Photodynamic therapy (PDT) uses photosensitizers and visible light in combination with molecular oxygen to produce reactive oxygen species (ROS) that kill malignant cells by apoptosis and/or necrosis, shut down the tumor microvasculature and stimulate the host immune system. The excited singlet state of oxygen ( 1 O 2 ) is recognized to be the main cytotoxic ROS generated during PDT for the majority of photosensitizers used clinically and for many investigational new agents, so that maximizing its production within tumor cells and tissues can improve the therapeutic response, and several emerging and novel approaches for this are summarized. Quantitative techniques for 1 O 2 production measurement during photosensitization are also of immense importance of value for both preclinical research and future clinical practice. In this review, emerging strategies for enhanced photosensitized 1 O 2 generation are introduced, while recent advances in direct detection and imaging of 1 O 2 luminescence are summarized. In addition, the correlation between cumulative 1 O 2 luminescence and PDT efficiency will be highlighted. Meanwhile, the validation of 1 O 2 luminescence dosimetry for PDT application is also considered. This review concludes with a discussion on future demands of 1 O 2 luminescence detection for PDT dosimetry, with particular emphasis on clinical translation.Eye-catching color image for graphical abstract.
The purpose of this study is to investigate the feasibility for quantitative measurement of singlet oxygen ((1)O(2)) generation by using a newly developed (1)O(2)-specific fluorescence probe Singlet Oxygen Sensor Green reagent (SOSG). (1)O(2) generation from photoirradiation of a model photosensitizer Rose Bengal (RB), in initially air-statured phosphate buffered saline (PBS) was indirectly monitored with SOSG. In the presence of (1)O(2), SOSG can react with (1)O(2) to produce SOSG endoperoxides (SOSG-EP) that emit strong green fluorescence with the maximum at 531 nm. The green fluorescence of SOSG-EP is mainly dependent on the initial concentrations of RB and SOSG, and the photoirradiation time for (1)O(2) generation. Furthermore, kinetic analysis of the RB-sensitized photooxidation of SOSG is performed that, for the first time, allows quantitative measurement of (1)O(2) generation directly from the determination of reaction rate. In addition, the obtained (1)O(2) quantum yield of porphyrin-based photosensitizer hematoporphyrin monomethyl ether (HMME) in PBS by using SOSG is in good agreement with the value that independently determined by using direct measurement of (1)O(2) luminescence. The results of this study clearly demonstrate that the quantitative measurement of (1)O(2) generation using SOSG can be achieved by determining the reaction rate with an appropriate measurement protocol.
Fluorescence (FL) imaging and photodynamic therapy (PDT) are popular in the diagnosis and treatment of diseases, respectively, especially in cancer. The excitation of the laser in the second near‐infrared (NIR‐II) window can effectively avoid the interference of spontaneous fluorescence and light scattering of tissues, obtaining high‐resolution images at deeper penetration depth. Due to their ideal spectral absorbance and high conversion efficiency, nanomaterials with emission at NIR‐II window not only overcome the absorption or emission of NIR‐II light by endogenous biomolecules, but also facilitate NIR‐II FL imaging and the application of photodynamic therapy (PDT). The research progress of NIR‐II nanomaterials for FL imaging and PDT in recent years is reviewed. First, the NIR‐II FL imaging of several representative organic and inorganic materials is introduced, including their remarkable properties and synthesis methods. Then, the use of NIR‐II nanomaterials in PDT, such as NIR‐II FL imaging‐guided PDT, and PDT combined with photothermal therapy is described. Finally, some critical challenges and open problems are proposed that need to be addressed in synthetic technology and clinical application.
In the case of hepatocellular carcinoma (HCC) samples, classification of differentiation is crucial for determining prognosis and treatment strategy decisions. However, a label‐free and automated classification system for HCC grading has not been yet developed. Hence, in this study, we demonstrate the fusion of multiphoton microscopy and a deep‐learning algorithm for classifying HCC differentiation to produce an innovative computer‐aided diagnostic method. Convolutional neural networks based on the VGG‐16 framework were trained using 217 combined two‐photon excitation fluorescence and second‐harmonic generation images; the resulting classification accuracy of the HCC differentiation grade was over 90%. Our results suggest that a combination of multiphoton microscopy and deep learning can realize label‐free, automated methods for various tissues, diseases and other related classification problems.
Photoacoustic imaging (PAI) has attracted great attention in the diagnosis and treatment of diseases due to its noninvasive properties. Especially in the second near-infrared (NIR-II) window, PAI can effectively avoid the interference of tissue spontaneous fluorescence and light scattering, and obtain high resolution images with deeper penetration depth. Because of its ideal spectral absorption and high conversion efficiency, NIR-II PA contrast agents overcome the absorption or emission of NIR-II light by endogenous biomolecules. In recent years, a series of NIR-II PA contrast agents have been developed to improve the performance of PAI in disease diagnosis and treatment. In this paper, the research progress of NIR-II PA contrast agents and their applications in biomedicine are reviewed. PA contrast agents are classified according to their composition, including inorganic contrast agents, organic contrast agents, and hybrid organic−inorganic contrast agents. The applications of NIR-II PA contrast agents in medical imaging are described, such as cancer imaging, inflammation detection, brain disease imaging, blood related disease imaging, and other biomedical application. Finally, the research prospects and breakthrough of NIR-II PA contrast agents are discussed.
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