|
1
|
Sivashanmugan K, Reece EA, Lakowicz JR. On the Possibility of Fluorescent Capture Immunoassays on a Contact Lens. BIOSENSORS 2025; 15:326. [PMID: 40422065 PMCID: PMC12110756 DOI: 10.3390/bios15050326] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/09/2025] [Revised: 05/08/2025] [Accepted: 05/19/2025] [Indexed: 05/28/2025]
Abstract
Blood samples and testing are routine in healthcare. Presently, there is a growing interest in using tear samples in place of blood. Tear samples can be obtained non-invasively and collection does not require the skills of a trained phlebotomist. Red blood cells and other cells are not present in tears, which avoids centrifugation. Importantly, basal tear samples contain most of the biomarkers present in blood. The difficulty is the small volume of basal tears, which is about 7 μL in each eye. Any contact with the eye results in additional reflex tears with a different chemical composition. The small tear samples are collected with capillary tubes and then sent out for amplified assays, such as enzyme-linked immunosorbent assay (ELISA) or polymerase chain reaction (PCR). The results are not available for several days or a week and, therefore, are less useful in an ophthalmology office. We propose the use of a contact lens that contains bound antibodies for fluorescence immunoassays. The lenses could be removed from the patient for point-of-care measurements at the bedside. To prove that this concept is possible, we performed a three-layer protein capture assay that mimics an immunoassay. For convenience, we used lysozyme (Lys), which spontaneously coats silicon hydrogel (SiHG) contact lenses (CL). Anti-lysozyme IgG was the second layer captured, with anti-lysozyme considered to be the target biomarker. The third layer was rhodamine or Alexa Fluor-labeled Ab against the IgG Fc region, considered to be the detection antibody. The multiple protein layers were stable and did not wash off the SiHG lenses. These results strongly suggest the contact lens can be used for capture immunoassays for a wide variety of biomarkers.
Collapse
Affiliation(s)
- Kundan Sivashanmugan
- Center for Fluorescence Spectroscopy, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 721 West Lombard St., Baltimore, MD 21201, USA;
| | - E. Albert Reece
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, 655 W., Baltimore, MD 21201, USA;
| | - Joseph R. Lakowicz
- Center for Fluorescence Spectroscopy, Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 721 West Lombard St., Baltimore, MD 21201, USA;
| |
Collapse
|
|
2
|
Wang M, Zhu C, Feng N, Li Y, Sun J, Ju H. MALDI-TOF mass spectrometric immunoassay of multiple tumor biomarkers for non-small cell lung cancer screening. Talanta 2025; 286:127550. [PMID: 39799886 DOI: 10.1016/j.talanta.2025.127550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 12/29/2024] [Accepted: 01/04/2025] [Indexed: 01/15/2025]
Abstract
Cancer biomarkers have been facing some issues such as poor accuracy and low sensitivity in the early diagnosis of tumors. Utilizing biotin-labelled peptide as a mass tag (MT), this work proposes a high-throughput biosensing strategy for matrix-assisted laser desorption/ionization-time of flight mass spectrometric (MALDI-TOF-MS) immunoassay of multiple lung cancer biomarkers. Due to little required dosage, satisfied stability, high sensitivity and accuracy, this method can achieve off-site centralized signal detection after on-site sample incubation. The proposed approach has been successfully applied for the detection of carcinoembryonic antigen (CEA), carbohydrate antigen199 (CA199), carbohydrate antigen 125 (CA125) and cytokeratin-19-fragment (CY211) in serum samples from various stages of non-small cell lung cancer. Based on the analysis of multiple parameters and pathological results, significant differences in biomarkers are found in serum samples of lung cancer patients at different stages. More importantly, the analysis of multiple tumor biomarkers can improve the accuracy and sensitivity of early diagnosis. Therefore, the multiple immunoassay based on MALDI-TOF MS exhibits exceptional performance in terms of high throughput, little sample dosage, stability and sensitivity.
Collapse
Affiliation(s)
- Mengchen Wang
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China
| | - Chengxiang Zhu
- Nanjing Hospital of Traditional Chinese Medicine, Nanjing, 210022, China
| | - Nan Feng
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China
| | - Yiran Li
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China
| | - Jiahui Sun
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China
| | - Huangxian Ju
- State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.
| |
Collapse
|
|
3
|
Wang G, Sun Y, Liu C, Li Z. Immuno-transcription-amplified single microbead assay for protein and exosome analysis through an S9.6 antibody-nucleic acid recognition strategy. Biosens Bioelectron 2025; 271:117043. [PMID: 39657553 DOI: 10.1016/j.bios.2024.117043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 12/02/2024] [Accepted: 12/05/2024] [Indexed: 12/12/2024]
Abstract
High-sensitive detection of circulating biomarkers is in high demand because many of them are found at low concentrations in bioliquids. Herein, we report an immuno-transcription-amplified single microbead (MB) assay (IT-SMA) based on the specific S9.6 antibody-DNA/RNA hybrid recognition strategy for the sensitive and universal quantification of protein biomarkers. This design rationally converts the immunoreaction events into amplified nucleic acid transcription to produce numerous RNA molecules, which can efficiently enrich fluorescent signals onto a single MB through a specific S9.6 antibody-DNA/RNA hybrid recognition mechanism, enabling sensitive protein analysis. This method exhibits excellent specificity and high sensitivity for protein analysis with a low detection limit at the fg/mL level. Furthermore, the S9.6 antibody-aided IT-SMA allows for universal detection of various proteins and even exosomes, testing target proteins in serum samples, and differentiating cancer patients from healthy individuals by directly analyzing the exosomes in human blood samples. These features make the IT-SMA strategy a promising tool for the quantitative detection of a variety of biomarkers toward precision diagnostics.
