Preclinical evaluation of arsenic trioxide in nanoparticle formulation for sonic hedgehog activated atypical teratoid rhabdoid tumors
Atypical teratoid/rhabdoid tumors (AT/RT) are aggressive embryonal brain tumors. In one distinct subgroup of AT/RT, the sonic-hedgehog (SHH), the signaling pathway is activated downstream of the trans membranous receptors. We recently discovered that arsenic trioxide (ATO) inhibits the SHH-signaling downstream which made ATO therapeutically interesting. Even though ATO has been successfully introduced into clinical treatment of leukemia, numerous clinical trials in solid tumors failed due to insufficient drug concentrations in the tumor tissue. In this project we focus on developing nanocarriers for drug delivery of ATO, which (i) cross the blood brain barrier, (ii) deliver ATO and release it in the tumor tissue, (iii) avoid toxic concentration in organs, and (iv) can be monitored by MRI.
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