The Latest Look at PDT and Immune Checkpoints.

Photodynamic therapy (PDT) can not only directly eliminate cancer cells, but can also stimulate antitumor immune responses. It also affects the expression of immune checkpoints. The purpose of this review is to collect, analyze, and summarize recent news about PDT and immune checkpoints, along with their inhibitors, and to identify future research directions that may enhance the effectiveness of this approach. A search for research articles published between January 2023 and March 2024 was conducted in PubMed/MEDLINE. Eligibility criteria were as follows: (1) papers describing PDT and immune checkpoints, (2) only original research papers, (3) only papers describing new reports in the field of PDT and immune checkpoints, and (4) both in vitro and in vivo papers. Exclusion criteria included (1) papers written in a language other than Polish or English, (2) review papers, and (3) papers published before January 2023. 24 papers describing new data on PDT and immune checkpoints have been published since January 2023. These included information on the effects of PDT on immune checkpoints, and attempts to associate PDT with ICI and with other molecules to modulate immune checkpoints, improve the immunosuppressive environment of the tumor, and resolve PDT-related problems. They also focused on the development of new nanoparticles that can improve the delivery of photosensitizers and drugs selectively to the tumor. The effect of PDT on the level of immune checkpoints and the associated activity of the immune system has not been fully elucidated further, and reports in this area are divergent, indicating the complexity of the interaction between PDT and the immune system. PDT-based strategies have been shown to have a beneficial effect on the delivery of ICI to the tumor. The utility of PDT in enhancing the induction of the antitumor response by participating in the triggering of immunogenic cell death, the exposure of tumor antigens, and the release of various alarm signals that together promote the activation of dendritic cells and other components of the immune system has also been demonstrated, with the result that PDT can enhance the antitumor immune response induced by ICI therapy. PDT also enables multifaceted regulation of the tumor's immunosuppressive environment, as a result of which ICI therapy has the potential to achieve better antitumor efficacy. The current review has presented evidence of PDT's ability to modulate the level of immune checkpoints and the effectiveness of the association of PDT with ICIs and other molecules in inducing an effective immune response against cancer cells. However, these studies are at an early stage and many more observations need to be made to confirm their efficacy. The new research directions indicated may contribute to the development of further strategies.

Advances in Medicine: Photodynamic Therapy.

Over the past decades, medicine has made enormous progress, revolutionized by modern technologies and innovative therapeutic approaches. One of the most exciting branches of these developments is photodynamic therapy (PDT). Using a combination of light of a specific wavelength and specially designed photosensitizing substances, PDT offers new perspectives in the fight against cancer, bacterial infections, and other diseases that are resistant to traditional treatment methods. In today's world, where there is a growing problem of drug resistance, the search for alternative therapies is becoming more and more urgent. Imagine that we could destroy cancer cells or bacteria using light, without the need to use strong chemicals or antibiotics. This is what PDT promises. By activating photosensitizers using appropriately adjusted light, this therapy can induce the death of cancer or bacterial cells while minimizing damage to surrounding healthy tissues. In this work, we will explore this fascinating method, discovering its mechanisms of action, clinical applications, and development prospects. We will also analyze the latest research and patient testimonies to understand the potential of PDT for the future of medicine.

Application of Photodynamic Therapy in Cardiology.

The origins of photodynamic therapy (PDT) date back to 1904. Since then, the amount of research proving PDT and, consequently, its applicability to various disease states has steadily increased. Currently, PDT is mainly used in oncology to destroy cancer cells. It is being worked on for possible use in other medical fields as well, including cardiology. It can be used in the prevention of restenosis, often occurring after vascular surgical interventions, for destroying atherosclerotic plaques and as a new ablative method of ectopic centers in the treatment of atrial fibrillation. The purpose of this review is to summarize the knowledge to date regarding the therapeutic potential of using PDT for various pathological conditions in cardiology. The review also focuses on the current limitations associated with the use of PDT and identifies areas where more research is needed to develop better drug regimens. Materials and methods: The study analyzed 189 medical articles. The articles came from PubMed, Frontiers, Google Scholar, Science Direct and Web of Science databases. Through the excitation of light, a photosensitizer (PS) introduced into the body, the destruction of pathological cells occurs. PTD is widely used in oncology of the central nervous system (CNS). This process is made possible by the production of free oxygen radicals (ROS) and singlet oxygen, which generate oxidative stress that destroys sensitive cancer cells. In recent years, photosensitizers have also been discovered to have a strong affinity for macrophages that fill atherosclerotic plaques, making these compounds suitable for treating atherosclerosis. By inducing apoptosis of smooth muscle cells, inactivating basic fibroblast growth factor (FGF-ß) and inhibiting endothelial cell hyperplasia, PDT can be used to prevent restenosis after surgical proceduresPDT appears to be a minimally invasive and highly effective therapeutic method, especially when combined with other therapeutic methods. Unfortunately, the small number of animal model studies and human clinical trials greatly limit the applicability of PDT on a wider scale. Current limitations, such as the depth of penetration, delivery of photosensitizer particles to the direct site of the lesion or the appropriate choice of photosensitizer in relation to the nature of the pathology, unfortunately make it impossible to replace current therapeutic approaches.

