Manganese-based nanomaterials in diagnostics and chemodynamic therapy of cancers: new development.

In the realm of cancer treatment, traditional modalities like radiotherapy and chemotherapy have achieved certain advancements but continue to grapple with challenges including harm to healthy tissues, resistance to treatment, and adverse drug reactions. The swift progress in nanotechnology recently has opened avenues for investigating innovative approaches to cancer therapy. Especially, chemodynamic therapy (CDT) utilizing metal nanomaterials stands out as an effective cancer treatment choice owing to its minimal side effects and independence from external energy sources. Transition metals like manganese are capable of exerting anti-tumor effects through a Fenton-like mechanism, with their distinctive magnetic properties playing a crucial role as contrast agents in tumor diagnosis and treatment. Against this backdrop, this review emphasizes the recent five-year advancements in the application of manganese (Mn) metal ions within nanomaterials, particularly highlighting their unique capabilities in catalyzing CDT and enhancing MRI imaging. Initially, we delineate the biomedical properties of manganese, followed by an integrated discussion on the utilization of manganese-based nanomaterials in CDT alongside multimodal therapies, and delve into the application and future outlook of manganese-based nanomaterial-mediated MRI imaging techniques in cancer therapy. By this means, the objective is to furnish novel viewpoints and possibilities for the research and development in future cancer therapies.

Porphyrin-based covalent organic framework as oxidase mimic for highly sensitive colorimetric detection of pesticides.

A covalent organic framework-based strategy was designed for label-free colorimetric detection of pesticides. Covalent organic framework-based nanoenzyme with excellent oxidase-like catalytic activity was synthesized. Unlike other artificial enzymes, porphyrin-based covalent organic framework (p-COF) as the oxidase mimic showed highly catalytic chromogenic activity and good affinity toward TMB without the presence of H2O2, which can be used as substitute for peroxidase mimics and H2O2 system in the colorimetric reaction. Based on the fact that the pesticide-aptamer complex can inhibit the oxidase activity of p-COF and reduced the absorbance at 650 nm in UV-Vis spectrum, a label-free and facile colorimetric detection of pesticides was designed and fabricated. Under the optimized conditions, the COF-based colorimetric probe for pesticide detection displayed high sensitivity and selectivity. Taking fipronil for example the limit of detection was 2.7 ng/mL and the linear range was 5 -500,000 ng/mL. The strategy was successfully applied to the detection of pesticides with good recovery , which was in accordance with that of HPLC-MS/MS. The COF-based colorimetric detection was free of complicated modification H2O2, which guaranteed the accuracy and reliability of measurements. The COF-based sensing strategy is a potential candidate for the sensitive detection of pesticides of interests.

Sample-to-answer salivary miRNA testing: New frontiers in point-of-care diagnostic technologies.

MicroRNA (miRNA), crucial non-coding RNAs, have emerged as key biomarkers in molecular diagnostics, prognosis, and personalized medicine due to their significant role in gene expression regulation. Salivary miRNA, in particular, stands out for its non-invasive collection method and ease of accessibility, offering promising avenues for the development of point-of-care diagnostics for a spectrum of diseases, including cancer, neurodegenerative disorders, and infectious diseases. Such development promises rapid and precise diagnosis, enabling timely treatment. Despite significant advancements in salivary miRNA-based testing, challenges persist in the quantification, multiplexing, sensitivity, and specificity, particularly for miRNA at low concentrations in complex biological mixtures. This work delves into these challenges, focusing on the development and application of salivary miRNA tests for point-of-care use. We explore the biogenesis of salivary miRNA and analyze their quantitative expression and their disease relevance in cancer, infection, and neurodegenerative disorders. We also examined recent progress in miRNA extraction, amplification, and multiplexed detection methods. This study offers a comprehensive view of the development of salivary miRNA-based point-of-care testing (POCT). Its successful advancement could revolutionize the early detection, monitoring, and management of various conditions, enhancing healthcare outcomes. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices.

Extracellular vesicles derived from immune cells: Role in tumor therapy.