Collapse
Affiliation(s)
- Gaoting Wang
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, 30 Xueyuan Road, Haidian District, Beijing, 100083, PR China
| | - Yuanyuan Sun
- Department of Translational Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450052, PR China
| | - Chenghui Liu
- Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry & Chemical Engineering, Shaanxi Normal University, Xi'an, Shaanxi Province, 710119, PR China.
| | - Zhengping Li
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, 30 Xueyuan Road, Haidian District, Beijing, 100083, PR China.
| |
Collapse
|
|
4
|
Joshi R, Ahmadi H, Gardner K, Bright RK, Wang W, Li W. Advances in microfluidic platforms for tumor cell phenotyping: from bench to bedside. LAB ON A CHIP 2025; 25:856-883. [PMID: 39774602 PMCID: PMC11859771 DOI: 10.1039/d4lc00403e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
Heterogeneities among tumor cells significantly contribute towards cancer progression and therapeutic inefficiency. Hence, understanding the nature of cancer through liquid biopsies and isolation of circulating tumor cells (CTCs) has gained considerable interest over the years. Microfluidics has emerged as one of the most popular platforms for performing liquid biopsy applications. Various label-free and labeling techniques using microfluidic platforms have been developed, the majority of which focus on CTC isolation from normal blood cells. However, sorting and profiling of various cell phenotypes present amongst those CTCs is equally important for prognostics and development of personalized therapies. In this review, firstly, we discuss the biophysical and biochemical heterogeneities associated with tumor cells and CTCs which contribute to cancer progression. Moreover, we discuss the recently developed microfluidic platforms for sorting and profiling of tumor cells and CTCs. These techniques are broadly classified into biophysical and biochemical phenotyping methods. Biophysical methods are further classified into mechanical and electrical phenotyping. While biochemical techniques have been categorized into surface antigen expressions, metabolism, and chemotaxis-based phenotyping methods. We also shed light on clinical studies performed with these platforms over the years and conclude with an outlook for the future development in this field.
Collapse
Affiliation(s)
- Rutwik Joshi
- Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
| | - Hesaneh Ahmadi
- Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
| | - Karl Gardner
- Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
| | - Robert K Bright
- Department of Immunology & Molecular Microbiology, School of Medicine & Cancer Center, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA
| | - Wenwen Wang
- Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Wei Li
- Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
| |
Collapse
|
|
5
|
Hsiao WWW, Pham UK, Le TN, Lam XM, Chiang WH. Advances in aggregation-induced emission luminogens for biomedicine: From luminescence mechanisms to diagnostic applications. Biosens Bioelectron 2025; 270:116942. [PMID: 39566330 DOI: 10.1016/j.bios.2024.116942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 10/26/2024] [Accepted: 11/12/2024] [Indexed: 11/22/2024]
Abstract
Advancements in early detection have demonstrated the significance of biomarkers as indicators of health and disease. Traditional detection methods often face limitations, such as low sensitivity and time consumption. Fluorescence-based techniques are considered promising approaches because of their noninvasiveness and rapid response. However, these conventional methods have some drawbacks, such as low quantum yield, photobleaching, and aggregation-caused quenching. Recently, aggregation-induced emission (AIE) has emerged as a potential alternative, characterized by luminous emission upon aggregation, thus improving detection sensitivity and stability. This review explores the recent advancements in AIE luminogens (AIEgens) in biomedical engineering, with a particular focus on their application in biomarker detection. Here, we discuss the different types of AIE mechanisms and their advantages in disease diagnosis and imaging. In addition, we summarize the development of various AIEgen-based probes for the detection of diverse biomarkers. Finally, we address the remaining challenges and future directions for AIE materials in modern biomedical engineering, emphasizing the potential of AIEgens in biomarker detection and disease diagnosis strategies.
Collapse
Affiliation(s)
- Wesley Wei-Wen Hsiao
- Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, 106335, Taiwan.
| | - Uyen Khanh Pham
- Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, 106335, Taiwan
| | - Trong-Nghia Le
- Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, 106319, Taiwan
| | - Xuan Mai Lam
- Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, 106335, Taiwan
| | - Wei-Hung Chiang
- Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, 106335, Taiwan; Sustainable Electrochemical Energy Development (SEED) Center, National Taiwan University of Science and Technology, Taipei City, 106335, Taiwan
| |
Collapse
|
|
6
|
Nemati SS, Dehghan G. Photoelectrochemical biosensors: Prospects of graphite carbon nitride-based sensors in prostate-specific antigen diagnosis. Anal Biochem 2025; 696:115686. [PMID: 39393750 DOI: 10.1016/j.ab.2024.115686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 10/07/2024] [Accepted: 10/07/2024] [Indexed: 10/13/2024]
Abstract
Prostate cancer (PC) is very common in old age and causes many deaths. Early diagnosis and monitoring of the progress of the disease and the effectiveness of PC treatment are critical. On the other hand, choosing a specific biomarker for PCs is essential. Prostate-specific antigen (PSA) is a specific biomarker secreted in the prostate epithelial cells, which increases in cancer cells. Between all employed sensing mechanism, electrochemical sensors based on nanomaterials have created many hopes. Meanwhile, graphite carbon nitride (g-C3N4) is interested in developing photoelectrochemical sensors due to its large surface area, stability, easy modification, and good photoelectronic properties. In this review, electrochemical sensors based on nanocomposites containing g-C3N4 have been investigated in PSA detection. After providing an overview of the characteristics of g-C3N4 and cancer biomarkers, it reviews the strategies and mechanisms involved in identifying PSA. Different approaches to photoelectrochemistry, impedimetric immunosensors, photocatalysis, and luminescence have been used in diagnostic mechanisms. Then, challenges and prospects for electrochemical sensors based on nanocomposites containing g-C3N4 in PSA detection have been analyzed. The recent review generally opens an efficient view in PSA diagnosis and the application of g-C3N4-based electrochemical sensors in personalized medicine diagnosis and treatment.
