Prof. Jun-Jie Zhu's research group from the School of Chemistry and Chemical Engineering has recently made important progress in the research of metal–organic framework nanomaterials for multimodal cancer treatment. Their research paper A Catalase-Like Metal–Organic Framework Nanohybrid for O2-Evolving Synergistic Chemoradiotherapy was published online in Angew. Chemie (https://doi.org/10.1002/anie.201902612) on May 2, 2019. This work was completed in cooperation between Jun-Jie Zhu's group and Xiaoyuan Chen's group of the National Institutes of Health. Dr. Zhimei He, Dr. Chen Wang from the School of Life Sciences and Dr. Xiaolin Huang from Nanchang University are the co-first authors. Prof. Jun-Jie Zhu, Prof. Yunlu Dai from the University of Macau, Dr. Guocan Yu and Prof. Xiaoyuan Chen from the National Institutes of Health are the co-corresponding authors. And Nanjing University is the first communication institution.
Recently, Prof. Jun-Jie Zhu and Prof. Xiaoyuan Chen have made a series of advances in biomarker detection and nanotheranostics (Theranostics 2018, 8, 3461–3473; Small 2019, 15, e1804131). Hypoxia, a phenotype of inadequate O2 supply in fast-growing tumors due to the aberrant and tortuous tumor vasculature, is highly responsible for tumor migration, invasion, metastasis, and resistance to different therapies, which impairs the outcomes of O2-dependent photodynamic therapy and radiotherapy. The common strategies for improving the sensitivity of hypoxic cells to radiotherapy are 1) elevating the O2 content at the tumor; 2) high-Z materials (e.g., Au, Bi, Hf) with large X-ray attenuation coefficient facilitate the efficient deposition of irradiation energy within the tumor, making the best utilization of radiation.
In the clinic, radiotherapy is usually utilized as an adjuvant tool to combine with surgery or chemotherapy to lessen the chance of tumor recurrence. So far, although continuous efforts have been invested in the combined chemoradiotherapy, their antitumor performances are often unsatisfactory due to tumor resistance to treatments.
To overcome this problem, the above two research groups worked closely to propose an in situ catalytic oxygenation strategy in tumor using porphyrinic metal–organic framework (MOF)-gold nanoparticles (AuNPs) nanohybrid as a therapeutic platform to achieve O2-evolving chemoradiotherapy. In this work, the modification of AuNPs introduces the following advantages: 1) sensitizing hypoxic cancer cells to X-rays; 2) making MOF highly stable to prevent premature degradation during drug delivery; 3) endowing MOF with catalase-like activity, which effectively improves the tumor oxygenation by catalyzing the tumor metabolite H2O2 into O2, thus improving the efficacy of O2-dependent radiotherapy. Interestingly, the MOF-Au NPs still maintain the highly porous structure of MOF, which favors the efficient encapsulation of anticancer drug. In vitro and in vivo studies have demonstrated that the nanocomposites with radiosensitization effect exhibited good antitumor performance, providing a novel strategy for multimodal cancer treatment. This research work was supported by the National Natural Science Foundation of China (21834004, 21427807), International Cooperation Foundation from Ministry of Science and Technology (2016YFE0130100), China Postdoctoral Science Foundation (2018M640472), etc.