Extracellular vesicles (EVs), which have a lipid nano-sized structure, are known to contain the active components of parental cells and play a crucial role in intercellular communication. The progression and metastasis of tumors are influenced by EVs derived from immune cells, which can simultaneously stimulate and suppress immune responses. In the past few decades, there has been a considerable focus on EVs due to their potential in various areas such as the development of vaccines, delivering drugs, making engineered modifications, and serving as biomarkers for diagnosis and prognosis. This review focuses on the substance information present in EVs derived from innate and adaptive immune cells, their effects on the immune system, and their applications in cancer treatment. While there are still challenges to overcome, it is important to explore the composition of immune cells released vesicles and their potential therapeutic role in tumor therapy. The review also highlights the current limitations and future prospects in utilizing EVs for treatment purposes.

Improving the therapeutic efficacy of oncolytic viruses for cancer: targeting macrophages.

Oncolytic viruses (OVs) for cancer treatment are in a rapid stage of development, and the direct tumor lysis and activation of a comprehensive host immune response are irreplaceable advantages of cancer immunotherapy. However, excessive antiviral immune responses also restrict the spread of OVs in vivo and the infection of tumor cells. Macrophages are functionally diverse innate immune cells that phagocytose tumor cells and present antigens to activate the immune response, while also limiting the delivery of OVs to tumors. Studies have shown that the functional propensity of macrophages between OVs and tumor cells affects the overall therapeutic effect of oncolytic virotherapy. How to effectively avoid the restrictive effect of macrophages on OVs and reshape the function of tumor-associated macrophages in oncolytic virotherapy is an important challenge we are now facing. Here, we review and summarize the complex dual role of macrophages in oncolytic virotherapy, highlighting how the functional characteristics of macrophage plasticity can be utilized to cooperate with OVs to enhance anti-tumor effects, as well as highlighting the importance of designing and optimizing delivery modalities for OVs in the future.

Quality assessment of transperineal ultrasound in Chinese tertiary medical centers: a multicenter study.

Background: Transperineal ultrasound (TPUS) is a vital examination method for diagnosing pelvic floor diseases. However, the quality of TPUS largely relies on the operator's experience, and there is a lack of studies on the evaluation of TPUS quality. Therefore, the objective of this study was to assess the quality of TPUS examinations in Chinese tertiary medical centers. Methods: This multicenter study conducted in 44 Chinese tertiary medical centers recruited postpartum women between September 2020 and September 2021. All participants underwent a standardized inquiry and TPUS examination. The participating centers were required to submit 5 parts of ultrasound data to the National Ultrasound Quality Control Center: 2-dimensional images at rest, 2-dimensional images at strain; 4-dimensional images of the levator ani hiatus; 4-dimensional images of the levator ani muscle; and 4-dimensional images of the anal sphincter. Quality assessment was performed by 2 experts with more than 5 years of experience in TPUS, and the reasons for nonqualification were stated. Results: In this study, 31 hospitals that were distributed across 20 provinces in China were included, submitting 2,251 cases in total. The overall qualified rate ranged from 12.00% to 86.92%. In each part, the qualified rate of 2-dimensional images at rest, 2-dimensional images at straining, levator ani hiatus, levator ani muscle, and anal sphincter was 94.27% (2,122/2,251), 78.54% (1,768/2,251), 85.52% (1,925/2,251), 93.03% (2,094/2,251), and 88.09% (1,983/2,251), respectively. Most of the nonqualified images belonged to 2-dimensional images at strain, and the errors in image acquisition (221/483, 45.76%) and measurement (262/483, 54.24%) were the main reasons for nonqualification. For levator ani hiatus images, error in image acquisition (275/326, 84.36%) was the main reason for nonqualification. Reconstruction error was the most common reason for nonqualification for levator ani muscle (133/157, 84.71%) and anal sphincter images (133/268, 49.63%). Conclusions: This multicenter study assessed the quality of TPUS in tertiary medical centers in China and identified the common reasons for nonqualification in each part. These findings can aid in forming the basis for quality control management and training for TPUS.

A narrative review: progress in transition metal-mediated bioorthogonal catalysis for the treatment of solid tumors.

