HyGlio · Theranostic Injectable Hydrogel for Glioblastoma

Theranostic Injectable Hydrogel for Glioblastoma

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. Its infiltrative nature, ability to mutate into newer and more aggressive tumor variants, and the location behind a partially-intact blood brain barrier, make this tumor extremely difficult to treat via systemic chemotherapy and invariably fatal. This project aimed at designing a biomaterials-based approach for direct intra-cranial (IC) drug delivery to brain tumors. To achieve this goal, a multi-component system composed of nanoparticles and a hydrogel for enhanced intra-cranial treatment retention, was designed and characterized. Drug and particle distribution and retention in the brain after IC injection were also characterized in vivo on tumor-free and tumor-bearing mice, using fluorescent drug surrogates and fluorescent-tagged nanoparticles. The overall objectives of HyGlio were: 1.To optimize nanoparticles design to maximize drug loading and tumor targeting 2. To design IC drug delivery systems 3. To analyze brain distribution and retention of IC-injected nanoparticles or nanoparticles embedded in injectable hydrogels 4. To validate the system in an intra-cranial model of GBM in mice In conclusion, the results achieved in this project showed that hydrogels enhance the retention of nanoparticles in the brain of tumor-bearing mice, and increased the tumor coverage. Moreover, tumor treatment with drug loaded nanoparticles resulted in enhanced survival of tumor bearing mice and in reduced toxicity of the encapsulated drug. We also determined that after drug treatment, modifications in number and structure of tumor blood vessels as well as over-expression of TWIST (indicative of epithelial to mesenchymal transition) occurred.

Data: CORDIS, © European Union