Collapse
Affiliation(s)
- Seyed Saman Nemati
- Laboratory of Biochemistry and Molecular Biology, Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran.
| | - Gholamreza Dehghan
- Laboratory of Biochemistry and Molecular Biology, Department of Biology, Faculty of Natural Science, University of Tabriz, Tabriz, Iran.
| |
Collapse
|
|
7
|
Cao Y, Xia J, Li L, Zeng Y, Zhao J, Li G. Electrochemical Biosensors for Cancer Diagnosis: Multitarget Analysis to Present Molecular Characteristics of Tumor Heterogeneity. JACS AU 2024; 4:4655-4672. [PMID: 39735934 PMCID: PMC11672140 DOI: 10.1021/jacsau.4c00989] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 11/26/2024] [Accepted: 12/02/2024] [Indexed: 12/31/2024]
Abstract
Electrochemical biosensors are gaining attention as powerful tools in cancer diagnosis, particularly in liquid biopsy, due to their high efficiency, rapid response, exceptional sensitivity, and specificity. However, the complexity of intra- and intertumor heterogeneity, with variations in genetic and protein expression profiles and epigenetic modifications, makes electrochemical biosensors susceptible to false-positive or false-negative diagnostic outcomes. To address this challenge, there is growing interest in simultaneously analyzing multiple biomarkers to reveal molecular characteristics of tumor heterogeneity for precise cancer diagnosis. In this Perspective, we highlight recent advancements in utilizing electrochemical biosensors for cancer diagnosis, with a specific emphasis on the multitarget analysis of cancer biomarkers including tumor-associated nucleic acids, tumor protein markers, extracellular vesicles, and tumor cells. These biosensors hold significant promise for improving precision in early cancer diagnosis and monitoring, as well as potentially offering new insights into personalized cancer management.
Collapse
Affiliation(s)
- Ya Cao
- Center
for Molecular Recognition and Biosensing, Shanghai Engineering Research
Center of Organ Repair, Joint International Research Laboratory of
Biomaterials and Biotechnology in Organ Repair (Ministry of Education),
School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Jianan Xia
- Center
for Molecular Recognition and Biosensing, Shanghai Engineering Research
Center of Organ Repair, Joint International Research Laboratory of
Biomaterials and Biotechnology in Organ Repair (Ministry of Education),
School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Lijuan Li
- Center
for Molecular Recognition and Biosensing, Shanghai Engineering Research
Center of Organ Repair, Joint International Research Laboratory of
Biomaterials and Biotechnology in Organ Repair (Ministry of Education),
School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Yujing Zeng
- State
Key Laboratory of Analytical Chemistry for Life Science, School of
Life Sciences, Nanjing University, Nanjing 210023, China
| | - Jing Zhao
- Center
for Molecular Recognition and Biosensing, Shanghai Engineering Research
Center of Organ Repair, Joint International Research Laboratory of
Biomaterials and Biotechnology in Organ Repair (Ministry of Education),
School of Life Sciences, Shanghai University, Shanghai 200444, China
| | - Genxi Li
- Center
for Molecular Recognition and Biosensing, Shanghai Engineering Research
Center of Organ Repair, Joint International Research Laboratory of
Biomaterials and Biotechnology in Organ Repair (Ministry of Education),
School of Life Sciences, Shanghai University, Shanghai 200444, China
- State
Key Laboratory of Analytical Chemistry for Life Science, School of
Life Sciences, Nanjing University, Nanjing 210023, China
| |
Collapse
|
|
8
|
Khaliq NU, Amin L, Khaliq SU, Amin A, Omer S, Khaliq IU, Kim Y, Kim J, Kim T, Seo D, Sung D, Kim H. Peptide-Based Prodrug Approaches for Cancer Nanomedicine. ACS APPLIED BIO MATERIALS 2024; 7:8163-8176. [PMID: 39601471 DOI: 10.1021/acsabm.4c01364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
Peptide-based prodrugs, such as peptide-drug conjugates (PDCs), are currently being developed for cancer therapy. PDCs are considered single-component nanomedicines with various functionalities. The peptide moieties provide stability to the PDCs, which self-assemble into nanostructures in an aqueous medium. Several PDCs based on peptide moieties have been developed for targeted cancer therapy, prevention of multidrug resistance (MDR), and theranostic applications. Based on this information, next-level strategies have been developed to deliver therapeutics and diagnostics to tumor tissues. The induction of apoptosis-targeted therapy is a conceptual approach that has evolved. In this context, smart PDCs have been designed and explored to overcome tumor heterogeneity. This review highlights strategies for the targeted delivery of small molecules and theranostic applications. Moreover, a conceptual approach to induce apoptosis-targeted therapy was exploited through the delivery of smart PDC nanomedicines and their composites.
