Developing Light- Responsive Drug Carriers and Diagnostic Sensors Dr Xiaoqiang Chen DEVELOPING LIGHT- RESPONSIVE DRUG CARRIERS AND DIAGNOSTIC SENSORS Delivering drugs to their target site and conducting medical diagnostics non-invasively are two major goals of biomedical researchers across the globe. Dr Xiaoqiang Chen and his team of scientists at Nanjing Tech University in China are developing advanced materials and procedures that can keep drugs protected before they reach their target site in the body. The group is also developing materials that can be used to detect certain substances in the body, towards providing non-invasive diagnostic tools for clinicians. Drug Delivery and Diagnostics in a more controlled manner at its intended site. At the same time, the Developing new ways of administering team is also developing biological drugs to where they are required in sensors that can monitor cell activity in the body is a challenging pursuit. For a non-invasive manner. instance, drug molecules not only need to reach their target site, but must also Central to Dr Chen’s research is the be protected in order to survive the study of how light interacts with body’s natural defences along the way. molecules. In his drug delivery research, The search for new materials that can he employs UV as an energy source to transport drugs safely to their target is break molecular bonds, allowing drug Dr Chen’s team investigated how current thus an active field of research. molecules to be released on cue. In light-based sensors, some of which his team’s diagnostic research, they have limited detection ranges, could Similarly, countless researchers are also utilise excited light to cause biological be improved. The team investigated attempting to develop non-invasive molecules to emit visible light signals – how a class of molecules called medical sensors for a range of different or ‘fluorescence’. Such fluorescence can ‘benzothiazoles’, which can bind to zinc applications. For example, a sensor that be recorded accurately with an external ions, responds after irradiation with UV could non-invasively measure levels sensor, providing key information about light. They found that in the absence of the neurotransmitter acetylcholine the levels of the molecule of interest. of zinc, the benzothiazole molecules would allow clinicians to easily emitted a yellow fluorescence, but identify and monitor the development Molecules that Glow when bound to zinc, they emitted a blue Alzheimer’s disease, allowing for timely signal. Importantly, the researchers were diagnosis, and offering a simple way of Zinc ions are vital to the survival of all able to view these colour signals from measuring treatment effectiveness. living organisms. In humans and other outside cells, allowing for non-invasive animals, zinc is involved in immune monitoring. Dr Xiaoqiang Chen and his team at system and brain functions. Therefore, Nanjing Tech University are making finding reliable ways of detecting and After these experiments, Dr Chen’s team substantial leads in both areas of replenishing zinc levels at the cellular then realised that the concentration of research. They are designing ‘prodrugs’ level is of great significance. zinc ions was related to the intensity that release the active drug molecule of the fluorescence signal. Their new WWW.SCIENTIA.GLOBAL detection system allows them to subjected to prolonged UV exposure in The above-mentioned research was determine the concentration of zinc order to release the zinc, which can be performed outside of cells, so the by simply analysing the colour of the dangerous. team was keen to demonstrate the sample. Furthermore, the team was release of zinc inside cells. To do this, able to detect concentrations as low Dr Chen’s photocage is based on a they incubated cells with caged zinc as approximately one ten-billionth of a derivative of a chemical known as ions at 37°C. Upon irradiating with UV gram of zinc per litre of solvent. Sanger’s reagent, which opens much irradiation, the cages released their more easily when irradiated with UV. zinc ions. Fortunately, the caged zinc Releasing Drugs from Their Cage His team was also able to identify the compounds showed little to no toxicity breakdown products resulting from the before and after UV irradiation. Following these studies, Dr Chen and decomposition of the photocage, which his colleagues then set about designing is an important requirement in the After this success, Dr Chen proceeded to drug candidates that could potentially development of new drugs. investigate a molecule that slows down replenish zinc levels. To do this, the an enzyme called acetylcholinesterase. team designed what they refer to as In order to demonstrate the effective Acetylcholinesterase is located in ‘photocages’, which can carry zinc release of zinc in a more realistic the gaps between nerve cells and ions or other therapeutic substances. situation, Dr Chen’s team tested the muscle cells, which breaks down When irradiated with UV light, these photocaged zinc against an enzyme the neurotransmitter acetylcholine photocages open and release their which has an activity that is accelerated after it transmits a signal, thereby contents. Such cages can protect the by high levels of zinc ions. They found stopping the signal. The introduction zinc ions from the surroundings as they that as the irradiation time increased, of an ‘inhibitor’ molecule, which slows travel to the target site, where they can the activity of the enzyme increased, down acetylcholinesterase, would be irradiated with a beam of UV beam. indicating that zinc was being released. subsequently prevent the breakdown of The researchers were also able to acetylcholine, thus maintaining signal There are several known photocages control how much the enzyme was transmission. that can carry zinc to a target site in activated by precisely controlling the UV cells. However, these compounds parameters. When tested out on heart cells, which require high levels of UV exposure before pulse upon signal transmission, the they will open, ultimately meaning that team found that their photocage experimental samples would need to be efficiently protected the inhibitor of WWW.SCIENTIA.GLOBAL acetylcholinesterase. Using UV irradiation to interact with the Dr Chen and his team studied a class of molecules, known caged inhibitor, they were able to control when the pulse of the as ‘spiropyrans’, which can reversibly change between two cells returned. This shows that the inhibitor was released from different chemical states. Like photocages, when UV light its cage and was able to block the action acetylcholinesterase is shone on a spiropyran molecule, some of the bonds enzyme. break, leading to a change in its chemical structure. This new ‘isomerisation structure’ is temporary and causes the Furthermore, the researchers found that neither UV light nor the spiropyran to appear green. Dr Chen’s team demonstrated how caged inhibitor alone influenced the pulse rate, demonstrating the green form of spiropyran then reverts back to its original, that both were needed to elicit a response. ‘These successful colourless state. Knowing this, the team then conducted an proof-of concept examples open a new avenue for using extensive study showing the behaviours of the surface of a Sanger’s reagent-based photolabile compounds in the solvent containing spiropyran as it evaporates. When the exploration of the complex cellular functions and signalling solvent evaporates, the molecules at the surface aggregate pathways,’ says Dr Chen. spontaneously due to the surface tension. Molecular-Assisted Imagery Prior to evaporation, the spiropyran molecules were distributed randomly in the test solvent. The team found that irradiation In dissipative structure theory, once some parameters of an with UV resulted in a uniformly spread green colour, with no open system reach a certain threshold far from the equilibrium discernible pattern. When evaporation had occurred and state, mutations will take place in the system by increasing and the temperature was in a suitable range, the researchers decreasing, from non-order to order. In this research area, Dr observed an ordered temperature distribution on the surface Chen’s team apply their knowledge of light-sensitive materials of the evaporating solvent. The spiropyran molecules then to trace dissipative structures during the evaporation of organic congregated in the colder area and were no longer randomly solvent. This work also helps other research groups to build distributed, instead forming an ordered and green coloured efficient methods to observe thermal field distributions and pattern when the solvent was subjected to UV light. Dr Chen’s flow patterns on the surface of fluids. In addition to designing findings also agreed with infrared images taken at the same methods, the team’s research is also helpful in understanding time but, as intended, his technique achieved a much higher the fundamental mechanism involved in other industrial resolution. processes, including the growth of crystals, droplet evaporation and microfluidics. In their study, Dr Chen’s team used photo-stimulated spiropyran as a tool to observe the temperature distribution Understanding how temperature induces fluid motion and and flow pattern on the surface of fluids; however, they now vice versa is important in several fields. However, it is quite hope that their results can be applied to other contexts where difficult to precisely map the temperature distribution