Combination cancer therapies often offer improved tumor cell kill over individual treatments, such as surgery, radiation, or chemotherapy alone. However, these multi-pronged approaches may also increase unwanted toxicities for the patient. In an effort to reduce these limiting side-effects, nanoparticle drug carriers have been investigated for site specific and controlled release of therapeutic agents. In our previous work, we have developed a variety of polymeric, inorganic, and composite nanomaterials capable of delivering hydrophilic or hydrophobic chemotherapeutic compounds to cancer cells. Here, we present a metal-organic framework (MoF) nanoparticle platform for the delivery of DNA damage repair inhibitors, such as the poly-ADP ribose polymerase (PARP) inhibitor, talazoparib, to breast cancer cells.  We have engineered a carrier that is capable of loading these drugs and demonstrate their release as well as the ability of the hafnium(BDC) MoF to serve as a radiation dose enhancer. The hydrodynamic size of the drug loaded particles were approximately 100 nm and correlated well with that observed by TEM. The resulting nanoparticles were evaluated for efficacy against a breast cancer cell line, 4T1, to assess cytotoxicity in vitro. Preliminary chemoradiation studies were also performed with the MoFs by assessing DNA damage via the ?H2AX assay on this cell line. In addition, short and long-term biocompatibility studies were performed, as well as the biodistribution of PEGylated MoF nanoparticles were evaluated in a mouse model by inductively coupled plasma mass spectrometry (ICP-MS). Overall, these results provide a strong foundation for the further development of this nanoparticle-based drug delivery platform for chemoradiation of breast cancers.        <br/>

Engineering metal-organic-framework nanoparticles for enhanced chemoradiation of breast cancer

2019 Fall National Meeting

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