A multifunctional mesothelin antibody-tagged microparticle targets human mesotheliomas

Our plain-English summary of A multifunctional mesothelin antibody-tagged microparticle targets human mesotheliomas, by S.L. Macura, J.M. Hillegass, J.L. Steinbacher, et al (The Journal of Histochemistry and Cytochemistry, 2012).

The study

• Authors: S.L. Macura, J.M. Hillegass, J.L. Steinbacher, M.B. MacPherson, A. Shukla, S.L. Beuschel, T.N. Perkins, K.J. Butnor, M.J. Lathrop, M. Sayan, K. Hekmatyar, D.J. Taatjes, R.A. Kauppinen, C.C. Landry, B.T. Mossman
• Journal: The Journal of Histochemistry and Cytochemistry
• Published: 2012;60(9):658-74
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This was a laboratory animal study of a possible drug-delivery particle for mesothelioma. It did not study asbestos exposure. The particles, called APMS, were amorphous silica microparticles injected into the abdominal (peritoneal) cavity. In healthy Wistar rats, particles were found in urine from 0.5 to 24 hours but not at 144 hours (6 days), and were seen in liver, spleen, kidney and bladder at 6 days. In SCID mice carrying human mesothelioma tumors grown from the PPM Mill cell line, the authors compared particles coated with an antibody to mesothelin (APMS-MB) against particles coated with a control protein, bovine serum albumin (APMS-BSA). Mesothelin is a protein found on many mesothelioma cells. At 6 days, tumors held 12% of the injected APMS-MB particles versus 8% of the APMS-BSA particles. The authors reported this difference as statistically significant. The particles carried no drug in these experiments. The authors concluded that antibody-coated particles could be both imaged and targeted to tumors in this mouse model.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: particle distribution in healthy rats and in a mouse xenograft model of human malignant mesothelioma, with supporting cell-culture work
• Who was studied: Healthy Wistar rats (n=3 for organ and urine analysis) given 500 mg/kg particles into the peritoneal cavity. Male 6-week-old Fox Chase SCID mice injected in the peritoneal cavity with human PPM Mill mesothelioma cells. Particle groups were 5 mice per group for saline and APMS-MB, and 4 mice per time point for APMS-BSA. Human mesothelioma cell lines were also tested in vitro.
• Exposure: Acid-prepared mesoporous spheres (APMS), amorphous silica microparticles 1 to 2 micrometres across. They were labelled with gadolinium or fluorescent dye and coated either with an anti-mesothelin antibody (MB) or with bovine serum albumin (BSA); saline was the control. No drug was loaded and asbestos was not studied.
• Main results:
  • In healthy Wistar rats, gadolinium-labelled particles were found in urine from 0.5 to 24 hours.
  • In the same rats, no particles were found in urine at 144 hours (6 days).
  • Only four of seven mesothelioma cell lines grown in the laboratory showed mesothelin protein on Western blots.
  • In tumor-bearing mice at 24 hours, more than 6% of the injected particle dose was in the pooled tumors for both APMS-MB and APMS-BSA. Less than 2% was in the lungs, liver, spleen and kidneys.
  • In tumor-bearing mice at 6 days, about 3.5% of the injected amount was in the liver.
  • At 6 days, tumors retained 12% of the injected dose of antibody-coated APMS-MB, which the authors reported as significantly higher than the 8% retained for control APMS-BSA.
  • At 6 days, the silica concentration in tumor tissue was significantly greater with APMS-MB than with APMS-BSA. The results section specifies mesenteric tumors.
  • At 24 hours after injection, there were no significant differences between groups in inflammatory cell counts in peritoneal lavage fluid.
  • At 24 hours, spheroid tumors in both particle-treated groups showed a significant reduction in tumor-associated macrophage burden compared with saline controls.
• The authors' conclusion: The authors concluded that APMS particles coated with an antibody to mesothelin are a delivery device that can be both imaged and targeted to tumors in this mouse model of peritoneal mesothelioma.
• Limitations the authors state:
  • Experimental problems left only one saline-group animal at 24 hours, so statistical significance could not be calculated for that group.
  • The role of tumor-associated macrophages in mesothelioma and in moving the particles is unclear.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelin, Mesothelioma, Peritoneal Mesothelioma, Peritoneal Cavity, Encapsulation.

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