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Early detection of malignant tumors, micrometastases, and disseminated tumor cells is one of the effective way of fighting cancer. Among the many existing imaging methods like computed tomography (CT), ultrasound (US), magnetic resonance imaging (MRI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT), optic...
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... Первая группа методов позволяет детектировать опухоли размером от нескольких миллиметров, а также устанавливать их локализацию, но при этом требуют использования дорогостоящего оборудования и применяются для скрининга только отдельных типов ОЗ. В то же время методы молекулярной диагностики позволяют детектировать даже единичные раковые клетки [4]. В частности, A. M. Lutz и соавт. ...
Introduction. Early sensitive and highly specific diagnosis is crucial for successful cancer therapy. The use of fluorescent hydrogels (FHG) makes it possible to develop versatile biosensors due to the increased binding capacity of biological capture and reporter molecules, sensitive fluorescence detection, and the flexibility of combining their structural and functional elements.
Aim. Analyzing the principles of designing biosensors based on FHG for the detection of cancer markers and the methodological approaches to their development, as well as summarizing and systematizing the data on the principles of detection and target signal generation used in these sensors.
Results. FHG represent 3D sensing platforms, i. e., structures that combine the reporter fluorescence function with biological capture molecules, allowing the unique optical properties of fluorescent nanocrystals at the macro level to be preserved. The porous structure of hydrogels increases the active surface area of biosensors for 3D immobilization of fluorescent labels and biological capture molecules, while preserving the structure of these molecules, which ensures specific binding of the detected molecules of the sample. This ensures a higher sensitivity compared with the traditional methods of immunoenzymatic and immunochromatographic analyses. Not only the traditionally used antibodies, but also enzymes and glycoproteins, aptamers and oligonucleotides, as well as polymers obtained by molecular imprinting, can serve as biological capture molecules, which extends the range of specifically detectable analytes.
Conclusion. The review presents examples of biosensors based on FHG intended for the detection of cancer markers and describes approaches to the preparation of FHG and immobilization of biological capture molecules, as well as principles of generation of the detected optical signal. The main advantages of fluorescent hydrogel biosensors over the classical tests used for quick diagnosis of cancer are shown.
... The low immunogenicity of adAbs makes it possible to create not only highly specific drugs based on them but also create vesicles for target delivery of pharmaceutical compounds and diagnostics. There are many examples of using sdAbs as targeting agents in vivo for cancer cell and metastasis detection by optical methods [174] or by SPECT/CT [175,176]. Recently, Feng at al. investigated 131 I-labeled anti-HER2 sdAb for the radiopharmaceutical therapy of HER2-expressing BC in mice [177]. ...
Multiplexed fluorescent immunohistochemical analysis of breast cancer (BC) markers and high-resolution 3D immunofluorescence imaging of the tumor and its microenvironment not only facilitate making the disease prognosis and selecting effective anticancer therapy (including photodynamic therapy), but also provides information on signaling and metabolic mechanisms of carcinogenesis and helps in the search for new therapeutic targets and drugs. The characteristics of imaging nanoprobe efficiency, such as sensitivity, target affinity, depth of tissue penetration, and photostability, are determined by the properties of their components, fluorophores and capture molecules, and by the method of their conjugation. Regarding individual nanoprobe components, fluorescent nanocrystals (NCs) are widely used for optical imaging in vitro and in vivo, and single-domain antibodies (sdAbs) are well established as highly specific capture molecules in diagnostic and therapeutic applications. Moreover, the technologies of obtaining functionally active sdAb–NC conjugates with the highest possible avidity, with all sdAb molecules bound to the NC in a strictly oriented manner, provide 3D-imaging nanoprobes with strong comparative advantages. This review is aimed at highlighting the importance of an integrated approach to BC diagnosis, including the detection of biomarkers of the tumor and its microenvironment, as well as the need for their quantitative profiling and imaging of their mutual location, using advanced approaches to 3D detection in thick tissue sections. The existing approaches to 3D imaging of tumors and their microenvironment using fluorescent NCs are described, and the main comparative advantages and disadvantages of nontoxic fluorescent sdAb–NC conjugates as nanoprobes for multiplexed detection and 3D imaging of BC markers are discussed.
