MedNexus
2020年 · 第03卷第04期
MedNexus
Coronavirus disease 2019 (COVID-19) is a newly emerged infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of COVID-19 cases is continuously increasing and no effective drugs or vaccines are currently available. Accurate and efficient diagnostic testing methods are desperately needed for the detection of SARS-CoV-2 and antiviral antibodies in infected individuals. Various assay techniques, including nucleic acid tests [eg, polymerase chain reaction (PCR), reverse transcription-PCR, real-time loop-mediated isothermal amplification, and CRISPR-Cas-based detection], serological tests [eg, immunoglobulin (Ig)A, IgM/G], imaging tests (eg, computed tomography and positron-emission tomography), and nanoparticle-based detections have been reported for COVID-19 diagnosis. This review aims to present the current diagnostic tools for SARS-CoV-2 and their performance characteristics to inform the appropriate selection of diagnostic and surveillance technologies at optimal testing times. We also describe the advantages of detection using combined nucleic acid and imaging tests, or serological testing and point-of-care diagnostics. Developing reliable protein biomarkers targeting the conserved proteins of SARS-CoV-2 rather than IgA, IgM, or IgG would be useful to manage SARS-CoV-2.
Single-domain antibodies have the characteristics of small molecular weight, strong tissue penetration, and high affinity, and are widely used to construct molecular probes for disease diagnosis and treatment. This article reviews molecular imaging studies including positron emission tomography (PET), single-photon emission computed tomography/computed tomography (CT), PET/CT, and fluorescent imaging of molecular probes composed of single-domain antibodies against eight esophageal squamous cell carcinoma biological targets. These 8 targets are highly expressed on the membrane of esophageal squamous cell carcinoma cells and include epidermal growth factor receptor, human epidermal growth factor receptor 2, human epidermal growth factor receptor 3, hepatocyte growth factor receptor, vascular endothelial growth factor receptor 2, chemokine receptor 4, chemokine receptor 7, and carcinoembryonic antigen. The current problems and solutions are also discussed to provide a reference for future design of molecular imaging probes targeting esophageal squamous cell carcinoma.
Molecular imaging is of great significance for early diagnosis and timely treatment of cancer and disease, as well as basic medical and biological research. As personalized cancer treatment has become increasingly popular, the demand for more advanced imaging technologies has also significantly increased. Taking advantage of differences between the tumor microenvironment and normal tissue cells, tumor microenvironment-responsive or "turn-on" contrast agents have a higher signal-to-noise ratio and lower background interference compared with "turn-off" probes, which can remarkably improve the performance of tumor diagnostics. Thus, tumor microenvironment-responsive contrast agents can not only detect changes in the tumor microenvironment, but also have important significance for tumor diagnosis, prediction of invasion potential, evaluation of treatment effectiveness, planning of therapeutic regimens, and tumor prognosis. Herein, this review focuses on recent research progress of tumor microenvironment-responsive intelligent probes, and highlights future research directions of tumor microenvironment-responsive contrast agents for precision diagnostics.
Inflammatory bowel disease (IBD), such as Crohn disease and ulcerative colitis, are chronic relapsing disorders of the gastrointestinal tract. Characterized pathologically by intestinal inflammation and epithelial injury, great challenges exist for the treatment of IBD due to its complicated etiology and incurable nature. Traditional strategies rely on frequent and long-term administration of high dosages of anti-inflammatory drugs, which inevitably cause side effects. Therefore, novel therapeutic methods and drug delivery systems capable of improving therapeutic effect while simultaneously decreasing side effects need to be developed. The emergence of nanotechnology provides alternative approaches for diagnosis and treatment of IBD, as nanoparticles (NPs) have unique physicochemical properties such as targeting to the site of inflammation and the ability to alter the pharmacokinetics of traditional drugs. This review first introduces the pathophysiological features and microenvironment of IBD, and then summarizes different strategies and mechanisms of NP-based colon-targeted drug delivery systems, including size-dependent, multi-stimuli responsive, active targeting, intestinal microbiota-related, and novel natural-derived NP-mediated drug delivery systems. We also discuss applications of nanozymes and NP-based imaging in diagnostics and treatment of IBD. Finally, challenges and prospects in the field are proposed to promote the development of targeted drug delivery for IBD treatment.
Luminescence (mostly fluorescence and phosphorescence) probes are a powerful tool widely used in the life sciences research. They can be used, for example, in the quantitative analysis of physiological parameters, visualization of different cell organelles, and measurement of drug transportation. The luminescence intensity and lifetime of these probes are among the main signals recorded and evaluated in these applications. Other reviews have discussed optical probes from the perspective of their luminescence intensity. However, the luminescence lifetime, which depends on the molecular microenvironment but not the probe concentration, is another promising metric for biological sensing and imaging applications. In this review, we aim to introduce the basic strategies of FLIM probe design. We also present applications of these probes, including sensing of intracellular pH, cation/anion concentrations, oxygen levels, biomolecule contents, and physiological parameters, as well as live-cell imaging based on luminescence lifetime. Studies based on FLIM imaging of cells or tissues with endogenous organic molecules are not included in this mini review. With the rapid development of microscopy technology for fluorescence lifetime imaging, fluorescence lifetime-based probes have shown great potential in a variety of biological applications.