Photodynamic Therapy for Atherosclerosis.

Atherosclerosis, which currently contributes to 31% of deaths globally, is of critical cardiovascular concern. Current diagnostic tools and biomarkers are limited, emphasizing the need for early detection. Lifestyle modifications and medications form the basis of treatment, and emerging therapies such as photodynamic therapy are being developed. Photodynamic therapy involves a photosensitizer selectively targeting components of atherosclerotic plaques. When activated by specific light wavelengths, it induces localized oxidative stress aiming to stabilize plaques and reduce inflammation. The key advantage lies in its selective targeting, sparing healthy tissues. While preclinical studies are encouraging, ongoing research and clinical trials are crucial for optimizing protocols and ensuring long-term safety and efficacy. The potential combination with other therapies makes photodynamic therapy a versatile and promising avenue for addressing atherosclerosis and associated cardiovascular disease. The investigations underscore the possibility of utilizing photodynamic therapy as a valuable treatment choice for atherosclerosis. As advancements in research continue, photodynamic therapy might become more seamlessly incorporated into clinical approaches for managing atherosclerosis, providing a blend of efficacy and limited invasiveness.

Photodynamic Therapy and Cardiovascular Diseases.

Cardiovascular diseases are the third most common cause of death in the world. The most common are heart attacks and stroke. Cardiovascular diseases are a global problem monitored by many centers, including the World Health Organization (WHO). Atherosclerosis is one aspect that significantly influences the development and management of cardiovascular diseases. Photodynamic therapy (PDT) is one of the therapeutic methods used for various types of inflammatory, cancerous and non-cancer diseases. Currently, it is not practiced very often in the field of cardiology. It is most often practiced and tested experimentally under in vitro experimental conditions. In clinical practice, the use of PDT is still rare. The aim of this review was to characterize the effectiveness of PDT in the treatment of cardiovascular diseases. Additionally, the most frequently used photosensitizers in cardiology are summarized.

In Vitro MRS of Cells Treated with Trastuzumab at 1.5 Tesla.

The aim of the study was to investigate the effect of Trastuzumab on the MCF-7 and CRL-2314 breast cancer cell lines. Additionally, an attempt was made to optimize magnetic resonance spectroscopy (MRS) for cell culture studies, with particular emphasis on the impact of treatment with Trastuzumab. The research materials included MCF-7 and CRL-2314 breast cancer cell lines. The study examined the response of these cell lines to treatment with Trastuzumab. The clinical magnetic resonance imaging (MRI) system, OPTIMA MR360 manufactured by GEMS, with a magnetic field induction of 1.5 T, was used. Due to the nature of the tested objects, their size and shape, it was necessary to design and manufacture additional receiving coils. They were used to image the tested cell cultures and record the spectroscopic signal. The spectra obtained by MRS were confirmed by NMR using a 300 MHz NMR Fourier 300 with the TopSpin 3.1 system from Bruker. The designed receiving coils allowed for conducting experiments with the cell lines in a satisfactory manner. These tests would not be possible using factory-delivered coils due to their parameters and the size of the test objects, whose volume did not exceed 1 mL. MRS studies revealed an increase in the metabolite at 1.9 ppm, which indicates the induction of histone acetylation. Changes in histone acetylation play a very important role in both cell development and differentiation processes. The use of Trastuzumab therapy in breast cancer cells increases the levels of acetylated histones. MRS studies and spectra obtained from the 300 MHz NMR system are consistent with the specificity inherent in both systems.

Utility of 1.5 Tesla MRI Scanner in the Management of Small Sample Sizes Driven from 3D Breast Cell Culture.

