Nanoparticle diagnostics, detection of glioblastoma cells in human brain biopsies
The project is = to create improved diagnostics for human erbB over-expressing tumors.
In collaboration with neurosurgeons at the University of Göttingen Medical School we have produced specifically conjugated quantum dots that targeted Her1 expression which is upregulated on greater than 30% of all human gliomal brain tumors. Both Mab- and EGF- (epidermal growth factor) coupled QDs specifically recognized not only high-grade glioma biopsies but also were able to distinguish tumor cells in low-grade biospies where no gadolinium positive signal can be visualized. Excellent delineation of tumor tissue from normal brain in fresh biopsies was achieved even in the case of low-grade tumors. The results of the high grade tumor protocol was published in 2009 in IEEE Transactions in Nanobioscience and the protocol for low-grade tumors was published in PLoS ONE in June 2010, http://dx.plos.org/10.1371/journal.pone.0011323. The success of the protocol has allowed the clinical collaborators to propose a Phase 1 assessment of this diagnostic for patients in the near future.
We have also been able to target both resistant and sensitive Her2 expressing breast tumor cells with specific affibody-conjugated probes formulated in collaboration with the group of Manfred Konrad, MPIBPC. A conjugated prodrug converting enzyme and affibody construct were internalized by the Her2 expressing tumors. In order to increase the level of enzyme available for prodrug conversion a microcapsule technique is on-going and the goal is to produce a vehicle that would target the Her2 cells and make them more sensitive to chemotherapy.
The clinical application of the diagnostics developed in the project will benefit the citizens of the EU by helping to raise life-expectancy for patients with glioblastoma brain tumors.
A. T-1weighted MRI brain scan with no gadolinium positive signal of a grade II oligodendroma. (B-E) Digital macrophotographic images of ex vivo stained biopsies from the resected tumor stained with targeted (B-D) QD probes or (E) untargeted QDs taken with the same magnification and the same exposure times.
