New light on temperature diagnostics
Theranostic techniques enable clinicians to diagnose and treat a condition at the same time, while they can also provide rapid feedback on the effectiveness of treatment. Researchers in the NORTH project are developing hybrid nanoparticles designed to combine temperature-based diagnostics with other functions such as drug delivery, as Professor Anna Kaczmarek explains.
The idea of diagnosing medical conditions on the basis of temperature variations is fairly well established, and a variety of techniques are currently used in medicine to monitor temperatures within the body, such as thermocouples. It is known for example that cancer cells have a slightly elevated temperature in comparison to healthy cells, yet the currently available monitoring techniques are highly invasive. “Putting a thermocouple into the human body involves very invasive techniques,” explains Anna Kaczmarek, Professor in the Department of Chemistry at Ghent University in Belgium. “The research community has been looking for improved, non-invasive ways of measuring temperature at the nanoscale, and luminescence thermometry has emerged as a potential route to achieving this.”
NORTH project
This is a topic Professor Kaczmarek is exploring as Principal Investigator of the ERC-backed NORTH project, in which she and her team are working to develop new multi-functional hybrid nanoparticles. This research centres on periodic mesoporous organosilicas (PMOs), a group of very ordered porous materials which Professor Kaczmarek says can be used in various different ways. “There are a lot of possibilities with PMOs to create materials which are biodegradeable, biocompatible, and also highly porous,” she outlines. Researchers in the project are now looking to combine these PMOs with a group of chemical elements called lanthanides, some of which are well-suited to luminescence thermometry. “They’re not affected by the environment in which they’re being used, which is beneficial for luminescence thermometry,” explains Professor Kaczmarek. The team behind the NORTH project is investigating these lanthanides with respect to their potential in luminescence thermometry, as well as in other functions. There are 15 lanthanides, many of which have luminescence properties, and researchers have identified several which are particularly interesting for biological applications. “We’ve narrowed it down and are working with a few of these lanthanides,” says Professor Kaczmarek. Researchers typically use combinations of these elements, as this approach tends to be more
Electron
sensitive than using a single lanthanide. “We work for example with combinations of holmium and ytterbium. We’re also exploring thuliumbased systems, such as thulium combined with ytterbium, or also with neodymium or erbium,” outlines Professor Kaczmarek.
A lot of thermometers are currently made using lanthanides, yet these are purely inorganic particles that can’t really be loaded with drugs or used to produce an effective photodynamic therapy (PDT) agent. This is where the PMOs come into play. “The PMO not only makes the hybrid material more biocompatible, but it also adds porosity. You can then load a PDT agent or an anti-cancer drug such as doxorubicin for example,” says Professor Kaczmarek. The project team is now looking to develop effective nanoparticles using these materials; Professor Kaczmarek says size and shape are important considerations. “Larger particles can be toxic, while we also don’t want the nanoparticles to be too small, as that causes some retention problems. Around 100 nanometres would be
ideal,” she continues. “We’re looking to develop spherical particles, as we also know that rod shapes can be toxic.”
The idea is that the particle would be activated with light once it reaches a specific location in the body, such as the site of a tumour for example. This would then allow researchers to monitor temperatures, and potentially release an anti-cancer drug. “We aim to use two wavelengths of light simultaneously, one of which could be used to activate the material to show a temperature read-out,” explains Professor Kaczmarek. A lot of progress has been made in this area over the course of the project, with Professor Kaczmarek and her colleagues demonstrating that their hybrid particles can combine thermometry and drug delivery. “We see that there’s some signal interference, which is related to the presence of spectral overlaps. But we also see that we can still use the nanoparticles as a thermometer and as a drug release agent simultaneously without any issues,” she continues.
Researchers are also investigating the possibility of combining thermometry with PDT, work which is still in its early stages. This is one of the main topics currently on the project’s agenda, alongside research into achieving ondemand drug delivery. “We don’t want a drug to be slowly released while the theranostic material is on the way to a specific site like a tumour, we want the drug to be released when it gets there. We’re still trying to optimise that and to implement PDT,” outlines Professor Kaczmarek. The ultimate aim is to use these nanoparticles to diagnose and treat human patients, yet Professor Kaczmarek says there is still much more work to do before they can be applied clinically. “There are still concerns around the biocompatibility and performance of these materials,” she acknowledges. “There is still a long road ahead before any thermometer materials reach clinics.”
Degradeability and feedback during treatment
These are issues Professor Kaczmarek plans to address in a follow up ERC- funded proof-ofconcept project called LUMITOOLS, building on the progress that has been made in NORTH. Through this project Professor Kaczmarek aims
Luminescence thermometry map of newly developed near infrared thermometers. The blue line represents 20°C, the red line 60°C. The ratio of the two peaks is used to build a calibration curve.
thermometry can also be used as a feedback tool,” continues Professor Kaczmarek. “For example, if you want to combine thermometry and photothermal therapy to treat a tumour then you need feedback.”
The cancerous tissue would need to be heated to a high temperature, but it would also be extremely important to avoid over-heating nearby tissue and causing new problems. These nanoparticles could provide rapid feedback to a clinician in these kinds of circumstances,
“The research community has been looking for improved, noninvasive ways of measuring temperature at the nanoscale, and luminescence thermometry has emerged as a potential route to achieving this.”
to overcome the main concerns around these materials, and move them closer to practical application. “How can we convince the medical community to start using these materials? This in large part comes down to degradeability,” she says. If these concerns can be addressed, then these kinds of multi-functional materials could prove extremely useful for the medical community. “There are many potential applications, and not just in diagnostics -
helping guide treatment and tailor it to the needs of individual patients. “The idea is to provide feedback during therapy,” says Professor Kaczmarek. The project team is now also working towards this objective, with researchers testing combinations and improving the nanoparticles, with the long-term goal of bringing them to practical application. “We’ve developed some very interesting materials and thermometers in the project,” continues Professor Kaczmarek.
NORTH
NanOthermometeRs for THeranostic
Project Objectives
Developing multifunctional nanoplatforms, which combine both temperature sensing (as a diagnostic tool) and the therapy of disease (drug delivery/photodynamic therapy/photothermal therapy), as proposed in the ERC Stg project NORTH, can change the way that certain diseases are treated.
Project Funding
This project is funded by the European Research Council ERC Starting Grant NanOthermometeRs for THeranostics (NORTH) under grant agreement No 945945.
Follow up project: European Research Council
ERC Proof of Concept project LUMInescence
ThermOmeters fOr cLinicS (LUMITOOLS) under grant agreement No 101137651.
Contact Details
Project Coordinator,
Prof. dr. Anna M. Kaczmarek Ghent University
Department of Chemistry
Krijgslaan 281-S3, 9000 Ghent
Belgium
T: +32 9 264 48 71
E: anna.kaczmarek@ugent.be W: https://nanosensing.ugent.be
Dr Anna M. Kaczmarek studied Chemistry at Adam Mickiewicz University in Poland and acquired a PhD at Ghent University, Belgium in the field of lanthanide materials. After several post-doctoral positions in Belgium and visits abroad she created the NanoSensing Group (Ghent University) which focuses on developing (hybrid) luminescent nanothermometers for biomedical applications. Privately she is mom to 6 month old daughter Marie.