The aim of this work was to use and optimize a 1.5 Tesla magnetic resonance imaging (MRI) system for three-dimensional (3D) images of small samples obtained from breast cell cultures in vitro. The basis of this study was to design MRI equipment to enable imaging of MCF-7 breast cancer cell cultures (about 1 million cells) in 1.5 and 2 mL glass tubes and/or bioreactors with an external diameter of less than 20 mm. Additionally, the development of software to calculate longitudinal and transverse relaxation times is described. Imaging tests were performed using a clinical MRI scanner OPTIMA 360 manufactured by GEMS. Due to the size of the tested objects, it was necessary to design additional receiving circuits allowing for the study of MCF-7 cell cultures placed in glass bioreactors. The examined sample's volume did not exceed 2.0 mL nor did the number of cells exceed 1 million. This work also included a modification of the sequence to allow for the analysis of T1 and T2 relaxation times. The analysis was performed using the MATLAB package (produced by MathWorks). The created application is based on medical MR images saved in the DICOM3.0 standard which ensures that the data analyzed are reliable and unchangeable in an unintentional manner that could affect the measurement results. The possibility of using 1.5 T MRI systems for cell culture research providing quantitative information from in vitro studies was realized. The scanning resolution for FOV = 5 cm and the matrix was achieved at a level of resolution of less than 0.1 mm/pixel. Receiving elements were built allowing for the acquisition of data for MRI image reconstruction confirmed by images of a phantom with a known structure and geometry. Magnetic resonance sequences were modified for the saturation recovery (SR) method, the purpose of which was to determine relaxation times. An application in MATLAB was developed that allows for the analysis of T1 and T2 relaxation times. The relaxation times of cell cultures were determined over a 6-week period. In the first week, the T1 time value was 1100 ± 40 ms, which decreased to 673 ± 59 ms by the sixth week. For T2, the results were 171 ± 10 ms and 128 ± 12 ms, respectively.

PDT-Induced Activation Enhanced by Hormone Response to Treatment.

Photodynamic therapy (PDT) is a medical treatment with the use of a photosensitizing agent (PS), which, when activated by light, results in selective tissue damage with a cytotoxic effect on tumor cells. PDT leads to the induction of an acute-phase response, which results in the involvement of adrenal glucocorticoid (GC) hormones. PDT, by activating the hormonal response, affects the treatment of cancer. GC release is observed due to adrenal activity, which is driven by changes in the hypothalamic pituitary-adrenal axis triggered by stress signals emanating from the PDT treated tumor. The hormones released in this process in the context of the PDT-induced acute-phase response perform many important functions during anticancer therapy. They lead, among other things, to the systemic mobilization of neutrophils and the production of acute-phase reagents, and also control the production of immunoregulatory proteins and proteins that modulate inflammation. GCs can radically affect the activity of various inflammatory and immune cells, including the apoptosis of cancer cells. A better understanding of the modulation of GC activity could improve the outcomes of cancer patients treated with PDT.

The Use of Photodynamic Therapy for Head, Neck, and Brain Diseases.

Head-neck cancers as a group have the 7th highest rate of incidence worldwide. The most often diagnosed disease of the head and neck is squamous cell carcinoma (90% of cases). Another specific group of tumors is brain tumors. These can be divided into primary tumors and secondary tumors associated with metastasis. Research shows that treating head and neck cancers continues to be problematic and challenging, and researchers are actively seeking new treatments that would improve survival rates and reduce side effects. Irradiation of tumor tissue with the optimal wavelength of light in photodynamic therapy (PDT) generates predominantly singlet oxygen in tissue-based photosensitizers (PSs) or reactive oxygen radicals in the case of vascular PSs leading to cellular apoptosis and necrosis. A very important feature of PDT is that cells cannot become immune to the effects of singlet oxygen or reactive oxygen radicals. However, photosensitizer (PS) transport is influenced by the specific structures of cancer tumors and the concentration of PS decreases in cells far from the vessel lumen. Therefore, PSs may not reach tumor interiors, which decreases therapy effectiveness. The use of drug carriers and 3rd generation PSs that contain biocompatible functional groups makes it possible to control transport. This review of the current literature on PDT was conducted through databases such as PubMed and Scopus. The types of publications considered included clinical studies and most of the articles included were published in English. Based on the publications collected, we conclude that researchers have demonstrated the potential of PDT as a therapeutic platform for head, neck, and brain diseases.