Glioma is the most common and aggressive primary brain tumor. Here, we aimed to establish a nano-drug carrier system to traverse the blood-brain barrier for the treatment and inhibition of glioma migration.
The synthesis of bovine serum albumin protected-silver nanoclusters (BSA-AgNCs) was performed using chemical reduction. The drug paclitaxel (PTX) can be loaded into BSA-AgNCs through electrostatic and hydrophobic interactions to formulate spherical BSA-AgNC-PTX nanoparticles (BSA-AgNC-PTX NPs). A glioma mouse model was established by injecting U251-GFP-Luc cells into the mouse striatum, and all surgical procedures were approved by the Animal Ethics Committee of Nanchang University (SYXK2019-0003) on December 29, 2019.
The BSA-AgNC-PTX NPs were able to efficiently pass through the blood-brain barrier, both in vitro and in vivo, to deliver the drug to the tumor site. The in vivo assessment of BSA-AgNC-PTX NPs in glioblastoma multiforme-bearing mice revealed the significant inhibition of tumor growth and migration, prolonging the survival of the mice.
These results indicated that BSA-AgNCs might represent an ideal nanocarrier for the treatment of glioma and has the potential to be used in the treatment of a variety of central nervous system diseases.
Immunotherapy is an effective tumor treatment strategy. However, its long treatment cycle limits its wide application across all cancer types. In this study, we optimized upconversion nanoparticles and manganese composite particles with a porous structure as a nanoplatform for synergistic photodynamic therapy (PDT) and photothermal therapy (PTT), and subsequent longer-term immunotherapy.
The morphology, phase, and stability were first characterized to evaluate the biocompatibility of this material. The upconversion and near infrared II luminescence properties of the material and its stimuli-response effect were assessed from the absorbance and photoluminescence spectra. Phototherapy including PDT and PTT was demonstrated in vitro and in vivo, and immunotherapy was used to enhance the phototherapy. This study was approved by the Xi’an Jiaotong University, China (approval No. XJTULAC2020-585) on April 2, 2020.
The nanoplatform showed good PDT and PTT effects with high upconversion luminescence, and exhibited a more sensitive glutathione response (detection limit: 55 μg/mL) using fluorescence recovery than that based on absorbance recovery, with the detection range extending up to 1.2 mg/mL. When the surface of the composite particles was modified with an anti-PD-L1 immune checkpoint inhibitor, it targeted A549 lung cancer cells. The resulting immune response enhanced the long-term anti-tumor effect of the therapy, especially in lung cancer patients with high PD-L1 expression.
The designed composite can be simultaneously used to detect the glutathione concentration based on luminescence recovery in the tumor cells and as a theranostic nanoplatform for synergistic immuno-phototherapy when combined with an antibody.
In order to study the important role and molecular mechanism of Brevinin-2 family antimicrobial peptide Brevinin-2ISb in methicillin-resistant Staphylococcus aureus (MRSA) infection of Caenorhabditis (C.) elegans, and to find the optimal therapeutic concentration of Brevinin-2ISb.
By using a C. elegans model and MRSA infection modelto study the therapeutic effect of different concentrations of Brevinin-2ISb on C. elegans. Real-time PCR was used for investigating the effect of Brevinin-2ISb on the downstream gene expression of DAF-2/DAF-16 innate immune pathway and the major virulence factor gene expression of MRSA. With protein activity tests to study the inhibitory effect of Brevinin-2ISb on MRSA virulence factor protein activity. Finally, laser confocal imaging was carried out to observe real-time expression and distribution of downstream antimicrobial proteins to further prove the effect of Brevinin-2ISb on the activation of DAF-2/DAF-16 pathway by in vivo imaging. All animal study procedures were approved by the Academic Committee at Xidian University and Xi’an Jiaotong University Animal Care and Use Committee, China (approval No. JGC201207) on July 15, 2017.
Host immunity was largely enhanced by Brevinin-2ISb, and the expression of staphylococcal enterotoxin genes, as well as virulence factors, was suppressed by Brevinin-2ISb. Indeed, the expression of many C. elegans innate immune genes, including lys-7, spp-1, K05D8.5 and C29F3.7, was induced by Brevinin-2ISb. In particular, robust, sustained expression of the antibacterial gene lys-7 was observed after Brevinin-2ISb treatment, resulting in increased protein levels. These effects correlated with a reduction in the MRSA-mediated death of the C. elegans host. Low concentrations of Brevinin-2ISb exhibited very low hemolytic activity, and may play a positive role in host innate immunity. Specifically, activation of the DAF-2/DAF-16 pathway appears to be essential for immune activation in C. elegans treated with Brevinin-2ISb. Based on the evolutionary conservation of innate immune pathways, our results suggest that Brevinin-2ISb not only has strong antibacterial activity, but may also enhance the innate immune response in humans. This study demonstrates that Brevinin-2ISb-related peptides are potential candidates for the development of novel anti-inflammatory or anti-microbial drugs.
Antimicrobial peptide Brevinin-2ISb effectively inhibits MRSA at low concentration. This antimicrobial peptide can prolong the life of MRSA-infected C. elegans, has very low hemolytic activity and inhibits the activity and expression of various MRSA virulence factors. More importantly, Brevinin-2ISb activated the expression of antimicrobial genes downstream of DAF-2/DAF-16, which enhanced the MRSA resistance of C. elegans. This peptide could be used as the basis for developing new drugs to replace antibiotics.
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