Collapse
Affiliation(s)
- Nisar Ul Khaliq
- Department of Chemistry and Bioscience, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi 39177, Gyeongbuk Korea
| | - Laraib Amin
- Northwest General Hospital and Research Center, Peshawar 25100, Pakistan
| | - Saad Ul Khaliq
- Northwest General Hospital and Research Center, Peshawar 25100, Pakistan
| | - Anam Amin
- Northwest General Hospital and Research Center, Peshawar 25100, Pakistan
| | - Samreen Omer
- Riphah International University, Islamabad 44000, Pakistan
| | | | - Yejin Kim
- Department of Chemistry and Bioscience, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi 39177, Gyeongbuk Korea
| | - Joohyeon Kim
- Department of Chemistry and Bioscience, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi 39177, Gyeongbuk Korea
| | - Taeho Kim
- Department of Chemistry and Bioscience, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi 39177, Gyeongbuk Korea
| | - Dongseong Seo
- Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, Republic of Korea
- Center for Bio-Healthcare Materials, Bio-Convergence Materials R&D Division, Korea Institute of Ceramic 5 Engineering and Technology, 202 Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea
| | - Daekyung Sung
- Center for Bio-Healthcare Materials, Bio-Convergence Materials R&D Division, Korea Institute of Ceramic 5 Engineering and Technology, 202 Osongsaengmyeong 1-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 28160, Republic of Korea
| | - Hyungjun Kim
- Department of Chemistry and Bioscience, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi 39177, Gyeongbuk Korea
| |
Collapse
|
|
9
|
Shabbir A, Rashid MU, Awad EM, Naeemi H, Barisani-Asenbauer T, Malkani N. Association between the variations in metabolic pathways and oral cancer risk: results from a Pakistani case-control study. Mol Biol Rep 2024; 51:1165. [PMID: 39560804 DOI: 10.1007/s11033-024-10100-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 11/08/2024] [Indexed: 11/20/2024]
Abstract
BACKGROUND Oral cancer (OC) is a significant global health concern, with Pakistan ranking 5th worldwide in OC incidence. Given the poor prognosis, early detection of at-risk individuals is crucial. Genetic factors, particularly single nucleotide polymorphisms (SNPs) in metabolic genes, may influence OC susceptibility. This study investigated the association between SNPs in CYP1A1, COX2, SOD2, and HIF1a genes and OC risk in the Pakistani population. METHODS A prospective study was conducted from October 2019 to March 2022, enrolling 215 newly diagnosed OC patients and 410 controls. Genetic variations were analyzed using High-Resolution Melting (HRM) analysis and Sanger sequencing, with protein expression evaluated by ELISA. RESULTS No significant associations were found between the studied SNPs and OC risk. However, a non-significant trend was observed for the SOD2 variant (rs4880), where the G allele was associated with a higher OC risk than the A allele (p = 0.20). Elevated COX2 and HIF1α levels (p-values of 0.014 and < 0.001, respectively) and reduced SOD2 levels (p < 0.0001) were observed in OC patients, while CYP1A1 levels remained similar in both controls and cases. CONCLUSION Although SNPs in CYP1A1, COX2, SOD2, and HIF1α were not significantly associated with OC risk in the Pakistani population, altered protein expression levels of COX2, HIF1α and SOD2 suggest additional regulatory mechanisms. Further investigation into post-transcriptional modifications and epigenetic factors could lead to novel biomarkers and therapeutic targets for OC in Pakistan.
Collapse
Affiliation(s)
- Arifa Shabbir
- Department of Zoology, GC University, Lahore, Pakistan
| | - Muhammad Usman Rashid
- Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC), Lahore, Pakistan
| | - Ezzat M Awad
- Department of Ophthalmology & Optometry, Medical University Vienna, Vienna, Austria
| | - Humaira Naeemi
- Department of Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC), Lahore, Pakistan
| | | | - Naila Malkani
- Department of Zoology, GC University, Lahore, Pakistan.
| |
Collapse
|
|
10
|
Su Y, Zhou L. Review of single-molecule immunoassays: Non-chip and on-chip Assays. Anal Chim Acta 2024; 1322:342885. [PMID: 39182983 DOI: 10.1016/j.aca.2024.342885] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 06/17/2024] [Accepted: 06/17/2024] [Indexed: 08/27/2024]
Abstract
Enhancing the sensitivity of immunoassays is an important requirement in the field of immunology, especially in light of rapid developments in genetic testing, making the detection of low-abundance protein biomarkers crucial. Therefore, innovations in highly sensitive immunoassays are imperative. This demand has led to the emergence of single-molecule immunoassays (SMIs), driving advancements in early diagnostic techniques, and ushering in a new era of immunoassays. This review begins by tracing the development of immunoassays and offers a detailed discussion of SMI technology across two distinct pathways: non-chip (SMI without microfluidic chips) and on-chip (SMI with microfluidic chips). Furthermore, we evaluated and compared these methods using two pathways. In addition, this review discusses the significance of SMI techniques in the diagnosis of various diseases and their current applications in laboratory and clinical settings. The progress of SMI in commercial applications and suggestions for innovative directions are also summarized. Despite the considerable potential of SMI, these technologies face challenges in practical application, particularly in developing countries and economically disadvantaged regions. The final section of this review addresses the challenges and prospects of these technologies.