Neural Network in the Analysis of the MR Signal as an Image Segmentation Tool for the Determination of T1 and T2 Relaxation Times with Application to Cancer Cell Culture.

Artificial intelligence has been entering medical research. Today, manufacturers of diagnostic instruments are including algorithms based on neural networks. Neural networks are quickly entering all branches of medical research and beyond. Analyzing the PubMed database from the last 5 years (2017 to 2021), we see that the number of responses to the query "neural network in medicine" exceeds 10,500 papers. Deep learning algorithms are of particular importance in oncology. This paper presents the use of neural networks to analyze the magnetic resonance imaging (MRI) images used to determine MRI relaxometry of the samples. Relaxometry is becoming an increasingly common tool in diagnostics. The aim of this work was to optimize the processing time of DICOM images by using a neural network implemented in the MATLAB package by The MathWorks with the patternnet function. The application of a neural network helps to eliminate spaces in which there are no objects with characteristics matching the phenomenon of longitudinal or transverse MRI relaxation. The result of this work is the elimination of aerated spaces in MRI images. The whole algorithm was implemented as an application in the MATLAB package.

Cellular 1H MR Relaxation Times in Healthy and Cancer Three-Dimensional (3D) Breast Cell Culture.

Noninvasive measurements of 1H Magnetic Resonance Imaging (MR) relaxation times in a three-dimensional (3D) cell culture construct are presented. Trastuzumab was used as a pharmacological component delivered to the cells in vitro. The purpose of this study was to evaluate the Trastuzumab delivery by relaxation times in 3D cell cultures. The bioreactor has been designed and used for 3D cell cultures. Four bioreactors were prepared, two with normal cells and two with breast cancer cells. The relaxation times of HTB-125 and CRL 2314 cell cultures were determined. An immunohistochemistry (IHC) test was performed before MRI measurements to confirm the amount of HER2 protein in the CRL-2314 cancer cells. The results showed that the relaxation time of CRL2314 cells is lower than normal HTB-125 cells in both cases, before and after treatment. An analysis of the results showed that 3D culture studies have potential in evaluating treatment efficacy using relaxation times measurements with a field of 1.5 Tesla. The use 1H MRI relaxation times allows for the visualization of cell viability in response to treatment.

Cellular Mechanisms of Singlet Oxygen in Photodynamic Therapy.

In this review, we delve into the realm of photodynamic therapy (PDT), an established method for combating cancer. The foundation of PDT lies in the activation of a photosensitizing agent using specific wavelengths of light, resulting in the generation of reactive oxygen species (ROS), notably singlet oxygen (1O2). We explore PDT's intricacies, emphasizing its precise targeting of cancer cells while sparing healthy tissue. We examine the pivotal role of singlet oxygen in initiating apoptosis and other cell death pathways, highlighting its potential for minimally invasive cancer treatment. Additionally, we delve into the complex interplay of cellular components, including catalase and NOX1, in defending cancer cells against PDT-induced oxidative and nitrative stress. We unveil an intriguing auto-amplifying mechanism involving secondary singlet oxygen production and catalase inactivation, offering promising avenues for enhancing PDT's effectiveness. In conclusion, our review unravels PDT's inner workings and underscores the importance of selective illumination and photosensitizer properties for achieving precision in cancer therapy. The exploration of cellular responses and interactions reveals opportunities for refining and optimizing PDT, which holds significant potential in the ongoing fight against cancer.

Selected Cytokines and Metalloproteinases in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a collective term for two diseases: ulcerative colitis (UC) and Crohn's disease (CD). There are many factors, e.g., genetic, environmental and immunological, that increase the likelihood of these diseases. Indicators of IBDs include extracellular matrix metalloproteinases (MMPs). The aim of this review is to present data on the role of selected cytokines and metalloproteinases in IBD. In recent years, more and more transcriptomic studies are emerging. These studies are improving the characterization of the cytokine microenvironment inside inflamed tissue. It is observed that the levels of several cytokines are consistently increased in inflamed tissue in IBD, both in UC and CD. This review shows that MMPs play a major role in the pathology of inflammatory processes, cancer, and IBD. IBD-associated inflammation is associated with increased expression of MMPs and reduced ability of tissue inhibitors of metalloproteinases (TIMPs) to inhibit their action. In IBD patients in tissues that are inflamed, MMPs are produced in excess and TIMP activity is not sufficient to block MMPs. This review is based on our personal selection of the literature that was retrieved by a selective search in PubMed using the terms "Inflammatory bowel disease" and "pathogenesis of Inflammatory bowel diseases" that includes systematic reviews, meta-analyses, and clinical trials. The involvement of the immune system in the pathophysiology of IBD is reviewed in terms of the role of the cytokines and metalloproteinases involved.

