Details

Autor(en) / Beteiligte

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

Titel

A Multifunctional Mesothelin Antibody-tagged Microparticle Targets Human Mesotheliomas

Ist Teil von

• The journal of histochemistry and cytochemistry, 2012-09, Vol.60 (9), p.658-674

Ort / Verlag

Los Angeles, CA: SAGE Publications

Erscheinungsjahr

2012

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.