Microbeam Radiation Therapy-induced vascular permeability window and nanoparticle-enhanced therapy
Djonov group Prof. Dr. med. Valentin Djonov
Microbeam Radiation Therapy delivers arrays of ultra-narrow X-ray beams that generate steep dose heterogeneity within tissues.
This geometry allows exceptional normal-tissue tolerance while maintaining strong tumour control.
Our research investigates how Microbeam Radiation Therapy temporarily increases tumour vascular permeability, creating a “permeability window” that enables enhanced delivery of nanoparticles or therapeutic agents.
Using synchrotron microbeam arrays in melanoma models, we demonstrated that a priming exposure of 150 Gy increases intratumoural gold-nanoparticle accumulation more than twofold and, when combined with a therapeutic microbeam dose (400 Gy peaks), significantly delays tumour growth and extends survival.
Image Mass Cytometry revealed nanoparticle localisation near tumour vessels and in M2-like macrophages, confirming a transient vascular-permeability mechanism.
This project builds on the first report of this phenomenon (Sabatasso et al., Cancers 2021; DOI: 10.3390/cancers13092103), which established a 15-min to 4-h permeability window suitable for adjuvant delivery, and the concept is protected under patent ref. P166072 (“Microbeam Radiation Therapy–induced vascular permeability window for drug delivery”).
We are now defining the dosimetric and biological parameters that govern this effect and testing whether similar windows can be achieved with compact sub-millimetre sources compatible with clinical translation.
Our long-term goal is to integrate this mechanism into combination radiotherapies that enhance radiosensitisation, immunotherapy efficacy, and targeted drug delivery in radio-resistant tumours.