Cellular Lactate Spectroscopy Using 1.5 Tesla Clinical Apparatus.

Cellular lactate is a key cellular metabolite and marker of anaerobic glycolysis. Cellular lactate uptake, release, production from glucose and glycogen, and interconversion with pyruvate are important determinants of cellular energy. It is known that lactate is present in the spectrum of neoplasms and low malignancy (without necrotic lesions). Also, the appearance of lactate signals is associated with anaerobic glucose, mitochondrial dysfunction, and other inflammatory responses. The aim of this study was the detection of lactate in cell cultures with the use of proton magnetic resonance (1H MRS) and a 1.5 Tesla clinical apparatus (MR OPTIMA 360), characterized as a medium-field system. In this study, selected metabolites, together with cellular lactate, were identified with the use of an appropriate protocol and management algorithm. This paper describes the results obtained for cancer cell cultures. This medium-field system has proven the possibility of detecting small molecules, such as lactate, with clinical instruments. 1H MRS performed using clinical MR apparatus is a useful tool for clinical analysis.

Multiple Cell Cultures for MRI Analysis.

Magnetic resonance imaging (MRI) is an imaging method that enables diagnostics. In recent years, this technique has been widely used for research using cell cultures used in pharmaceutical science to understand the distribution of various drugs in a variety of biological samples, from cellular models to tissues. MRI's dynamic development in recent years, in addition to diagnostics, has allowed the method to be implemented to assess response to applied therapies. Conventional MRI imaging provides anatomical and pathological information. Due to advanced technology, MRI provides physiological information. The use of cell cultures is very important in the process of testing new synthesized drugs, cancer research, and stem cell research, among others. Two-dimensional (2D) cell cultures conducted under laboratory conditions, although they provide a lot of information, do not reflect the basic characteristics of the tumor. To replicate the tumor microenvironment in science, a three-dimensional (3D) culture of tumor cells was developed. This makes it possible to reproduce in vivo conditions where, in addition, there is a complex and dynamic process of cell-to-cell communication and cell-matrix interaction. In this work, we reviewed current research in 2D and 3D cultures and their use in MRI studies. Articles for each section were collected from PubMed, ScienceDirect, Web of Science, and Google Scholar.

An Analysis of the Effects of In Vitro Photodynamic Therapy on Prostate Cancer Tissue by Histopathological Examination and Magnetic Resonance Imaging.

Prostate cancer can significantly shorten the lifetime of a patient, even if he is diagnosed at an early stage. The development of minimally-invasive focal therapies such as photodynamic therapy to reduce the number of neoplastic cells while sparing delicate structures is extremely advantageous for treating prostate cancer. This study investigates the effect of photodynamic therapy performed in prostate tissue samples in vitro, using quantitative magnetic resonance imaging and histopathological analysis. Prostate tissue samples were treated with oxygenated solutions of Rose Bengal (RB) or protoporphyrin IX disodium salt (PpIX), illuminated with visible light, and then analyzed for changes in morphology by microscopy and by measurement of spin-lattice and spin-spin relaxation times at 1.5 Tesla. In the treated prostate tissue samples, histopathological images revealed chromatin condensation and swelling of the stroma, and in some cases, thrombotic necrosis and swelling of the stroma accompanied by pyknotic nuclei occurred. Several samples had protein fragments in the stroma. Magnetic resonance imaging of the treated prostate tissue samples revealed differences in the spin-lattice and spin-spin relaxation times prior to and post photodynamic action.

Application of Dendrimers in Anticancer Diagnostics and Therapy.