Collapse
Affiliation(s)
- Yan Su
- State Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China; Key Laboratory of Biopharmaceutical Preparation and Delivery, Chinese Academy of Sciences, Beijing, 100190, China
| | - Lei Zhou
- State Key Laboratory of Biochemical Engineering, PLA Key Laboratory of Biopharmaceutical Production & Formulation Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, China; Key Laboratory of Biopharmaceutical Preparation and Delivery, Chinese Academy of Sciences, Beijing, 100190, China; University of Chinese Academy of Sciences, Beijing, 100049, China; Innovation Academy for Green Manufacture Institute, Chinese Academy of Sciences, Beijing, 100190, China; Biosafety Research Center Yangtze River Delta in Zhangjiagang, Suzhou, 215611, China.
| |
Collapse
|
|
11
|
Quezada C, Samhitha SS, Salas A, Ges A, Barraza LF, Blanco-López MC, Solís-Pomar F, Pérez-Tijerina E, Medina C, Meléndrez M. Sensors Based on Molecularly Imprinted Polymers in the Field of Cancer Biomarker Detection: A Review. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 14:1361. [PMID: 39195399 DOI: 10.3390/nano14161361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 07/02/2024] [Accepted: 07/15/2024] [Indexed: 08/29/2024]
Abstract
Biomarkers play a pivotal role in the screening, diagnosis, prevention, and post-treatment follow-up of various malignant tumors. In certain instances, identifying these markers necessitates prior treatment due to the complex nature of the tumor microenvironment. Consequently, advancing techniques that exhibit selectivity, specificity, and enable streamlined analysis hold significant importance. Molecularly imprinted polymers (MIPs) are considered synthetic antibodies because they possess the property of molecular recognition with high selectivity and sensitivity. In recent years, there has been a notable surge in the investigation of these materials, primarily driven by their remarkable adaptability in terms of tailoring them for specific target molecules and integrating them into diverse analytical technologies. This review presents a comprehensive analysis of molecular imprinting techniques, highlighting their application in developing sensors and analytical methods for cancer detection, diagnosis, and monitoring. Therefore, MIPs offer great potential in oncology and show promise for improving the accuracy of cancer screening and diagnosis procedures.
Collapse
Affiliation(s)
- Camila Quezada
- Department of Materials Engineering (DIMAT), Faculty of Engineering, Universidad de Concepción, Edmundo Larenas 315, Box 160-C, Concepción 4070409, Chile
| | - S Shiva Samhitha
- Department of Materials Engineering (DIMAT), Faculty of Engineering, Universidad de Concepción, Edmundo Larenas 315, Box 160-C, Concepción 4070409, Chile
| | - Alexis Salas
- Department of Mechanical Engineering (DIM), Faculty of Engineering, University of Concepción, 219 Edmundo Larenas, Concepción 4070409, Chile
| | - Adrián Ges
- Department of Materials Engineering (DIMAT), Faculty of Engineering, Universidad de Concepción, Edmundo Larenas 315, Box 160-C, Concepción 4070409, Chile
| | - Luis F Barraza
- Department of Biological and Chemical Sciences, Faculty of Medicine and Science, Universidad San Sebastián, General Lagos 1163, Valdivia 5090000, Chile
| | - María Carmen Blanco-López
- Department of Physical and Analytical Chemistry, Asturias Biotechnology Institute, University of Oviedo, 33006 Oviedo, Spain
| | - Francisco Solís-Pomar
- Centro de Investigación en Ciencias Físico Matemáticas, Facultad de Ciencias Físico Matemáticas, Universidad Autónoma de Nuevo León, Av. Universidad s/n, San Nicolás de Los Garza 66455, Mexico
| | - Eduardo Pérez-Tijerina
- Centro de Investigación en Ciencias Físico Matemáticas, Facultad de Ciencias Físico Matemáticas, Universidad Autónoma de Nuevo León, Av. Universidad s/n, San Nicolás de Los Garza 66455, Mexico
| | - Carlos Medina
- Department of Mechanical Engineering (DIM), Faculty of Engineering, University of Concepción, 219 Edmundo Larenas, Concepción 4070409, Chile
| | - Manuel Meléndrez
- Facultad de Ciencias para el Cuidado de la Salud, Universidad San Sebastián, Campus Las Tres Pascualas, Lientur 1457, Concepción 4060000, Chile
| |
Collapse
|
|
12
|
Pandya K, Jagani D, Singh N. CRISPR-Cas Systems: Programmable Nuclease Revolutionizing the Molecular Diagnosis. Mol Biotechnol 2024; 66:1739-1753. [PMID: 37466850 DOI: 10.1007/s12033-023-00819-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Accepted: 07/06/2023] [Indexed: 07/20/2023]
Abstract
CRISPR-Cas system has evolved as a highly preferred genetic engineering tool to perform target gene manipulation via alteration of the guide RNA (gRNA) sequence. The ability to recognize and cleave a specific target with high precision has led to its applicability in multiple frontiers pertaining to human health and medicine. From basic research focused on understanding the molecular basis of disease to translational approach leading to early and precise disease diagnosis as well as developing effective therapeutics, the CRISPR-Cas system has proved to be a quite versatile tool. The coupling of CRISPR-Cas mediated cleavage with isothermal amplification (ISA) of target DNA, followed by a read-out using fluorescent or colorimetric reporters appears quite promising in providing a solution to the urgent need for nucleic acid-based point-of-care diagnostic. Hence, it has been recognized as a highly sophisticated molecular diagnostic tool for the detection of disease-specific biomarkers not limited to nucleic acids-based detection but also of non-nucleic acid targets such as proteins, exosomes, and other small molecules. In this review, we have presented salient features and principles of class 2 type II, V, and VI CRISPR-Cas systems represented by Cas9, Cas12, and Cas13 endonucleases which are frequently used in molecular diagnosis. The article then highlights different medical diagnostic applications of CRISPR-Cas systems focusing on the diagnosis of SARS-CoV-2, Dengue, Mycobacterium tuberculosis, and Listeria monocytogenes. Lastly, we discuss existing obstacles and potential future pathways concerning this subject in a concise manner.
