Within this doctoral thesis, an easy implementable and broadly available method was developed to predict the accumulation of nanomedicines in tumors. By immunohistological staining of biopsies and quantifying blood vessels and macrophages, it is possible to differentiate tumors with regard to their nanomedicine accumulation, which has the potential to be used cost-effectively in clinical trials as an inclusion vs. exclusion criterion. To this end, suitable biomarkers were first investigated in preclinical tumor models and a duo was identified with blood vessels and macrophages, which was subsequently validated both in preclinical tumor models and on patient material - both from resections and biopsies. Additionally, optical imaging modalities were used to investigate the transport of fluorescently labeled nanocarriers into the brain of healthy mice. The extent to which the opening of the blood-brain barrier with ultrasound and microbubbles enables the extravasation of the drug delivery systems from the blood vessels into the brain was compared. Using micro- and nanoscopy, a size-dependent effect was demonstrated, as the smaller polymeric nanocarrier (10-20 nm) extravasated more frequently and more deeply from the blood vessels than the larger liposomes (100-120 nm). When developing nanomedicines for the treatment of diseases of the central nervous system, the size should therefore also be taken into account, whereby the balance between optimal distribution in the brain tissue and sufficient drug loading should be maintained. The clinical translation of nanomedicines could be more successful. By implementing pragmatic protocols for stratifying patients or using methods for opening the blood-brain barrier, a higher accumulation of nanomedicinal drug carriers in (brain) tumor tissue can be made possible and therapies improved.
Jan-Niklas May (Wed,) studied this question.