The application of dendrimeric constructs in medical diagnostics and therapeutics is increasing. Dendrimers have attracted attention due to their compact, spherical three-dimensional structures with surfaces that can be modified by the attachment of various drugs, hydrophilic or hydrophobic groups, or reporter molecules. In the literature, many modified dendrimer systems with various applications have been reported, including drug and gene delivery systems, biosensors, bioimaging contrast agents, tissue engineering, and therapeutic agents. Dendrimers are used for the delivery of macromolecules, miRNAs, siRNAs, and many other various biomedical applications, and they are ideal carriers for bioactive molecules. In addition, the conjugation of dendrimers with antibodies, proteins, and peptides allows for the design of vaccines with highly specific and predictable properties, and the role of dendrimers as carrier systems for vaccine antigens is increasing. In this work, we will focus on a review of the use of dendrimers in cancer diagnostics and therapy. Dendrimer-based nanosystems for drug delivery are commonly based on polyamidoamine dendrimers (PAMAM) that can be modified with drugs and contrast agents. Moreover, dendrimers can be successfully used as conjugates that deliver several substances simultaneously. The potential to develop dendrimers with multifunctional abilities has served as an impetus for the design of new molecular platforms for medical diagnostics and therapeutics.

Multinuclear MRI in Drug Discovery.

The continuous development of magnetic resonance imaging broadens the range of applications to newer areas. Using MRI, we can not only visualize, but also track pharmaceutical substances and labeled cells in both in vivo and in vitro tests. 1H is widely used in the MRI method, which is determined by its high content in the human body. The potential of the MRI method makes it an excellent tool for imaging the morphology of the examined objects, and also enables registration of changes at the level of metabolism. There are several reports in the scientific publications on the use of clinical MRI for in vitro tracking. The use of multinuclear MRI has great potential for scientific research and clinical studies. Tuning MRI scanners to the Larmor frequency of a given nucleus, allows imaging without tissue background. Heavy nuclei are components of both drugs and contrast agents and molecular complexes. The implementation of hyperpolarization techniques allows for better MRI sensitivity. The aim of this review is to present the use of multinuclear MRI for investigations in drug delivery.

The Use of Photodynamic Therapy in the Treatment of Brain Tumors-A Review of the Literature.

The treatment of neoplastic disease of the brain is still a challenge for modern medicine. Therefore, advanced methodologies are needed that can rationally and successfully contribute to the early diagnosis of primary and metastatic tumors growing within the brain. Photodynamic therapy (PDT) seems to be a valuable method of treatment for precancerous and cancerous lesions including brain tumors. The main advantage of PDT is its high efficiency, minimal invasiveness and no serious side effects, compared with chemotherapy and radiotherapy. This review was conducted through a comprehensive search of articles, scientific information databases and the websites of organizations dealing with cancer treatment. Key points from clinical trials conducted by other researchers are also discussed. The common databases such as PubMed, Google Scholar, EBSCO, Scopus, and Elsevier were used. Articles in the English language of reliable credibility were mainly analyzed. The type of publications considered included clinical and preclinical studies, systematic reviews, and case reports. Based on these collected materials, we see that scientists have already demonstrated the potential of PDT application in the field of brain tumors. Therefore, in this review, the treatment of neoplasm of the Central Nervous System (CNS) and the most common tumor, glioblastoma multiforme (GBM), have been explored. In addition, an overview of the general principles of PDT, as well as the mechanism of action of the therapy as a therapeutic platform for brain tumors, is described. The research was carried out in June 2022.

Photon Upconversion in Small Molecules.

Upconversion (UC) is a process that describes the emission of shorter-wavelength light compared to that of the excitation source. Thus, UC is also referred to as anti-Stokes emission because the excitation wavelength is longer than the emission wavelength. UC materials are used in many fields, from electronics to medicine. The objective of using UC in medical research is to synthesize upconversion nanoparticles (UCNPs) composed of a lanthanide core with a coating of adsorbed dye that will generate fluorescence after excitation with near-infrared light to illuminate deep tissue. Emission occurs in the visible and UV range, and excitation mainly in the near-infrared spectrum. UC is observed for lanthanide ions due to the arrangement of their energy levels resulting from f-f electronic transitions. Organic compounds and transition metal ions are also able to form the UC process. Biocompatible UCNPs are designed to absorb infrared light and emit visible light in the UC process. Fluorescent dyes are adsorbed to UCNPs and employed in PDT to achieve deeper tissue effects upon irradiation with infrared light. Fluorescent UCNPs afford selectivity as they may be activated only by illumination of an area of diseased tissue, such as a tumor, with infrared light and are by themselves atoxic in the absence of infrared light. UCNP constructs can be monitored as to their location in the body and uptake by cancer cells, aiding in evaluation of exact doses required to treat the targeted cancer. In this paper, we review current research in UC studies and UCNP development.