University of Groningen Fluorescent Nanodiamonds as Free Radical Sensors in Aging Yeast Cells van der Laan, Kiran

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Fluorescent Nanodiamonds as Free Radical Sensors in Aging Yeast Cells

van der Laan, Kiran

DOI:

10.33612/diss.112906297

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

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Publication date: 2020

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Citation for published version (APA):

van der Laan, K. (2020). Fluorescent Nanodiamonds as Free Radical Sensors in Aging Yeast Cells: a baker’s yeast response to small diamonds with great potential!. Rijksuniversiteit Groningen.

https://doi.org/10.33612/diss.112906297

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Nanodiamonds and Their Applications in Cells

Mayeul Chipaux1a_{, Kiran J. van der Laan}1a_{, Simon R. Hemelaar}a_{, Masoumeh} Hasanib_{, Tingting Zheng}c_{, Romana Schirhagl*}a

1_{These authors have contributed equally.}

a Groningen University, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AW Groningen, Netherlands, email corresponding author:

romana.schirhagl@gmail.com

b Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran

c Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Department of Ultrasound, Peking University Shenzhen Hospital & Biomedical Research Institute,

Shenzhen-PKU-HKUST Medical Center, 518036 Shenzhen, China

Small 14: 24 1704263 (2018).

Abstract

Diamonds owe their fame to a unique set of outstanding properties. They combine a high refractive index, hardness, great stability and inertness and low electrical but high thermal conductivity. Diamond defects have recently attracted a lot of attention. Given this unique list of properties, it is not surprising that diamond nanoparticles have been utilized for numerous applications. Due to their hardness they are routinely used as abrasives. Their small and uniform size qualifies them as attractive carriers for drug delivery. The stable fluorescence of diamond defects allows their use as stable single photon source or biolabel. The magnetic properties of the defects make them stable spin qubits in quantum information. This property also allows their use as a sensor for temperature, magnetic fields, electric fields or strain. This Review article focusses on applications in cells. Different diamond materials and the special requirements for the respective applications are discussed. Methods to chemically modify the surface of diamonds and the different hurdles one has to overcome when working with cells, such as entering the cells and biocompatibility, are described. Finally, the recent developments and applications in labeling, sensing, drug delivery, theranostics, antibiotics and tissue engineering are critically discussed.

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Nanodiamonds and Their Applications in Cells

Mayeul Chipaux1a_{, Kiran J. van der Laan}1a_{, Simon R. Hemelaar}a_{, Masoumeh} Hasanib_{, Tingting Zheng}c_{, Romana Schirhagl*}a

1_{These authors have contributed equally.}

a Groningen University, University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AW Groningen, Netherlands, email corresponding author:

romana.schirhagl@gmail.com

b Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, Hamedan 6517838683, Iran

c Shenzhen Key Laboratory for Drug Addiction and Medication Safety, Department of Ultrasound, Peking University Shenzhen Hospital & Biomedical Research Institute,

Shenzhen-PKU-HKUST Medical Center, 518036 Shenzhen, China

Small 14: 24 1704263 (2018).

Abstract

Diamonds owe their fame to a unique set of outstanding properties. They combine a high refractive index, hardness, great stability and inertness and low electrical but high thermal conductivity. Diamond defects have recently attracted a lot of attention. Given this unique list of properties, it is not surprising that diamond nanoparticles have been utilized for numerous applications. Due to their hardness they are routinely used as abrasives. Their small and uniform size qualifies them as attractive carriers for drug delivery. The stable fluorescence of diamond defects allows their use as stable single photon source or biolabel. The magnetic properties of the defects make them stable spin qubits in quantum information. This property also allows their use as a sensor for temperature, magnetic fields, electric fields or strain. This Review article focusses on applications in cells. Different diamond materials and the special requirements for the respective applications are discussed. Methods to chemically modify the surface of diamonds and the different hurdles one has to overcome when working with cells, such as entering the cells and biocompatibility, are described. Finally, the recent developments and applications in labeling, sensing, drug delivery, theranostics, antibiotics and tissue engineering are critically discussed.

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1. Introduction

Diamonds are arguably the most valued gemstones. Moreover, due to a unique set of properties diamonds are also highly valued for a large number of other applications. Diamond is one of the hardest materials1_{and a very good thermal} conductor,2_{while being an excellent electrical insulator.}3_{While these properties} on its own are already interesting, it is really unique that they are all combined in one material. Due to the high covalent bond strength between the carbon atoms, diamond is very inert. However, the rich surface chemistry allows to attach all kinds of molecules.4

The many stable defects in diamond offer a whole new set of possibilities. Since they are well protected inside the crystal they are uniquely stable.5_{Thus nanodiamond-based labels can be observed for long times. In} addition, some defects have become popular since they change their fluorescence based on their magnetic surrounding. This effect can be utilized in nanoscale quantum sensing.

