A Multifunctional Mesothelin Antibody-tagged Microparticle Targets Human Mesotheliomas

Sherrill L. Macura, Jedd M. Hillegass, Jeremy L. Steinbacher, Maximilian B. MacPherson, Arti Shukla, Stacie L. Beuschel, Timothy N. Perkins, Kelly J. Butnor, Melissa J. Lathrop, Mutlay Sayan, Khan Hekmatyar, Douglas J. Taatjes, Risto A. Kauppinen, Christopher C. Landry, Brooke T. Mossman

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Pleural and peritoneal mesotheliomas (MMs) are chemoresistant tumors with no effective therapeutic strategies. The authors first injected multifunctional, acid-prepared mesoporous spheres (APMS), microparticles functionalized with tetraethylene glycol oligomers, intraperitoneally into rodents. Biodistribution of APMS was observed in major organs, peritoneal lavage fluid (PLF), and urine of normal mice and rats. After verification of increased mesothelin in human mesotheliomas injected into severe combined immunodeficient (SCID) mice, APMS were then functionalized with an antibody to mesothelin (APMS-MB) or bovine serum albumin (BSA), a nonspecific protein control, and tumor targeting was evaluated by inductively coupled plasma mass spectrometry and multifluorescence confocal microscopy. Some APMS were initially cleared via the urine over a 24 hr period, and small amounts were observed in liver, spleen, and kidneys at 24 hr and 6 days. Targeting with APMS-MB increased APMS uptake in mesenteric tumors at 6 days. Approximately 10% to 12% of the initially injected amount was observed in both spheroid and mesenteric MM at this time point. The data suggest that localized delivery of APMS-MB into the peritoneal cavity after encapsulation of drugs, DNA, or macromolecules is a novel therapeutic approach for MM and other tumors (ovarian and pancreatic) that overexpress mesothelin.

Original languageEnglish (US)
Pages (from-to)658-674
Number of pages17
JournalJournal of Histochemistry and Cytochemistry
Volume60
Issue number9
DOIs
StatePublished - Sep 2012

Keywords

  • amorphous silica
  • malignant mesothelioma
  • mesothelin
  • targeted microparticle

ASJC Scopus subject areas

  • Anatomy
  • Histology

Fingerprint Dive into the research topics of 'A Multifunctional Mesothelin Antibody-tagged Microparticle Targets Human Mesotheliomas'. Together they form a unique fingerprint.

Cite this