Technology Description
This licensing and collaborative research opportunity relates to a synergistic treatment strategy for enhancing the therapeutic efficacy of radiotherapy (RT) via nMOF-mediated drug delivery and RT enhancement. nMOF containing the high-Z element Hf and the ligand 1,4-dicarboxybenzene (Hf-BDC) was synthesized and loaded with two DNA damage repair (DDR) inhibitor drugs, talazoparib and buparlisib (TB@Hf-BDC-PEG). TB@Hf-BDC-PEG augmented RT by increasing reactive oxygen species generation and thus DNA damage of which repair was inhibited thereafter. Synergistic enhancement was demonstrated in vivo where the combination of concurrent radiation with intravenous TB@Hf-BDC-PEG administration resulted in improved tumor control and increased apoptosis. Importantly, no apparent toxicity was observed with nMOF treatment, supporting its potential as an attractive candidate over traditional nanomaterials. Polysaccharide coated second generation materials exhibit enhanced uptake in irradiated cells.
Features & Benefits
Due to their complementary activity, the use of DDR inhibitors during RT has yielded promising results. Unfortunately, this approach is often hindered by toxicity and poor in vivo stability of the DDR inhibitors. Nanoscale metal–organic frameworks (nMOFs) represent an emerging class of crystalline materials which exhibit advantageous properties over traditional nanomaterials and demonstrate great potential in oncology.
Patent Pending (U.S. provisional patent application)
nMOFs coated with fucoidan show enhanced uptake in irradiated cancer cells (left) and enhanced IR toxicity (right). [Radiation dose: 2 GyCell Line: CT26, murine colorectal]