Convection-enhanced delivery (CED) of siRNA-bearing nanoparticles for brain cancer therapy and the control of its appropriate implementation by positron emission tomography and magnetic resonance imaging (PET-MRI)
Glioblastoma multiforme is the most aggressive type of primary brain tumours with a median overall survival (OS) of about 12 months. Treatment of those tumours remains one of the most challenging tasks in clinical oncology. Although new molecular pathways in tumour biology are being constantly discovered, translation of basic science achievements into clinical practice is rather slow. Major obstacles in resistance to therapy are heterogeneity of brain tumours, multiple genetic alterations, and their diffuse, infiltrative behaviour. Convection-enhanced delivery (CED) is a broadly applicable technique that can be used to deliver drugs under a slight pressure gradient directly into the interstitial spaces of the central nervous system. Accordingly it is a promising concept for the treatment of malignant gliomas, which will be used in the current project in combination with the application of nanoparticles. Ideally those nanoparticles are small (< 100 nm) and less adhesive (hydrophilic surface). It is planned to functionalize the nanoparticles with small interfering RNA (siRNA), also known as silencing RNA, which hinders the expression of specific genes with complementary nucleotide sequences by degrading the mRNA after transcription, thus preventing translation. For the in vivo application of such therapy concept an orthologue model of glioma will be established in rats. The success of the application of the nanoparticles and their distribution in the tumour and in the CNS in dependence on time and structure of the nanoparticles will be investigated with positron emission tomography and magnetic resonance imaging (PET-MRI).
The principle of convection-enhanced delivery of functionalized nanoparticles and the measurement of their distribution in brain tumours with positron emission tomography (modified from Sirianni et al., 2014)
Universität Leipzig, Institute of Pharmacy (Prof. Michaela Schulz-Siegmund)
- EFRE (European Regional Development Fund) together with the Free State of Saxony
- Mitrach F et. al. (2022) Amphiphilic Anionic Oligomer-Stabilized Calcium Phosphate Nanoparticles with Prospects in siRNA Delivery via Convection-Enhanced Delivery. Pharmaceutics 29;14(2):326.