Of all pediatric cancers, diffuse intrinsic pontine glioma (DIPG) is the most aggressive. Focal radiotherapy only prolongs patient survival for a few months. Chemotherapy does not improve patient survival as DIPG is intrinsically resistant to most chemotherapeutics. Furthermore, our brains naturally prevent most drugs from reaching the brain tumor. Convection-enhanced delivery (CED), is a direct infusion technique for delivering drugs to the brain. However, drug molecules can be rapidly cleared from the brain immediately after CED delivery. The physicochemical properties of the nanofiber platform (NFP) can be fine-tuned to control post-CED tissue distribution and retention. The Law lab uses a combination of CED and NFP to bypass the blood brain barrier (BBB), prolong drug retention at the fusion site, and maintain an effective therapeutic effect against DIPG to improve treatment outcome.
Related Publications:
(1) Bellat V., et al., A combined approach of convection-enhanced delivery of peptide nanofiber reservoir to prolong local DM1 retention for diffuse intrinsic pontine glioma treatment, Neuro-Oncol., 22(10):1495-504: 2020.
(2) Tosi U., et al., Real-Time, in Vivo Correlation of Molecular Structure with Drug Distribution in the Brain Striatum Following Convection Enhanced Delivery, ACS Chem. Neurosci, 10(5):2287-98: 2019.
(3) Kommidi H., et al., (18)F-Radiolabeled Panobinostat Allows for Positron Emission Tomography Guided Delivery of a Histone Deacetylase Inhibitor, ACS Med. Chem. Lett., 9(2):114-9: 2018.
(4) Wang M., et al., A Murine Model for Quantitative, Real-Time Evaluation of Convection-Enhanced Delivery (RT-CED) Using an (18)[F]-Positron Emitting, Fluorescent Derivative of Dasatinib, Mol. Cancer Ther., 16(12):2902-12: 2017.
(5) Singh R., et al., Volume of distribution and clearance of peptide-based nanofiber after convection-enhanced delivery, J. Neurosurg., 129(1):10-8: 2018.