Theranostics and Image Guided Drug Delivery
Preface
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Published:02 Jan 2018
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Special Collection: 2018 ebook collectionSeries: Drug Discovery
Theranostics and Image Guided Drug Delivery, ed. M. Thanou, The Royal Society of Chemistry, 2018, pp. P007-P010.
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Future and emerging technologies in drug therapy may include a certain element of imaging. The recent advances in imaging have opened the route for the development of a new type of non-invasive treatment named interventional radiology. Interventional Radiology includes a range of therapies which rely on the use of image guidance, such as fluoroscopy, ultrasound, or magnetic resonance imaging (MRI) to precisely target treatments. Most of these techniques are minimally invasive or non-invasive treatments. Usually termed as image guided surgery these techniques combine imaging with radiofrequency ablation, electromagnetic radiation, microwaves, light, and/or high intensity focused ultrasound for the focal modulation of the temperature of the target (hyperthermia and/or ablation) with the aim to remove lesions and unhealthy tissues. Image guided drug delivery is a much-related novel concept and another emerging field that aims to optimise drug targeting using information provided by real-time medical imaging of the drug and or its carrier. Image guided drug delivery can be used to monitor biodistribution, as well as drug carrier behaviour such as drug release. In the clinic, image guided drug delivery can be used to substantially improve pharmacokinetics, and therefore the safety and the therapeutic potential of the drug treatment. If the drugs can be imaged while they are in the body, then it is easy to control their pharmacokinetics and tissue distribution. Similar to image guided surgery, image guided drug delivery combines imaging and drug therapy. Image guided drug delivery employs either sound, light or electro-magnetic energy to change the state of the drug molecules and activate them in order to activate their pharmacological action only where it is required in the body. This provides an excellent method for targeted drug delivery and therapy. For diseases such as cancer this becomes important as it is now possible to direct potent cytotoxic drugs to act only in tumours. For this type of therapy researchers are seeking the development of methods that do not use ionising radiation for imaging. Furthermore, it is important to use radiation sources that can be focused in a small defined volume in the tissue. Theranostics are compounds that are used to diagnose and treat diseases. Theranostics is a term derived from the words diagnosis and therapy and was coined to define efforts in clinics to develop specific, individualized therapies, and to combine diagnostic and therapeutic capabilities into a single agent. Theranostics may be one molecule that carries the probe for imaging coupled onto the therapeutic agent (e.g. radiolabelled antibodies) or a nanoparticle that is composed of the carrier the imaging probe or material and the therapeutic. Emphasis has been given to nanosized theranostics due to their potential in cancer treatments. Theranostics play a significant role in the development of image guided drug delivery treatments.
The scope of the book is to introduce the topic of image guided drug delivery to the scientific community and highlight its interdisciplinary approach, its efficiency and its translational ability. As such the book covers all recent and novel research efforts that address issues of theranostics and image guided drug delivery. Emphasis has been given to therapeutic concepts that reached clinical trials. Some of these methods are likely to emerge as disruptive technologies in healthcare.
The book begins by presenting advances in MRI guided focused ultrasound methods and its application in drug delivery. Focused ultrasound mediated drug delivery has been applied in several studies with various drug molecules to improve their local distribution in diseased tissues. In this case an imaging modality such as MRI or ultrasound is used to assess the method and to provide evidence of drug release. The increased temperature induced by focused ultrasound (hyperthermia) can improve blood supply in tissues and therefore improve drug distribution.
Multifunctional nanoagents that combine diagnostic and therapeutic functions for antitumor treatments and respond to near infra-red light are presented. In particular, combining real-time imaging with spatially precise photothermal therapy mediated by nanoparticles responsive to near-infrared (NIR, λ = 700–1100 nm) light through conversion of photo energy into heat. This therapeutic strategy is characterised by its simplicity, safety, and non-invasiveness, as well as targeting and remote-control release properties.
The book also describes the magnetic nanoparticles that have found application in the clinic, not only as imaging agents, but as a potent tool for treating tumours. These magnetic nanoparticles have been utilised as imaging probes for several years. When incorporated with therapeutic agents, they are specially designed to concentrate at the target site with the aid of magnetic force, resulting in theranostic function (therapy and diagnosis). MRI of magnetic nanoparticles is the most studied imaging application and has been used in the clinic with high resolution. Furthermore, their use in combination with magnetic field can provide magnetic hyperthermia that can treat tumours specifically, a concept currently being tested in clinical trials.
The emerging technique of photodynamic therapy is presented and described. Photodynamic therapy is a clinical technique for the treatment of cancers, microbial infections and other medical conditions by means of light-induced generation of reactive oxygen species using photosensitising drugs. The intrinsic fluorescence of many such drugs make them potential theranostic agents for simultaneous diagnosis and therapy. The design and development of these photosensitizers and their carriers will play an important role in designing new photodynamic treatments.
The book also introduces methods of making theranostic nanomedicines for positron emission tomography (PET) imaging. The high sensitivity and spatio-temporal resolution of PET makes this non-invasive imaging technique ideal for the in vivo tracking of liposomal nanomedicines in the clinical setting. This image guided therapeutic approach may eventually allow clinicians to select patients that would benefit from the nanomedicinal treatment and, by doing so, enhance the clinical value/efficacy of this promising treatment. This is a simple approach that can be used for personalised medicine and efficient treatments.
A special chapter is dedicated to the description and preparation of thermosensitive liposomes, a tool that is widely used in image guided drug delivery. The use of thermosensitive liposomes for anticancer treatment, which was first described in the seventies, has gained an increasing amount of attention over recent years. Various thermosensitive liposome formulations have been designed and tested in many different ways, all having various advantages and disadvantages. The composition and methods of preparation and characterisation are presented in this section.
Within the topic of formulation the book also presents recent advances on combining pharmaceutical carriers such as cyclodextrins and image guided focused ultrasound for the targeted release of chemotherapeutics. Ultrasound-mediated therapeutic drug delivery is one of various methods for local drug release and it can also influence cell permeability. Furthermore, combining it with MRI provides a controllable system for drug release and impact assessment. The chapter describes the design and development of carriers for ultrasound activated drug delivery.
For the first time the concept of image guided drug delivery in the gastrointestinal tract is presented. Special devices that can be ingested can provide energy in a controlled and focused manner to effect the tissue. These ingestible devices could promote drug therapies. Imaging and drug activation/delivery mechanism can be combined in a miniaturised piece of equipment that can be used in a way similar to capsule endoscopy. This capsule aims to apply drug therapy as well. This may be the only approach where image guidance and drug delivery are designed to act in the gut.
The last chapter provides the novel tool of microwaves and describes their potential as a cost-effective equipment for the development of imaging sensing and image guided drug delivery. It is interesting to see that early studies indicate that microwave energy interacts with nanoparticles that can affect the dielectric properties of the biological tissue. It is expected that the theranostic nanoparticles for this technology may be different compared to the ones mentioned above used by other techniques.
Overall, this book aims to present the most advanced concepts designed and currently tested in image guided drug delivery. There are concepts that are more studied than others and are now in clinical trials, such as thermosensitive liposomes and magnetic nanoparticles. There are however novel concepts such as photothermal and microwave therapy that are still at very early stage. For these the optimal chemical formulations have yet to be developed and delivered.
Although the concept of image guided drug delivery is a very recent one there are hundreds of studies presented and several strategies have moved rapidly to clinical trials to tackle unmet clinical needs. Image guided drug delivery methods hold promise to provide revolutionised methods of treating diseases.
Maya Thanou