Versatile Application of Nanoscale Metal-Organic Frameworks for Intratumoral Delivery

Recent preclinical and clinical studies have highlighted the improved outcomes of combination radiotherapy and immunotherapy. Concurrently, the development of high atomic number (high-Z) metallic nanoparticles as radiation dose enhancers has been explored to widen the therapeutic window of radiotherapy and potentially enhance immune activation. Due to their high X-ray attenuation and high density, metal-based nanoparticles also have the potential to serve as imaging agents. Exploiting high-Z metal nanoparticles would provide clinical advantages for image-guided radiotherapy for targeted cancer treatment.
Despite the numerous advances in the field of drug delivery, there are still unmet needs that could lead to the development of a therapeutic molecule delivery carrier. In this study, we seek intraturmoral delivery of metal-organic frameworks to induce a robust stimulation of anticancer immunity for a systemic and long-lasting therapeutic benefit. By utilizing hafnium and iron-based metal-organic frameworks, we target immune cells with other targeted cancer therapies for synergistic advantages. We employ this nanomaterial as a pharmaceutical carrier system for the delivery of a wide range of materials, from small molecules to macromolecules. Radiotherapy-induced local tissue damage and inflammation have the potential to generate tumor antigen and release danger-associated molecular patterns. Nanoscale metal-organic frameworks are a versatile platform for combination radiotherapy. In addition to serving as drug carriers, our high-Z metal-organic frameworks are attractive nanomaterials that serve as contrast agents in biomedical imaging. We conducted phantom studies in vitro and in vivo, using microCT for real-time monitoring, which will facilitate advanced analysis of tumor cells and their responses to therapy. Intratumoral immunotherapy provides the capacity to manipulate the tumor microenvironment by targeting cells within the tumor microenvironment, making it an attractive therapeutic approach.