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

Abstract

Background: 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 T 1 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 H 2 O 2 into O 2 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.

Advances of Nanomedicine in Radiotherapy

“…The fHMNM containing catalase-like Mn(III)-porphyrin ligand can degrade hydrogen peroxide to oxygen, improve tumor tissue hypoxia, and enhance the sensitivity of PTT and RT. In mouse cancer models, synergistic thermo-radiotherapy modulated by fHMNM significantly inhibited the growth of tumor tissue, with no obvious toxic reaction [103].…”

“…Due to their efficient heat generation abilities and X-ray attenuation coefficient, other heavy metal-based nanocomposites, such as Bi 2 Se and BiP 5 , have been developed as enhancers for synergistic thermo-radiotherapy [95,[103][104][105][106]. For example, Zhou et al developed an effective radiosensitizer, which was named bismuth heteropolytungstate (BiP 5 W 30 ) nanoclusters.…”

Metal-Organic Frameworks and Their Composites Towards Biomedical Applications

“…Signals from CT and MR were increased by 1.7-fold and 3-to 5-fold, respectively. Thus, this triple-modality imaging-assisted PTT/RT system showed high potential in tumor theranostics (Bao et al, 2020).…”

“…Many cancer cells, including breast, cervical, colorectal, ovarian cancer cells, express a high level of folate receptors (FRs) on their cell surface, and folic acid (FA) is a universally studied targeting agent. As moiety provides ease of modification, FA could bind to various nano-MOFs through interaction between carboxylic groups of FA and positive moieties, such as Hf 6 cluster of Hf-Mn-NMOF (Bao et al, 2020), amino groups of Uio-66-NH 2 , and IRMOF-3 (Yang et al, 2017a;Gao et al, 2018b). Besides, FA could also be grafted to MOFs through intermediates, exemplified by binding FA to PEI on the surface of gadolinium-porphyrin MOFs (FA-NPMOFs) (Chen et al, 2019b).…”

Metal-Organic Frameworks for Bioimaging: Strategies and Challenges

“…Based on the targeted mediated imaging, the imaging mode gradually changes from dual-modal to three modal [103].…”