Cellular fate and performance of group IV metal organic framework radioenhancers

Neuer, Anna Lena; Jessernig, Alexander; Gerken, Lukas R. H.; Gogos, Alexander; Starsich, Fabian H. L.; Gschwend, Pascal M.; Herrmann, Inge K.

doi:10.1039/d2bm00973k

Cited by 9 publications

(24 citation statements)

References 52 publications

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“…This is well in line with previous results indicating increased tolerance of NHDF cells towards oxidative stress. 40,41 With regard to the long-term viability (see Fig. 2b,c), reduction in viability was more pronounced compared to the 24 hours timepoint for both the fresh MXenes, with 6-day viabilities of ~70% for doses of 20 µg/ml (compared to >95% at 24h) and aged MXenes with >65% viability for doses of 40 µg/ml (compared to unaffected cell viability at the 24h time point).…”

Section: Cytocompatibility Uptake and Cellular Fate Of Mxenesmentioning

confidence: 95%

Radiotherapy Enhancement by Ti3C2Tx MXenes

Zimmermann

Gerken

Wee

et al. 2023

Preprint

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Radiotherapy is an integral part of cancer therapy. Due to the low tissue specificity of radiation, damage to tumor-surrounding healthy tissue remains a major concern. Radio-enhancers based on inorganic nanomaterials have attracted considerable attention in recent years. In addition to widely exploited metal and metal oxides nanoparticles, 2D materials may offer potential advantages due to their intrinsically high specific surface area. Here, we report on the promising radio-enhancement properties of Ti3C2Tx MXenes. We show that Ti3C2Tx MXenes are readily internalized and well-tolerated by mammalian cells. In contrast to MXenes suspended in aqueous buffers which fully oxidize within days (yielding rice-grain shaped rutile nanoparticles), MXenes internalized by cells display slower oxidation rates, in line with cell-free experiments showing slower oxidation in cell media and lysosomal buffers compared to antioxidant-devoid dispersants. The MXenes show potent radio-enhancement properties with dose enhancement factors of up to 2.5 in human soft tissue sarcoma cells and no toxicity towards healthy human fibroblasts. Benchmarking against oxidized MXenes and commercial titanium dioxide nanoparticles indicates superior radio-enhancement properties of the intact 2D titanium carbide flakes. Taken together, this work provides direct evidence for the potent radio-enhancement properties of Ti3C2Tx MXenes rendering them a promising candidate material for radiotherapy enhancement.

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Section: Cytocompatibility Uptake and Cellular Fate Of Mxenesmentioning

confidence: 95%

Radiotherapy Enhancement by Ti3C2Tx MXenes

Zimmermann

Gerken

Wee

et al. 2023

Preprint

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“…NanoMOF Synthesis and Characterization: Hf-DBA, Hf-TCPP, Ti-MIL, and TiZr-PCN were synthesized following previously published procedures. [39] For scanning transmission electron microscopy (STEM) characterization, 500 μL of 0.1 mg mL −1 particle suspension in ethanol was centrifuged onto copper grids (EMR, Holey Carbon Film 200 Mesh) for 10 min at 21.000 × g and analyzed with a Hitachi S-4800 (Hitachi) scanning electron microscope. The images were also used for size distribution measurement using the Fiji-ImageJ software (2.1.0/1.53c / Java 1.8.0_172).…”

Section: Methodsmentioning

confidence: 99%

“…To demonstrate the performance of our co-culture model, we investigated the radio-enhancement properties of a selection of group IV nanoMOFs, which are promising radio-enhancers candidate materials, [39] in direct comparison to commercially available 50-nm gold nanoparticles, which are the current gold-standard material for radio-enhancement in 2D and 3D. [5,30] Group IV nanoMOFs, including the high-Z Hf-containing Hf-DBA and Hf-TCPP, as well as the lower-Z Ti-containing Ti-MIL and TiZr-PCN, exhibited primary particle sizes in the range from 100 to 500 nm for their average diameter (Figure 2A,B, also see Figure S1, Supporting Information for histogram size distribution), with Hf-DBA being the smallest with 101 ± 22 nm, followed by Ti-MIL with 191 ± 39 nm, and TiZr-PCN with 281 ± 47 nm, and Hf-TCPP being the largest with 496 ± 116 nm.…”