Background and Objective: Transition metals are commonly used catalysts in bioorthogonal chemistry and have attracted extensive attention in biochemistry because of their efficient catalytic performance. In recent years, transition metal-mediated cycloaddition reactions, bond cleavage, and formation reactions are being actively explored for tumor treatment. However, the direct application of transition metals in complex biological environments has several problems, including poor solubility, toxicity, and easy inactivation. The combination of transition metals and nanomaterials can solve those problems by playing a bioorthogonal catalytic role in tumor treatment. In this review, we summarize some research on the application of transition metals modified by nanomaterials in tumor therapy and discuss the potential and challenges of transition metal-mediated bioorthogonal therapy in comprehensive tumor therapy. Methods: English literature on transition metal in cancer treatment was searched in PubMed and Web of Science. The main search terms were "cancer treatment", "bioorthogonal reaction", "transition metal", "bioorthogonal catalysis", etc. Key Content and Findings: This review summarizes research on several major transition metals that can be used for bioorthogonal catalysis with the assistance of nanomaterials in anti-tumor therapy. In addition, bioorthogonal catalysis is a new supplement to antitumor therapy. We have compiled the potential challenges of the clinical application of transition metal-based nanocatalysts, which lays the foundation for future research related to medicinal chemistry and targeted cancer therapy. Conclusions: Most of the transition metals still have a lot of room for exploration in cancer treatment research. We still need more research to confirm the feasibility of in vivo and clinical trials.

Signal Amplification-Based Biosensors and Application in RNA Tumor Markers.

Tumor markers are important substances for assessing cancer development. In recent years, RNA tumor markers have attracted significant attention, and studies have shown that their abnormal expression of post-transcriptional regulatory genes is associated with tumor progression. Therefore, RNA tumor markers are considered as potential targets in clinical diagnosis and prognosis. Many studies show that biosensors have good application prospects in the field of medical diagnosis. The application of biosensors in RNA tumor markers is developing rapidly. These sensors have the advantages of high sensitivity, excellent selectivity, and convenience. However, the detection abundance of RNA tumor markers is low. In order to improve the detection sensitivity, researchers have developed a variety of signal amplification strategies to enhance the detection signal. In this review, after a brief introduction of the sensing principles and designs of different biosensing platforms, we will summarize the latest research progress of electrochemical, photoelectrochemical, and fluorescent biosensors based on signal amplification strategies for detecting RNA tumor markers. This review provides a high sensitivity and good selectivity sensing platform for early-stage cancer research. It provides a new idea for the development of accurate, sensitive, and convenient biological analysis in the future, which can be used for the early diagnosis and monitoring of cancer and contribute to the reduction in the mortality rate.

Electrochemical Sensor Based on Nanomaterials and Its Application in the Detection of Alpha Fetoprotein.

Hepatocellular carcinoma development and many other tumors are closely related to alpha-fetoprotein (AFP), its determination can be used as a positive test for tumors. It is mainly used clinically as a serum marker to diagnose and monitor the efficacy of primary hepatocellular carcinoma. Therefore, a variety of biosensors have been developed to detect AFP. Electrochemical sensors integrate a variety of detection methods. They have inherent advantages over other types of sensors, they are fast, portable, simple, and highly sensitive. Some meaningful electrochemical biosensors work with nanomaterials acting as signal amplification elements or as signal amplification catalysts. This review introduced the field of biosensors and discuss about the use of nanomaterials in electrochemical sensing, specificity electrochemical biosensing of AFP. The study ends with a discussion about the prospects for nanomaterial-based signal amplification and future research directions.

Autophagy-mediated nanomaterials for tumor therapy.

Autophagy is a lysosomal self-degradation pathway that plays an important protective role in maintaining intracellular environment. Deregulation of autophagy is related to several diseases, including cancer, infection, neurodegeneration, aging, and heart disease. In this review, we will summarize recent advances in autophagy-mediated nanomaterials for tumor therapy. Firstly, the autophagy signaling pathway for tumor therapy will be reviewed, including oxidative stress, mammalian target of rapamycin (mTOR) signaling and autophagy-associated genes pathway. Based on that, many autophagy-mediated nanomaterials have been developed and applied in tumor therapy. According to the different structure of nanomaterials, we will review and evaluate these autophagy-mediated nanomaterials' therapeutic efficacy and potential clinical application.

