Photodynamic drug delivery enhancement in tumours does not depend on leukocyte-endothelial interaction in a human mesothelioma xenograft model

Our plain-English summary of Photodynamic drug delivery enhancement in tumours does not depend on leukocyte-endothelial interaction in a human mesothelioma xenograft model, by Y. Wang, J.Y. Perentes, S.C. Schäfer, et al (European Journal of Cardio-thoracic Surgery, 2012).

The study

• Authors: Y. Wang, J.Y. Perentes, S.C. Schäfer, M. Gonzalez, E. Debefve, H.A. Lehr, H. van den Bergh, T. Krueger
• Journal: European Journal of Cardio-thoracic Surgery
• Published: 2012;42(2):348-54
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: The pre-treatment of tumour neovessels by low-level photodynamic therapy (PDT) improves the distribution of concomitantly administered systemic chemotherapy. The mechanism by which PDT permeabilizes the tumour vessel wall is only partially known. We have recently shown that leukocyte-endothelial cell interaction is essential for photodynamic drug delivery to normal tissue. The present study investigates whether PDT enhances drug delivery in malignant mesothelioma and whether it involves comparable mechanisms of actions.

Methods: Human mesothelioma xenografts (H-meso-1) were grown in the dorsal skinfold chambers of 28 nude mice. By intravital microscopy, the rolling and recruitment of leukocytes were assessed in tumour vessels following PDT (Visudyne(®) 400 μg/kg, fluence rate 200 mW/cm(2) and fluence 60 J/cm(2)) using intravital microscopy. Likewise, the distribution of fluorescently labelled macromolecular dextran (FITC-dextran, MW 2000 kDa) was determined after PDT. Study groups included no PDT, PDT, PDT plus a functionally blocking anti-pan-selectin antibody cocktail and PDT plus isotype control antibody.

Results: PDT significantly enhanced the extravascular accumulation of FITC-dextran in mesothelioma xenografts, but not in normal tissue. PDT significantly increased leukocyte-endothelial cell interaction in tumour. While PDT-induced leukocyte recruitment was significantly blunted by the anti-pan-selectin antibodies in the tumour xenograft, this manipulation did not affect the PDT-induced extravasation of FITC-dextran.

Conclusions: Low-level PDT pre-treatment selectively enhances the uptake of systemically circulating macromolecular drugs in malignant mesothelioma, but not in normal tissue. Leukocyte-endothelial cell interaction is not required for PDT-induced drug delivery to malignant mesothelioma.

In plain English

This was a laboratory experiment in mice. It did not study asbestos exposure. The authors used 28 nude mice with skin chambers on their backs; 23 carried human mesothelioma tumour tissue (cell line H-meso-1) and 5 had normal tissue only. They tested whether low-level photodynamic therapy (PDT), a light-activated drug treatment using Visudyne, helps a large fluorescent test molecule (FITC-dextran) leak from blood vessels into tumour tissue. They also tested whether white blood cells sticking to vessel walls are needed for this. PDT significantly increased leakage into mesothelioma tissue, but not into normal tissue given the same treatment. Over 45 minutes, the normalized fluorescent signal (arbitrary units) in the treated tumour zone rose roughly 1000-fold. PDT also significantly increased white blood cell rolling and recruitment in the treated tumour area. Antibodies that block selectins significantly reduced this white blood cell activity but did not stop the increased leakage. The authors concluded that low-dose PDT selectively increased delivery to mesothelioma xenografts, and that white blood cell–vessel wall interaction was not required.

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 (human mesothelioma tumour tissue grown in mice, observed by intravital fluorescence microscopy)
• Who was studied: 28 nude mice with dorsal skinfold chambers, of which 23 carried human mesothelioma xenografts (cell line H-meso-1). 23 mice received low-level PDT: 8 had PDT only, 5 had PDT plus anti-selectin antibodies, 5 had PDT plus isotype control antibody, and 5 had PDT on normal tissue with no tumour. A further 5 tumour-bearing controls received Visudyne without light.
• Exposure: No asbestos exposure was studied. The intervention was Visudyne-mediated low-level photodynamic therapy (400 μg/kg body weight, light dose 60 J/cm2, fluence rate 200 mW/cm2), followed 1 hour later by intravenous FITC-dextran (2000 kDa). Some groups also received an anti-pan-selectin antibody cocktail or an isotype control antibody.
• Main results:
  • PDT significantly enhanced FITC-dextran extravasation in mesothelioma tumour tissue, but not in normal tissue given the same drug and light dose
  • Over the 45-minute observation period, the intensity of the fluorescent signal in the PDT-treated zone of the mesothelioma xenografts increased roughly 1000-fold (arbitrary units, normalized data)
  • PDT on normal tissue (striated muscle and fat) under the same conditions had no effect on FITC-dextran extravasation
  • In tumours, PDT alone and PDT plus isotype antibody significantly increased leukocyte rolling and their recruitment to the PDT-treated area for up to 2 hours after treatment
  • The anti-pan-selectin antibody cocktail significantly reduced PDT-induced leukocyte rolling and recruitment
  • FITC-dextran extravasation was significantly enhanced in all PDT-treated tumour groups, whether the isotype antibody or the blocking anti-selectin antibodies were given
• The authors' conclusion: The authors concluded that low-level PDT selectively enhanced uptake of circulating macromolecular drugs in malignant mesothelioma xenografts but not in normal tissue, and that leukocyte–endothelial cell interaction was not required for this effect

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Chemotherapy, Malignant Mesothelioma.

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