P-selectin is a nanotherapeutic delivery target in the tumor microenvironment Journal Article

Authors: Shamay, Y.; Elkabets, M.; Li, H.; Shah, J.; Brook, S.; Wang, F.; Adler, K.; Baut, E.; Scaltriti, M.; Jena, P. V.; Gardner, E. E.; Poirier, J. T.; Rudin, C. M.; Baselga, J.; Haimovitz-Friedman, A.; Heller, D. A.
Article Title: P-selectin is a nanotherapeutic delivery target in the tumor microenvironment
Abstract: Disseminated tumors are poorly accessible to nanoscale drug delivery systems because of the vascular barrier, which attenuates extravasation at the tumor site. We investigated P-selectin, a molecule expressed on activated vasculature that facilitates metastasis by arresting tumor cells at the endothelium, for its potential to target metastases by arresting nanomedicines at the tumor endothelium. We found that P-selectin is expressed on cancer cells in many human tumors. To develop a targeted drug delivery platform, we used a fucosylated polysaccharide with nanomolar affinity to P-selectin. The nanoparticles targeted the tumor microenvironment to localize chemotherapeutics and a targeted MEK (mitogen-activated protein kinase kinase) inhibitor at tumor sites in both primary and metastatic models, resulting in superior antitumor efficacy. In tumors devoid of P-selectin, we found that ionizing radiation guided the nanoparticles to the disease site by inducing P-selectin expression. Radiation concomitantly produced an abscopal-like phenomenon wherein P-selectin appeared in unirradiated tumor vasculature, suggesting a potential strategy to target disparate drug classes to almost any tumor. © 2016, American Association for the Advancement of Science. All rights reserved.
Journal Title: Science Translational Medicine
Volume: 8
Issue: 345
ISSN: 1946-6234
Publisher: American Association for the Advancement of Science  
Date Published: 2016-06-29
Start Page: 345ra87
Language: English
DOI: 10.1126/scitranslmed.aaf7374
PROVIDER: scopus
PUBMED: 27358497
PMCID: PMC5064151
Notes: Article -- Export Date: 2 August 2016 -- Source: Scopus
Citation Impact
MSK Authors
  1. Daniel Alan Heller
    73 Heller
  2. Prakrit Vaibhav Jena
    24 Jena
  3. Jose T Baselga
    481 Baselga
  4. Maurizio Scaltriti
    158 Scaltriti
  5. Feng Wang
    3 Wang
  6. Charles Rudin
    304 Rudin
  7. John Thomas Poirier
    79 Poirier
  8. Eric Edison Gardner
    14 Gardner
  9. Samuel Ian Brook
    5 Brook
  10. Janki Kalpesh Shah
    19 Shah
  11. Yosef   Shamay
    15 Shamay
  12. Hongyan   Li
    7 Li
  13. Keren   Adler
    1 Adler
  14. Emily Jean Baut
    2 Baut