Section: Nano-sized Radio-enhancer Candidate Materialsmentioning

confidence: 99%

“…[40] In HT1080 cells, 3D spheroids have overall lower radio enhancement effects compared to previously published effects in 2D monolayer scenarios were DMR 50% up to 3.8 were found (treatment concentration 40 μg mL −1 ). [39] Generally, more complex 3D tissues with cell-cell interaction scenarios are believed to have a higher radio-resistance in comparison to 2D monolayer cells without tighter cell-cell interactions. [41] This higher resistance was previously explained, for example, with changes in cell cycle regulation, gene expression, and chromatin density modifications.…”

Section: Nre-based Radio-enhancement Normal Tissue Toxicity and Thera...mentioning

confidence: 99%

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Metal–Organic Framework Mediated Radio‐Enhancement Assessed in High‐Throughput‐Compatible 3D Tumor Spheroid Co‐Cultures

et al. 2023

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Inorganic nanomaterials have gained increasing attention in radiation oncology, owing to their radiation therapy enhancing properties. To accelerate candidate material selection and overcome the disconnect between conventional 2D cell culture and in vivo findings, screening platforms unifying high‐throughput with physiologically relevant endpoint analysis based on 3D in vitro models are promising. Here, a 3D tumor spheroid co‐culture model based on cancerous and healthy human cells is presented for the concurrent assessment of radio‐enhancement efficacy, toxicity, and intratissural biodistribution with full ultrastructural context of radioenhancer candidate materials. Its potential for rapid candidate materials screening is showcased based on the example of nano‐sized metal–organic frameworks (nMOFs) and direct benchmarking against gold nanoparticles (the current “gold standard”). Dose enhancement factors (DEFs) ranging between 1.4 and 1.8 are measured for Hf‐, Ti‐, TiZr‐, and Au‐based materials in 3D tissues and are overall lower than in 2D cell cultures, where DEF values exceeding 2 are found. In summary, the presented co‐cultured tumor spheroid—healthy fibroblast model with tissue‐like characteristics may serve as high‐throughput platform enabling rapid, cell line‐specific endpoint analysis for therapeutic efficacy and toxicity assessment, as well as accelerated radio‐enhancer candidate screening.

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“…• nanoMOFs outperformed corresponding equi-molar metal oxide nanoparticles in in vitro X-ray radio-enhancement [238]…”

Section: In Vitro MV Photonsmentioning

confidence: 98%

Prospects of Nanoparticle-based Radioenhancement for Radiotherapy

Gerken

Gerdes

Pruschy

et al. 2023

Preprint

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Radiotherapy is a key pillar of solid cancer treatment. Despite high level of conformal dose deposition, radiotherapy is limited due to co-irradiation of organs-at risk and subsequent normal tissue toxicities. Nanotechnology offers an attractive opportunity for increasing the efficacy and safety of cancer radiotherapy. Leveraging the freedom of design and the growing synthetic capabilities of the nanomaterial-community, a variety of engineered nanomaterials have been designed and investigated as radiosensitizers or radioenhancers. While research so far has been primarily focused on gold nanoparticles and other high atomic number materials to increase the absorption cross section of tumor tissue, recent studies are challenging the traditional concept of high-Z nanoparticle radioenhancers and highlight the importance of catalytic activity. This review provides a concise overview on the fundamental knowledge of nanoparticle radioenhancement mechanisms and their quantification. It critically discusses potential radioenhancer candidate materials and general design criteria for different radiation therapy modalities, and concludes with research priorities in order to advance the development of nanomaterials, to enhance the efficacy of radiotherapy and to increase at the same time the therapeutic window.

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Cellular fate and performance of group IV metal organic framework radioenhancers

Abstract: Metal organic framework enhanced radiation.

Cited by 9 publications

References 52 publications

Radiotherapy Enhancement by Ti3C2Tx MXenes

Radiotherapy Enhancement by Ti3C2Tx MXenes

Metal–Organic Framework Mediated Radio‐Enhancement Assessed in High‐Throughput‐Compatible 3D Tumor Spheroid Co‐Cultures

Prospects of Nanoparticle-based Radioenhancement for Radiotherapy

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