A luminescent probe based on terbium-based metal-organic frameworks for organophosphorus pesticides detection.

Terbium-based metal-organic frameworks (Tb-MOF) prepared under mild conditions was utilized to construct a fluorescence probe for determination of organophosphorus pesticides (OPs) coupled with acetylcholinesterase (AChE), acetylcholine chloride (Ach), and choline oxidase (CHO). Since OPs have obvious inhibition on the activity of AChE in the Tb-MOF/ACh/CHO/AChE system, the detection of OPs was accomplished by restoring the fluorescence of Tb-MOF resulting from reduced production of H2O2. By taking chlorpyrifos (CPF) as a pesticide model, the method exhibits high sensitivity in the linear range 0.1-4.0 µg·L-1 with the limit of detection (LOD) of 0.04 µg·L-1 under optimum conditions (λex = 280 nm, λem = 544 nm). The Tb-MOF/ACh/CHO/AChE fluorescence system has high selectivity for CPF. The method was successfully applied to the detection of CPF in tap water and strawberry samples (recovery of 87.36-115.60% for tap water and 95.04-103.20% for strawberry). Free from complicated fabrication operation, the Tb-MOF-based system is rapid, simple, and stable, which provides a reference and new way for the design of OPs fluorescent probes in the future.

Enantioselective para-C(sp2 )-H Functionalization of Alkyl Benzene Derivatives via Cooperative Catalysis of Gold/Chiral Brønsted Acid.

An asymmetric para-C(sp2 )-H bond functionalization of alkyl benzene derivatives was successfully developed via cooperative catalysis of gold and chiral phosphoric acid (CPA), leading to synthetically useful chiral 1,1-diaryl motifs. Chiral phosphoric acid, ligand, and molecular sieves were found to be crucial for enantioselectivity control of this transformation. The salient features of this protocol include mild conditions, high efficiency, commercially available starting materials, highly chemo- and site- as well as enantioselective aromatic C-H functionalization, broad substrate scope, and extensive applications of the chiral products. The mechanistic studies suggested that two CPAs might be involved in chiral induction.

Generation of αGal-enhanced bifunctional tumor vaccine.

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis and high mortality. In this study, we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine α-1,3-galactose epitopes (αGal) and endorphin extracellular domains (END) with dendritic cells (DCs) from healthy volunteers. END+/Gal+-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes (CTLs) and secretion of interferon-gamma (IFN-γ). CTLs targeted cells expressing αGal and END and tumor angiogenesis. The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice, indicating the high clinical potential of this new cell based vaccine.

Streamlined Alkylation via Nickel-Hydride-Catalyzed Hydrocarbonation of Alkenes.

Compounds rich in sp3-hybridized carbons are desirable in drug discovery. Nickel-catalyzed hydrocarbonation of alkenes is a potentially efficient method to synthesize these compounds. By using abundant, readily available, and stable alkenes as pro-nucleophiles, these reactions can have broad scope and high functional group tolerance. However, this methodology is still in an early stage of development, as the first efficient examples were reported only in 2016. Herein, we summarize the progress of this emerging field, with an emphasis on enantioselective reactions. We highlight major developments, critically discuss a wide range of possible mechanisms, and offer our perspective of the state and challenges of the field. We hope this Perspective will stimulate future works in this area, making the methodology widely applicable in organic synthesis.

Platelets for cancer treatment and drug delivery.

Extensive research is currently being conducted into a variety of bio-inspired biomimetic nanoparticles (NPs) with new cell simulation functions across the fields of materials science, chemistry, biology, physics, and engineering. Cells such as erythrocytes, platelets, and stem cells have been engineered as new drug carriers. The platelet-derived drug delivery system, which is a new targeted drug delivery system (TDDS), can effectively navigate the blood circulatory system and interact with the complex tumor microenvironment; it appears to outperform traditional anticancer drugs; hence, it has attracted considerable research interest. In this review, we describe innovative studies and outline the latest progress regarding the use of platelets as tumor targeting and drug delivery vehicles; we also highlight opportunities and challenges relevant to the manufacture of tumor-related platelet TDDSs.

