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1.3.1 Diagnosis
ОглавлениеIn order to recommend adequate care, doctors must be able to distinguish healthy from diseased tissues that require the visualization of structures within the human body. This can be made possible by nanomaterials encompassing NPs which can be designed with distinct contrast properties offering better 3D visualization, employing which tissue types can be more readily distinguished. This is the main priority in nanomedicine for anatomical and functional imaging. However, NPs that are capable of visualizing biological tissues must be configured to be localized in individual tissues and theoretically deliver high contrast for use in various imaging techniques such as magnetic resonance imaging (MRI); computed tomography (CT); fluorescence imaging; and photoacoustic imaging. Material production therefore plays a crucial role in the design of smart NPs providing contrast in the region of interest; disclose information on the local environment after administration to the body and further aid in the imaging of organs, especially anatomical fine structures; help in predicting concentrations of molecules of interest; and, lastly, support in the direct internal examination of diseases in the human body (Pelaz et al. 2017).
Gold nanoparticles (AuNPs) are at the forefront of developing contrast agents to improve the sensitivity of noninvasive X‐ray imaging, CT, and micro‐CT. The high atomic number and electron density of AuNPs result in higher attenuation coefficients than iodine, a standard X‐ray contrast agent. These NPs may also be coated with targeting molecules, such as folic acid, to intensify the contact between tissues and incident rays, making it easier to illuminate distinct tissue structures. Another CT contrast agent being developed is gold nanocluster (AuNC), which has shown to exhibit excellent contrast not only for CT imaging but also for molecular imaging owing to red fluorescence emission. Thus, the CT‐based clinical diagnosis is completely revamped by these promising NPs, and NP‐based CT imaging approaches will soon be used clinically. Besides, MRI is another noninvasive medical imaging procedure routinely used to provide anatomical details. Contrasting agents traditionally used in clinical MRI include primarily paramagnetic agents (e.g. gadolinium (Gd)‐based) and superparamagnetic agents (e.g. superparamagnetic iron oxide nanoparticles [SPIONs]) (Greish et al. 2018). A substantial effort has been made to develop NPs conjugated with paramagnetic ions, such as Gd3+, Mn2+, and Fe3+, as contrast agents for MRI in an attempt to minimize toxicity, improve chemical stability, longer circulation periods, higher contrast, more regulated functionalization, and additional imaging methods. The paramagnetic NPs offer flexibility in size and shape, boost magnetic properties, and control over pharmacokinetics, potentially leading to an improvement in blood circulation time compared to conventional coordination complexes. These NPs are created either by integration into the nanostructured matrix or the post‐functionalization with the lanthanide coordination complex particles. The examples of nanoparticulate MRI contrast agents that have shown enhanced contrasting in various investigations are Gd‐doped silica NPs, Gd‐cerium NPs, Gd‐nanodiamond conjugates, Gd2O3 NPs; manganese (Mn) NPs like Mn3O4 NPs, Mn‐based double‐layered hydroxide NPs, MnO nanocomposites functionalized with porous AuNCs; dysprosium(Dy)‐modified NPs such as mesoporous silica NPs with Dy‐DOTA(1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid) chelate in the outer pore channel, Dy2O3 and DyF3 NPs, Dy(OH)3 nanorods, etc. (Pellico et al. 2019).
NP‐based radiolabels are now being developed rapidly to allow researchers to carry out and monitor quantitative biodistribution studies on systemic administration, and to investigate the basic in vivo mechanism of NPs. They are hybrid structures consisting of an organic surface coating for colloidal stabilization and targeting functionality, the operative component i.e. imaging contrast as well as the adsorbed protein layer. However, since various marking techniques and radioisotopes are used to mark NPs in order to research their fate, it is important to ensure that radioisotopes are integrated into NPs with no effect on their initial biological behavior. Picomolar amounts of nano‐size radiolabeled gold nanoshells and polymeric NPs are investigated for positron emission tomography and single‐photon emission tomography (Koziorowski et al. 2017). The richness of fluorophores makes fluorescence imaging ideal for different applications. The emission of excitation probes in this procedure can be visualized by the human eye or by optical microscopy at higher resolution. Quantum dots, rare earth‐based nanophosphors, carbon dots, nanodiamonds, etc. are the fluorescent NPs researched as contrast labels for imaging (Pratiwi et al. 2019).
The potential of designed NPs that concurrently diagnose, administer, and even control therapeutic effectiveness has increased the hopes and aspirations of diagnostic nanomedicine. NPs have a high aspect ratio, can accommodate a high drug load and can be tuned to allow combination with drugs so that a targeted, imaging‐based diagnosis can be accompanied by simultaneous therapy unique to that condition known as theranostics. It is an interesting field of research, as many diverse variations of diagnostic and therapeutic methods can be incorporated into NPs. Diagnostic application of NPs to mark cancerous cells, distinctly tumor boundaries and minor metastatic areas, can be used to direct the surgeon in the eventual removal of the tumors surgically (McDonald et al. 2015). These diagnostic NPs may also be filled with post‐surgery therapeutic agents. Additional fascinating use of nano theranostics agents for tracking, and noninvasive in vivo imaging of transporter and drug, could allow for early evaluation of the treatment response. Carbon dots, quantum dots, Gd‐DOTA, AuNPs, magnetic iron oxide NPs, ferrimagnetic nanoclusters, and nanodiamonds have high in vivo stability and are materialized as valuable tools for amalgamated diagnostic imaging and therapy. Multicompartment capsules as nanomedicine vehicles composed of smaller nanocapsules or NPs assembled under bigger particles are also investigated as an efficient mode of theranostic delivery. However, after major advances in this field, therapeutic NPs are still at an early stage of growth (Sangtani et al. 2017).
Nanotechnology provides a potential for early identification of diseases and genetic make‐up with the assistance of modest, rapid, accessible, and affordable in vitro diagnostic testing of high sensitivity. In the near future, it is predicted to have instruments that are compact and decentralized, and that need only the smallest sample size for measurement and diagnosis. Such miniaturized lab‐on‐a‐chip technique is an inexpensive boon to patients and can be used in clinics and hospitals for preventing the spread of infectious diseases (Krukemeyer et al. 2015). The overall diagnostic process is improvised using NPs having the ability to detect molecules, cells, and tissues outside the human body. For instance, modified AuNPs in combination with ligand can directly bind to a complementary protein that induces controlled agglomeration owing to the cross‐linking of the NPs by the proteins. This can be identified colorimetrically by the change of color. These AuNP‐based diagnostic concepts are refined, for example in fast colorimetric DNA sensing, and are now used in the clinic for testing of patients’ samples (Khan et al. 2020). NPs encompassing organic and inorganic polymers are also applied as handy units for intracellular sensing purposes. The rationale behind using NPs in diagnostic applications is to identify the unique biological molecules in patients’ biological liquids allied to their health. They also offer sequential detection using quantum dot‐containing microbeads to produce barcodes with special optical emission. NP‐based chemical nose sensors are also gaining interest in sera sensing, cancer cell genotyping, and the distinction between cell surface‐based bacteria. Nanomedicine in diagnostics can generate a multiplexed platform that can exploit the ability of nanomaterials to easily detect minute changes in the cell surface that enable high‐throughput screening.