Multifunctional Hf/Mn-TCPP Metal-Organic Framework Nanoparticles for Triple-Modality Imaging-Guided PTT/RT Synergistic Cancer Therapy

Jianfeng Bao,1,2 Xiangyang Zu,2 Xiao Wang,1 Jinghua Li,2 Dandan Fan,3 Yupeng Shi,1 Qingchun Xia,4 Jingliang Cheng1 1Functional Magnetic Resonance and Molecular Imaging Key Laboratory of Henan Province, Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2College of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, Henan, People’s Republic of China; 3Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 4Henan Key Laboratory of Boron Chemistry and Advanced Energy Materials, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan, People’s Republic of ChinaCorrespondence: Jingliang ChengThe First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaTel +86-13603863860Fax +86-37166964992Email cjr.chjl@vip.163.comQingchun XiaHenan Normal University, Xinxiang, Henan, People’s Republic of ChinaTel +86-13353679807Fax +86-3733329030Email xiaqingchun@htu.edu.cnBackground: Recent studies have validated and confirmed the great potential of nanoscale metal-organic framework (NMOF) in the biomedical field, especially in improving the efficiency of cancer diagnosis and therapy. However, most previous studies only utilized either the metal cluster or the organic ligand of the NMOF for cancer treatments and merely reported limited theranostic functions, which may not be optimized. As a highly designable and easily functionalized material, prospective rational design offers a powerful way to extract the maximum benefit from NMOF for cancer theranostic applications.Materials and Methods: A NMOF based on hafnium (Hf) cluster and Mn(III)-porphyrin ligand was rational designed and synthesized as a high-performance multifunctional theranostic agent. The folic acid (FA) was modified on the NMOF surface to enhance the cancer targeting efficacy. The proposed “all-in-one” FA-Hf-Mn-NMOF (fHMNM) was characterized and identified using various analytical techniques. Then, in vitro and in vivo studies were performed to further explore the effects of fHMNM both as the magnetic resonance imaging (MRI)/computed tomography (CT)/photoacoustic imaging (PAI) contrast agent and as the photothermal therapy (PTT)/radiotherapy (RT) agent.Results: A tumour targeting multifunctional fHMNM was successfully synthesized with high performance for MRI/CT/PAI enhancements and image-guided PTT/RT synergistic therapy properties. Compared with the current clinical CT and MR contrast agents, the X-ray attenuation and T1 relaxation rate of this integrated nanosystem increased 1.7-fold and 3– 5-fold, respectively. More importantly, the catalase-like Mn(III)-porphyrin ligand can decompose H2O2 into O2 in tumour microenvironments to improve the synergistic treatment efficiency of PTT and RT. Significant tumour growth inhibition was achieved in mouse cancer models without obvious damage to the other organs.Conclusion: This work highlights the potential of fHMNM as an easily designable material for biomedical applications, could be an effective tool for in vivo detection and subsequent treatment of tumour.Keywords: metal-organic framework, theranostics, multimodality imaging, radiotherapy, photothermal therapy