Collapse
Affiliation(s)
- Kavya Pandya
- Department of Biotechnology and Bioengineering, Institute of Advanced Research, Gandhinagar, India
| | - Deep Jagani
- Department of Biotechnology and Bioengineering, Institute of Advanced Research, Gandhinagar, India
| | - Neeru Singh
- Department of Biotechnology and Bioengineering, Institute of Advanced Research, Gandhinagar, India.
| |
Collapse
|
|
13
|
Gao F, Ye S, Huang L, Gu Z. A nanoparticle-assisted signal-enhancement technique for lateral flow immunoassays. J Mater Chem B 2024; 12:6735-6756. [PMID: 38920348 DOI: 10.1039/d4tb00865k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/27/2024]
Abstract
Lateral flow immunoassay (LFIA), an affordable and rapid paper-based detection technology, is employed extensively in clinical diagnosis, environmental monitoring, and food safety analysis. The COVID-19 pandemic underscored the validity and adoption of LFIA in performing large-scale clinical and public health testing. The unprecedented demand for prompt diagnostic responses and advances in nanotechnology have fueled the rise of next-generation LFIA technologies. The utilization of nanoparticles to amplify signals represents an innovative approach aimed at augmenting LFIA sensitivity. This review probes the nanoparticle-assisted amplification strategies in LFIA applications to secure low detection limits and expedited response rates. Emphasis is placed on comprehending the correlation between the physicochemical properties of nanoparticles and LFIA performance. Lastly, we shed light on the challenges and opportunities in this prolific field.
Collapse
Affiliation(s)
- Fang Gao
- Institute of Energy Materials Science, University of Shanghai for Science and Technology, Shanghai 200093, P. R. China
| | - Shaonian Ye
- Institute of Energy Materials Science, University of Shanghai for Science and Technology, Shanghai 200093, P. R. China
| | - Lin Huang
- Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
- Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China
| | - Zhengying Gu
- Department of Clinical Laboratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
- Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China
| |
Collapse
|
|
14
|
Meng X, Pang X, Yang J, Zhang X, Dong H. Recent Advances in Electrochemiluminescence Biosensors for MicroRNA Detection. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2307701. [PMID: 38152970 DOI: 10.1002/smll.202307701] [Citation(s) in RCA: 21] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 12/06/2023] [Indexed: 12/29/2023]
Abstract
Electrochemiluminescence (ECL) as an analytical technology with a perfect combination of electrochemistry and spectroscopy has received considerable attention in bioanalysis due to its high sensitivity and broad dynamic range. Given the selectivity of bio-recognition elements and the high sensitivity of the ECL analysis technique, ECL biosensors are powerful platforms for the sensitive detection of biomarkers, achieving the accurate prognosis and diagnosis of diseases. MicroRNAs (miRNAs) are crucial biomarkers involved in a variety of physiological and pathological processes, whose aberrant expression is often related to serious diseases, especially cancers. ECL biosensors can fulfill the highly sensitive and selective requirements for accurate miRNA detection, prompting this review. The ECL mechanisms are initially introduced and subsequently categorize the ECL biosensors for miRNA detection in terms of the quenching agents. Furthermore, the work highlights the signal amplification strategies for enhancing ECL signal to improve the sensitivity of miRNA detection and finally concludes by looking at the challenges and opportunities in ECL biosensors for miRNA detection.
Collapse
Affiliation(s)
- Xiangdan Meng
- Beijing Key Laboratory for Bioengineering and Sensing Technology Research Centre for Bioengineering and Sensing Technology School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 10083, P. R. China
| | - Xuejiao Pang
- Beijing Key Laboratory for Bioengineering and Sensing Technology Research Centre for Bioengineering and Sensing Technology School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 10083, P. R. China
| | - Junyan Yang
- School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, P. R. China
| | - Xueji Zhang
- Beijing Key Laboratory for Bioengineering and Sensing Technology Research Centre for Bioengineering and Sensing Technology School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 10083, P. R. China
- Marshall Laboratory of Biomedical Engineering, Precision Medicine and Health Research Institute, Shenzhen Key Laboratory for Nano-Biosensing Technology, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Guangdong, 518060, P. R. China
| | - Haifeng Dong
- Beijing Key Laboratory for Bioengineering and Sensing Technology Research Centre for Bioengineering and Sensing Technology School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 10083, P. R. China
- Marshall Laboratory of Biomedical Engineering, Precision Medicine and Health Research Institute, Shenzhen Key Laboratory for Nano-Biosensing Technology, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Guangdong, 518060, P. R. China
| |
Collapse
|
|
15
|
Xiang Y, Liu J, Chen J, Xiao M, Pei H, Li L. MoS 2-Based Sensor Array for Accurate Identification of Cancer Cells with Ensemble-Modified Aptamers. ACS APPLIED MATERIALS & INTERFACES 2024; 16:15861-15869. [PMID: 38508220 DOI: 10.1021/acsami.3c19159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/22/2024]
Abstract
In this work, we present an array-based chemical nose sensor that utilizes a set of ensemble-modified aptamer (EMAmer) probes to sense subtle physicochemical changes on the cell surface for cancer cell identification. The EMAmer probes are engineered by domain-selective incorporation of different types and/or copies of positively charged functional groups into DNA scaffolds, and their differential interactions with cancer cells can be transduced through competitive adsorption of fluorophore-labeled EMAmer probes loaded on MoS2 nanosheets. We demonstrate that this MoS2-EMAmer-based sensor array enables rapid and effective discrimination among six types of cancer cells and their mixtures with a concentration of 104 cells within 60 min, achieving a 94.4% accuracy in identifying blinded unknown cell samples. The established MoS2-EMAmer sensing platform is anticipated to show significant promise in the advancement of cancer diagnostics.