Controlled moisture permeability of thermoplastic starch/polylactic acid/poly butylene adipate-co-terephthalate film for the autolysis of straw mushroom Volvariella volvacea.

Straw mushrooms are prone to autolyze, leading to a high requirement of environmental humidity. In this work, thermoplastic starch/polylactic acid/poly (butylene adipate-co-terephthalate) (TPS/PLA/PBAT) film was produced by extrusion. The moisture permeability of the film was controlled by adjusting the content of TPS, which could be expected to further control humidity of the microenvironment in the package. Results revealed that the water vapor transmission rate of the film linearly increased from 612.31 g/m2·24 h to 1082.50 g/m2·24 h with the increase in the TPS concentration. The TPS/PLA/PBAT film with 30 wt% TPS showed the strongest inhibition on the autolysis of straw mushrooms compared with other groups, effectively delaying the increase in the free water, soluble solid content, rate of weight loss, and polyphenol oxidase of straw mushrooms and extending the shelf life of straw mushrooms from 24 h to 72 h.

Aptamer-based biosensors and application in tumor theranostics.

An aptamer is a short oligonucleotide chain that can specifically recognize targeting analytes. Due to its high specificity, low cost, and good biocompatibility, aptamers as the targeting elements of biosensors have been applied widely in non-invasive tumor imaging and treatment in situ to replace traditional methods. In this review, we will summarize recent advances in using aptamer-based biosensors in tumor diagnosis. After a brief introduction of the advantage of aptamers compared with enzyme sensors and immune sensors, the different sensing designs and mechanisms based on 3 signal transduction modes will be reviewed to cover different kinds of analytical methods, including: electrochemistry analysis, colorimetry analysis, and fluorescence analysis. Finally, the prospective advantages of aptamer-based biosensors in tumor theranostics and post-treatment monitoring are also evaluated in this review.

Generation of in situ CRISPR-mediated primary and metastatic cancer from monkey liver.

Non-human primates (NHPs) represent the most valuable animals for drug discovery. However, the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simulating human diseases, such as cancer. This study generated an in situ gene-editing approach to induce efficient loss-of-function mutations of Pten and p53 genes for rapid modeling primary and metastatic liver tumors using the CRISPR/Cas9 in the adult cynomolgus monkey. Under ultrasound guidance, the CRISPR/Cas9 was injected into the cynomolgus monkey liver through the intrahepatic portal vein. The results showed that the ultrasound-guided CRISPR/Cas9 resulted in indels of the Pten and p53 genes in seven out of eight monkeys. The best mutation efficiencies for Pten and p53 were up to 74.71% and 74.68%, respectively. Furthermore, the morbidity of primary and extensively metastatic (lung, spleen, lymph nodes) hepatoma in CRISPR-treated monkeys was 87.5%. The ultrasound-guided CRISPR system could have great potential to successfully pursue the desired target genes, thereby reducing possible side effects associated with hitting non-specific off-target genes, and significantly increasing more efficiency as well as higher specificity of in situ gene editing in vivo, which holds promise as a powerful, yet feasible tool, to edit disease genes to build corresponding human disease models in adult NHPs and to greatly accelerate the discovery of new drugs and save economic costs.

Current Strategies for Tumor Photodynamic Therapy Combined With Immunotherapy.

Photodynamic therapy (PDT) is a low invasive antitumor therapy with fewer side effects. On the other hand, immunotherapy also has significant clinical applications in the treatment of cancer. Both therapies, on their own, have some limitations and are incapable of meeting the demands of the current cancer treatment. The efficacy of PDT and immunotherapy against tumor metastasis and tumor recurrence may be improved by combination strategies. In this review, we discussed the possibility that PDT could be used to activate immune responses by inducing immunogenic cell death or generating cancer vaccines. Furthermore, we explored the latest advances in PDT antitumor therapy in combination with some immunotherapy such as immune adjuvants, inhibitors of immune suppression, and immune checkpoint blockade.