Several different aspects of nanodiamonds and their applications have already been reviewed: magnetometry,6,7_{surface chemistry,}8,9_{the physics of} defects,10_{tracking or imaging,}11_{drug delivery}12,13_{or a combination of several} applications.14–18_{There are a few recent articles about bioapplications of} diamonds, but they do not specifically focus on cells. Turcheniuk et al. focus mainly on detonation nanodiamonds and its applications19_{, whereas Hsiao et al.} provide a shorter review where they discuss temperature sensing, super resolution imaging and tracking.20_{Here we review applications of} nanodiamonds in cells. To this end we will first discuss different diamond materials and their key properties. There are different ways of synthesizing nanodiamonds leading to diamond material with different sizes, different purities and entirely different properties. Next we discuss how diamonds can enter the cell and what we currently know about their biocompatibility. Then we will review how diamonds can be optimized for intracellular applications. Finally we will highlight different applications of nanodiamonds in cells. We will first introduce applications that rely on the optical properties of diamonds. Then we will continue with applications which make use of the small and reproducible size, with narrow size distribution.21_{These so-called detonation nanodiamonds} are useful as carriers of other substances, which are assembled around them. This concept leads, for instance, to applications in drug delivery.

2. Diamond Starting Materials

With the quick rise of interest in diamond materials and the demand of ever purer materials, new innovations in producing nanodiamonds have emerged. These materials are often mixed up in the literature and especially in older articles it was not always specified which material was used. By now there are numerous materials available in different sizes and shapes with entirely different properties. In this section the different materials that are currently available are introduced, starting from the simplest. Additionally, we will indicate for each application which diamond material is suited best in the later sections.

Historically, the first diamond nanomaterials that were utilized were detonation nanodiamonds (DNDs). These are created when selected organic compounds are brought to explosion in a controlled way.22_{DNDs are typically} round to oval in shape and measure uniformly about 5 nm in size.22_{Their small} size and narrow size distribution make them a popular research topic. If not especially cleaned however, they tend to aggregate with each other. Additionally, they are relatively chemically inert, but still reactive enough to allow functionalization. Another advantage is their large relative surface area, which can be used to effectively attach different compound. These properties of DNDs are, for instance, very advantageous in drug delivery. Due to their structural composition and creation method, DNDs usually have a graphitic layer on the outside and relatively many impurities and structural defects.23_Although stable defects have occasionally been observed in diamonds at this size24_and even down to 1.6 nm crystals,25_{this is still rather rare. Their small size thus} renders them impracticable if defined defects are needed, as in quantum sensing applications. Even more so, if a high number of defects in the diamond is desired, which is the case for labelling applications. However, there are some recent developments, which might render DNDs more useful for labelling. They can be used as support for dyes26,27_{or their surface chemistry can be tuned to} achieve desired optical properties.28

A different type of nanodiamonds is available from high pressure high temperature (HPHT) synthesis followed by grinding down the material to the desired sizes.29_{Different size fractions of this material are available with average} particle sizes between 10 nm and up to micrometer sizes. Due to their use as abrasives, these materials are produced on a large scale and thus comparably

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1. Introduction

Diamonds are arguably the most valued gemstones. Moreover, due to a unique set of properties diamonds are also highly valued for a large number of other applications. Diamond is one of the hardest materials1_{and a very good thermal} conductor,2_{while being an excellent electrical insulator.}3_{While these properties} on its own are already interesting, it is really unique that they are all combined in one material. Due to the high covalent bond strength between the carbon atoms, diamond is very inert. However, the rich surface chemistry allows to attach all kinds of molecules.4

The many stable defects in diamond offer a whole new set of possibilities. Since they are well protected inside the crystal they are uniquely stable.5_{Thus nanodiamond-based labels can be observed for long times. In} addition, some defects have become popular since they change their fluorescence based on their magnetic surrounding. This effect can be utilized in nanoscale quantum sensing.

Several different aspects of nanodiamonds and their applications have already been reviewed: magnetometry,6,7_{surface chemistry,}8,9_{the physics of} defects,10_{tracking or imaging,}11_{drug delivery}12,13_{or a combination of several} applications.14–18_{There are a few recent articles about bioapplications of} diamonds, but they do not specifically focus on cells. Turcheniuk et al. focus mainly on detonation nanodiamonds and its applications19_{, whereas Hsiao et al.} provide a shorter review where they discuss temperature sensing, super resolution imaging and tracking.20_{Here we review applications of} nanodiamonds in cells. To this end we will first discuss different diamond materials and their key properties. There are different ways of synthesizing nanodiamonds leading to diamond material with different sizes, different purities and entirely different properties. Next we discuss how diamonds can enter the cell and what we currently know about their biocompatibility. Then we will review how diamonds can be optimized for intracellular applications. Finally we will highlight different applications of nanodiamonds in cells. We will first introduce applications that rely on the optical properties of diamonds. Then we will continue with applications which make use of the small and reproducible size, with narrow size distribution.21_{These so-called detonation nanodiamonds} are useful as carriers of other substances, which are assembled around them. This concept leads, for instance, to applications in drug delivery.