Collapse
Affiliation(s)
- Ying Xiang
- Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, East China Normal University, 500 Dongchuan Road, Shanghai 200241, P. R. China
| | - Jingjing Liu
- Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, East China Normal University, 500 Dongchuan Road, Shanghai 200241, P. R. China
| | - Jing Chen
- Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, East China Normal University, 500 Dongchuan Road, Shanghai 200241, P. R. China
| | - Mingshu Xiao
- Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, East China Normal University, 500 Dongchuan Road, Shanghai 200241, P. R. China
| | - Hao Pei
- Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, East China Normal University, 500 Dongchuan Road, Shanghai 200241, P. R. China
| | - Li Li
- Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, East China Normal University, 500 Dongchuan Road, Shanghai 200241, P. R. China
| |
Collapse
|
|
16
|
Jiang S, Chen Y, Liang J, Xiao H, Lin M, Cui X, Zhao S. An AgPd NP-based lateral flow immunoassay for simultaneous detection of glycocholic acid and alpha-fetoprotein. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2024; 16:1508-1514. [PMID: 38372146 DOI: 10.1039/d3ay02286b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/20/2024]
Abstract
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality globally, ranking third in cancer deaths. Early diagnosis of HCC markers is imperative for effective prognosis and treatment. This study explores the utility of glycocholic acid (GCA) and alpha-fetoprotein (AFP) as biomarkers for liver diseases, with a specific focus on their simultaneous detection for enhanced diagnostic and prognostic capabilities. Harnessing the benefits of lateral flow immunoassay (LFIA), such as operational simplicity, speed, and accuracy, we engineered AgPd nanocomposites with antibodies targeting GCA and AFP. Under the optimized conditions, the visual detection limit for GCA was established at 50 ng mL-1 and the cut-off value at 104 ng mL-1. And for AFP, the visual detection limit was 0.1 ng mL-1 and the cut-off value was 500 ng mL-1. The accuracy and feasibility of the strips were validated through the detection of 39 actual serum samples. The results highlight the potential of LFIA as a rapid and effective tool for clinical diagnosis. The developed LFIA method not only demonstrates accuracy and feasibility but also presents a promising avenue for the early diagnosis of hepatocellular carcinoma.
Collapse
Affiliation(s)
- Shilin Jiang
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
| | - Yaqiong Chen
- Department of Laboratory Medicine, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Jinhui Liang
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
| | - Huanxin Xiao
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
| | - Mingxia Lin
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
| | - Xiping Cui
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
| | - Suqing Zhao
- Department of Pharmaceutical Engineering, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, People's Republic of China.
| |
Collapse
|
|
17
|
Macchia E, Torricelli F, Caputo M, Sarcina L, Scandurra C, Bollella P, Catacchio M, Piscitelli M, Di Franco C, Scamarcio G, Torsi L. Point-Of-Care Ultra-Portable Single-Molecule Bioassays for One-Health. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2309705. [PMID: 38108547 DOI: 10.1002/adma.202309705] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 11/20/2023] [Indexed: 12/19/2023]
Abstract
Screening asymptomatic organisms (humans, animals, plants) with a high-diagnostic accuracy using point-of-care-testing (POCT) technologies, though still visionary holds great potential. Convenient surveillance requires easy-to-use, cost-effective, ultra-portable but highly reliable, in-vitro-diagnostic devices that are ready for use wherever they are needed. Currently, there are not yet such devices available on the market, but there are a couple more promising technologies developed at readiness-level 5: the Clustered-Regularly-Interspaced-Short-Palindromic-Repeats (CRISPR) lateral-flow-strip tests and the Single-Molecule-with-a-large-Transistor (SiMoT) bioelectronic palmar devices. They both hold key features delineated by the World-Health-Organization for POCT systems and an occurrence of false-positive and false-negative errors <1-5% resulting in diagnostic-selectivity and sensitivity >95-99%, while limit-of-detections are of few markers. CRISPR-strip is a molecular assay that, can detect down to few copies of DNA/RNA markers in blood while SiMoT immunometric and molecular test can detect down to a single oligonucleotide, protein marker, or pathogens in 0.1mL of blood, saliva, and olive-sap. These technologies can prospectively enable the systematic and reliable surveillance of asymptomatic ones prior to worsening/proliferation of illnesses allowing for timely diagnosis and swift prognosis. This could establish a proactive healthcare ecosystem that results in effective treatments for all living organisms generating diffuse and well-being at efficient costs.
