts in the activities of tissue penetrating peptidesR01CA167174 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI SUGAHARA, KAZUKI · 2012 to 2016
$1.9M
Trans-disciplinary Postdoctoral Training in Cancer BiologyT32CA121949 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI RONAI, ZEEV A. · 2007 to 2011
$1.8M
NCI NIH HHS P30 CA030199NCI NIH HHS R01 CA167174NCI NIH HHS R01 CA188883NCI NIH HHS T32 CA121949Wellcome TrustWellcome Trust WT095077MA
6 · The paper itself

Abstract

Tumor penetrating peptides contain a cryptic (R/K)XX(R/K) CendR element that must be C-terminally exposed to trigger neuropilin-1 (NRP-1) binding, cellular internalization and malignant tissue penetration. The specific proteases that are involved in processing of tumor penetrating peptides identified using phage display are not known. Here we design de novo a tumor-penetrating peptide based on consensus cleavage motif of urokinase-type plasminogen activator (uPA). We expressed the peptide, uCendR (RPARSGR↓SAGGSVA, ↓ shows cleavage site), on phage or coated it onto silver nanoparticles and showed that it is cleaved by uPA, and that the cleavage triggers binding to recombinant NRP-1 and to NPR-1-expressing cells. Upon systemic administration to mice bearing uPA-overexpressing breast tumors, FAM-labeled uCendR peptide and uCendR-coated nanoparticles preferentially accumulated in tumor tissue. We also show that uCendR phage internalization into cultured cancer cells and its penetration in explants of murine tumors and clinical tumor explants can be potentiated by combining the uCendR peptide with tumor-homing module, CRGDC. Our work demonstrates the feasibility of designing tumor-penetrating peptides that are activated by a specific tumor protease. As upregulation of protease expression is one of the hallmarks of cancer, and numerous tumor proteases have substrate specificities compatible with proteolytic unmasking of cryptic CendR motifs, the strategy described here may provide a generic approach for designing proteolytically-actuated peptides for tumor-penetrative payload delivery.

Indexed as

AnimalsBacteriophage T7Cell Line, TumorDrug CarriersHumansMammary Neoplasms, AnimalMetal NanoparticlesMice, Inbred BALB CPeptidesSilverUrokinase-Type Plasminogen ActivatorDrug CarriersPeptidesSilverUrokinase-Type Plasminogen ActivatorC-end ruleNeuropilin-1Silver nanoparticlesTumor targetingUrokinaseα(v) integrins

Identifiers

PMID27106816
PMCPMC5359125
OpenAlexW2340338369

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.