2. Diamond Starting Materials

With the quick rise of interest in diamond materials and the demand of ever purer materials, new innovations in producing nanodiamonds have emerged. These materials are often mixed up in the literature and especially in older articles it was not always specified which material was used. By now there are numerous materials available in different sizes and shapes with entirely different properties. In this section the different materials that are currently available are introduced, starting from the simplest. Additionally, we will indicate for each application which diamond material is suited best in the later sections.

Historically, the first diamond nanomaterials that were utilized were detonation nanodiamonds (DNDs). These are created when selected organic compounds are brought to explosion in a controlled way.22_{DNDs are typically} round to oval in shape and measure uniformly about 5 nm in size.22_{Their small} size and narrow size distribution make them a popular research topic. If not especially cleaned however, they tend to aggregate with each other. Additionally, they are relatively chemically inert, but still reactive enough to allow functionalization. Another advantage is their large relative surface area, which can be used to effectively attach different compound. These properties of DNDs are, for instance, very advantageous in drug delivery. Due to their structural composition and creation method, DNDs usually have a graphitic layer on the outside and relatively many impurities and structural defects.23_Although stable defects have occasionally been observed in diamonds at this size24_and even down to 1.6 nm crystals,25_{this is still rather rare. Their small size thus} renders them impracticable if defined defects are needed, as in quantum sensing applications. Even more so, if a high number of defects in the diamond is desired, which is the case for labelling applications. However, there are some recent developments, which might render DNDs more useful for labelling. They can be used as support for dyes26,27_{or their surface chemistry can be tuned to} achieve desired optical properties.28

A different type of nanodiamonds is available from high pressure high temperature (HPHT) synthesis followed by grinding down the material to the desired sizes.29_{Different size fractions of this material are available with average} particle sizes between 10 nm and up to micrometer sizes. Due to their use as abrasives, these materials are produced on a large scale and thus comparably

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Processed on: 21-1-2020 PDF page: 92PDF page: 92PDF page: 92PDF page: 92 cheap. There are different approaches to obtain different sizes. Centrifuging the

smallest commercially available products and only using supernatant, for instance, leads to particle sizes down to 4 nm on average.30_{Another method to} decrease size is to use oxidation. HPHT diamonds can naturally host different defects as, for instance, nitrogen vacancy (NV) centers and are thus the simplest material that is suitable for quantum sensing applications. By now, also irradiated HPHT diamond material with an increased number of defects are commercially available, as well as diamonds with different surface chemistry. Due to their increased brightness, these materials are most suitable for optical labelling. Depending on the diamond size, one diamond nanoparticle can host up to thousands of defects.

While these HPHT diamonds usually have sharp edges and a flake-like geometry,31_{particles with round shapes have also been produced. These are} generated from sharp edged diamond particles by short-term oxidation in melted potassium nitrate.32_{For applications in cells, these are particularly} interesting, since they are ingested into cells differently than particles with sharp edges (see Figure 2a,b).33

Another approach to produce nanodiamonds starts with diamondoid structures, small molecule units with a diamond crystal structure (Figure 1c). The nanodiamond is grown around this molecule.34,35_{During the synthesis of} this molecule, foreign atoms can be placed at the desired locations. This method promises the most accurate control over the exact location of defects and might even give the opportunity to place two or more defects at a defined distance from each other. However, so far, the small yields obtained by this method have complicated characterizing the material and subsequently employing the full potential of the method.

Figure 1. Different nanodiamond materials: a) A model of a detonation nanodiamond.

pressure high temperature synthesis (scale bar: 200 nm). c) A new approach is shown which starts with a (diamondoid) seed (in this case an HPHT diamond), which is then overgrown by a pure chemical vapor deposition (CVD) diamond. Reproduced with permission.22,36,37_{Copyright 2012, Springer Nature, Copyright 2014, ACS Publications,}

and Copyright 2015, Wiley-VCH. d) A sequence of synthesis steps that lead to nanofabricated diamonds. (1) First, metal particles are deposited onto the diamond surface. (2) Then, the diamond is etched while the particles protect the area beneath. (3) After removing the metal, (4) defects are implanted. (5) Finally, the particles are broken off from the surface and ready to use.

The increased demand on diamond purity, mainly for quantum sensing application, and the desired control over the defect architecture have led to the development of two more innovations. An innovative approach is to start from bulk diamond materials and then produce nanodiamonds by nanofabrication, as illustrated in Figure 1d.36_{This has the striking advantage that bulk diamonds can} be created in very high purity. Implanting them from the surface also gives a good control over the positioning of the defect.38_{Moreover, with this approach,} the shape of the particle can be controlled in the fabrication process. While this method has produced nanodiamonds with the best purity and thus is most promising for quantum sensing, it is obviously more complicated, expensive and time consuming than the above-mentioned approaches.

Apart from the already mentioned techniques, a few others have been developed. However, these have not received such widespread attention since they are produced in low yields and/or low quality of the material. Examples are irradiation of graphite or carbon onions,39,40_{laser ablation}41_{or the use of} ultrasound.42

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Processed on: 21-1-2020 PDF page: 93PDF page: 93PDF page: 93PDF page: 93 cheap. There are different approaches to obtain different sizes. Centrifuging the