KANAZAWA, Japan, July 4, 2022 /PRNewswire/ — Researchers from Kanazawa University report in ACS Nano the development of a nanoparticle that acts as a heating element and a thermometer. The insertion of the nanoparticle into living cells creates a heat point which, by switching it on and off, allows the controlled modulation of local cellular activities.
Being able to heat nanoscale regions in biological tissues is key to several biomedical applications. Indeed, many biological processes are temperature sensitive, and the ability to locally alter temperature provides a means to manipulate cellular activity. A notable goal is the destruction of cancer cells by heating them. In addition to the need for a local heating mechanism in the tissues, it is also important to be able to instantly measure the temperature generated. Satoshi Arai from Kanazawa University and his colleagues have now designed a nanoparticle that is both a nanoheater and a nanothermometer. They have successfully shown that inserting a single point of controllable heat into tissues can be very effective in altering cell function.
The nanoparticle, called “nanoHT” by scientists – short for “nanoheater-thermometer” – is essentially a polymer matrix incorporating a dye molecule (called EuDT) used to sense temperature, and another dye molecule (called V- Nc) to release Heat. The latter occurs through the conversion of light into thermal energy (the photothermal effect, also exploited in solar cells): shining a near-infrared laser (with a wavelength of 808 nanometers) on V-Nc results in a rapid heating, with greater temperature rise for higher laser power.
Temperature sensing is based on the thermal fluorescence effect of EuDT. When irradiated with light of one wavelength, the molecule emits light at another wavelength – fluorescence. The higher the temperature, the less intense the fluorescence becomes. This inverse relationship can be used to measure temperature. Arai and his colleagues tested the performance of the nanoHT as a thermometer and found that it can determine temperatures with a resolution of 0.8°C and less.
The researchers then performed experiments with a type of human cell called HeLa cells. They examined the effect of nanoHT heating and found that at a temperature increase of about 11.4°C, heated HeLa cells died after only a few seconds. This finding suggests that nanoHT could be used to induce cell death in cancer cells.
Arai and his colleagues also investigated how nanoHT can be used to affect muscle behavior. They introduced the nanoparticle into the myotube, a type of fiber found in muscle tissue. Upon heating the myotube by approximately 10.5°C, the muscle tissue contracted. The procedure worked reversibly; allowing the myotube to cool again resulted in muscle relaxation.
Work by Arai and colleagues shows that local heating at a subcellular scale using nanoHT enables the controlled manipulation of single cell activity. Regarding applications, the scientists believe that “targeted application of nanoHT has a diverse and versatile range of abilities to regulate cellular activities that would facilitate the development of thermodynamic cellular engineering.”
Fluorescence refers to the emission of light by a substance after which it has absorbed light (or another type of electromagnetic radiation). Typically, the emitted light has a longer wavelength, and therefore lower photon energy, than the absorbed radiation. A well-known case of fluorescence occurs when the absorbed radiation is in the ultraviolet region of the spectrum, invisible to the human eye, while the emitted light is in the visible region.
Fluorescent thermometry is a technique for measuring temperatures through the use of fluorescent dye molecules, the fluorescence intensity of which is strongly dependent on temperature. Dye molecules are inserted into a material of interest; a detailed knowledge of the fluorescence intensity as a function of temperature dependence allows the temperature of the material to be inferred. (Dye molecules are excited to fluoresce by incident light; its intensity provides a measure of local temperature.)
Satoshi Arai from Kanazawa University and his colleagues used fluorescent dye molecules to develop nanoHT, a nanoparticle that acts as both a heater and a thermometer for nano-bio applications.
Ferdinand, madoka suzukiCong Quang Vu, Yoshie Harada, Satya Ranjan SarkerShinichi Ishiwata, Tetsuya Kitaguchiand Satoshi Arai. Modulation of local cellular activities using a photothermal dye-based subcellular-sized heat spot, ACS Nano 169004–9018 (2022).
Figure 1. Thermodynamic cellular engineering: creating a tiny point of heat helps regulate cellular functions
Figure 2. Microscopic system for nanoheating. A) Schematic and microscopic images of nanoheater (nanoHT) (transmission electron microscopy). B) A system for warming a localized region at the single cellular level (upper panel). A single nanoHT dot was located in a single cell (lower left panel). The microscale temperature gradient was generated at the subcellular level (lower right panel).
Figure 3. A nanoparticle combining photothermal heating and fluorescence thermometry functions as a localized heat point and is able to induce cell death or muscle contraction.
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WPI Nano Life Sciences Institute (WPI-NanoLSI)
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About the Nano Life Science Institute (WPI-NanoLSI)
The Nano Life Science Institute (NanoLSI) at Kanazawa University is a research center established in 2017 under the World Premier International Research Center Initiative of the Ministry of Education, Culture, Sports, Science and Technology. The objective of this initiative is to create world-class research centres. NanoLSI combines the most advanced knowledge of biological probe microscopy to establish “nano-endoscopic techniques” to directly image, analyze and manipulate biomolecules to better understand the mechanisms governing life phenomena such as diseases.
About Kanazawa University
As the leading comprehensive university in the sea of Japan coast, Kanazawa University has contributed greatly to higher education and academic research in Japan since its inception in 1949. The University has three colleges and 17 schools offering courses in subjects including medicine, computer engineering, and humanities.
The University is located on the sea coast of Japan in Kanazawa – a city rich in history and culture. The city of Kanazawa has had a highly respected intellectual profile since the time of the feud (1598-1867). The University of Kanazawa is divided into two main campuses: Kakuma and Takaramachi for its approximately 10,200 students, including 600 foreigners.
SOURCE Kanazawa University