Due to their intrinsic properties, nanoscale metal-organic frameworks (nMOFs) have been widely researched as drug delivery vehicles and contrast agents in cancer therapy. More recently, the ability of these nMOFs to interact with external stimuli has attracted significant attention, specifically in radiation-based approaches. Modification of both the ligand and the metal component allows these MOFs to be constructed and tuned for these specific applications to develop novel therapeutic platforms. As such, we have evaluated them for applications in both radiation therapy (RT) and imaging. For instance, upon exposure to RT, certain (high Z-element) nMOFs can generate increased levels of reactive oxygen species (ROS), resulting in increased DNA damage, a key component of effective therapy. Combining radiation enhancing nMOFs with complementary chemotherapeutics can greatly enhance their synergistic activity, thereby enhancing therapeutic efficacy. Here, we create a unique therapeutic model by synthesizing a nMOF containing the high Z-element hafnium (Hf) and the ligand 1,4-dicarboxybenzene (Hf-BDC) and incorporating two DNA damage repair (DDR) inhibitors, talazoparib and buparlisib (TB@Hf-BDC-PEG). <i>In vitro,</i> TB@Hf-BDC-PEG both augmented RT by increasing ROS generation (DNA damage) and inhibited DNA repair thereafter through the release of the DDR inhibitors, underscoring its complementary activity. Therapeutic potential was further supported upon translation to an <i>in vivo </i>breast cancer model where the combination of RT with TB@Hf-BDC-PEG resulted in increased apoptosis and decreased proliferation, supporting its synergistic activity and potential as a therapeutic platform. Furthermore, we evaluate certain lanthanide-based MOFs and their potential utilization as contrast-based agents through X-ray excited radioluminescence imaging.

Metal-organic frameworks for radiation-based cancer therapies

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.