Collapse
Affiliation(s)
- Eleonora Macchia
- Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Bari, 70125, Italy
| | - Fabrizio Torricelli
- Dipartimento Ingegneria dell'Informazione, Università degli Studi di Brescia, Brescia, 25123, Italy
| | - Mariapia Caputo
- Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Bari, 70125, Italy
| | - Lucia Sarcina
- Dipartimento di Chimica and Centre for Colloid and Surface Science, Università degli Studi di Bari Aldo Moro, Bari, 20125, Italy
| | - Cecilia Scandurra
- Dipartimento di Chimica and Centre for Colloid and Surface Science, Università degli Studi di Bari Aldo Moro, Bari, 20125, Italy
| | - Paolo Bollella
- Dipartimento di Chimica and Centre for Colloid and Surface Science, Università degli Studi di Bari Aldo Moro, Bari, 20125, Italy
| | - Michele Catacchio
- Dipartimento di Chimica and Centre for Colloid and Surface Science, Università degli Studi di Bari Aldo Moro, Bari, 20125, Italy
| | - Matteo Piscitelli
- Dipartimento Interateneo di Fisica, Università degli Studi di Bari Aldo Moro, Bari, 70125, Italy
- CNR IFN, Bari, 70126, Italy
| | | | - Gaetano Scamarcio
- Dipartimento Interateneo di Fisica, Università degli Studi di Bari Aldo Moro, Bari, 70125, Italy
- CNR IFN, Bari, 70126, Italy
| | - Luisa Torsi
- Dipartimento di Chimica and Centre for Colloid and Surface Science, Università degli Studi di Bari Aldo Moro, Bari, 20125, Italy
| |
Collapse
|
|
18
|
Jin Y, Huang Z, Xu B, Chen J. Localization of multiple DNAzymes as a branchedzyme-powered nanodevice for the immunoassay of tumor biomarkers. Anal Chim Acta 2023; 1274:341580. [PMID: 37455088 DOI: 10.1016/j.aca.2023.341580] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 06/28/2023] [Accepted: 06/29/2023] [Indexed: 07/18/2023]
Abstract
Traditional immunoassay methods often face challenges due to the labeling procedure of protein enzymes, the use of multiple antibodies, and severe conditions. To address these limitations, we propose the concept of incorporating branchedzyme-powered nanodevices into immunoassays. In this strategy, multiple DNAzymes are localized onto gold nanoparticles (AuNPs) along with substrates. The localization format facilitates intramolecular reactions between DNAzymes and substrates, leading to accelerated kinetics of the nanodevice. Upon the formation of an immunocomplex with an antibody on a 96-well plate, the branchedzyme-powered nanodevice catalytically releases multiple fluorescent signals under ambient temperature, eliminating the need for secondary antibodies. The branched DNAzymes exhibit catalytic properties similar to those of protein enzymes, thus simplifying the assay procedure and achieving isothermal detection. Furthermore, the detection process can be controlled by the addition or deletion of cofactors. Additionally, the affinity ligand can be easily modified to construct nanodevices specific to different targets without requiring extensive redesign. This strategy has demonstrated successful quantification of tumor biomarkers such as alpha-fetoprotein (AFP) and prostate-specific antigen (PSA) at subpicomolar concentrations, showcasing its suitability for clinical applications. Consequently, the branchedzyme-powered nanodevice represents a valuable addition to the immunoassay toolbox, opening new possibilities for clinical diagnostics.
Collapse
Affiliation(s)
- Yanwen Jin
- Division of Biliary Tract Surgery, Department of General Surgery, West China Hospital, Sichuan Universtity, Chengdu, Sichuan, 610064, China
| | - Zhuochun Huang
- Department of Laboratory Medicine, West China Hospital, Sichuan Universtity, Chengdu, Sichuan, 610064, China
| | - Bingyan Xu
- Department of Laboratory Medicine, West China Hospital, Sichuan Universtity, Chengdu, Sichuan, 610064, China
| | - Junbo Chen
- Analytical & Testing Centre, Sichuan University, Chengdu, Sichuan, 610064, China.
| |
Collapse
|
|
19
|
Davodabadi F, Mirinejad S, Fathi-Karkan S, Majidpour M, Ajalli N, Sheervalilou R, Sargazi S, Rozmus D, Rahdar A, Diez-Pascual AM. Aptamer-functionalized quantum dots as theranostic nanotools against cancer and bacterial infections: A comprehensive overview of recent trends. Biotechnol Prog 2023; 39:e3366. [PMID: 37222166 DOI: 10.1002/btpr.3366] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 04/21/2023] [Accepted: 05/09/2023] [Indexed: 05/25/2023]
Abstract
Aptamers (Apts) are synthetic nucleic acid ligands that can be engineered to target various molecules, including amino acids, proteins, and pharmaceuticals. Through a series of adsorption, recovery, and amplification steps, Apts are extracted from combinatorial libraries of synthesized nucleic acids. Using aptasensors in bioanalysis and biomedicine can be improved by combining them with nanomaterials. Moreover, Apt-associated nanomaterials, including liposomes, polymeric, dendrimers, carbon nanomaterials, silica, nanorods, magnetic NPs, and quantum dots (QDs), have been widely used as promising nanotools in biomedicine. Following surface modifications and conjugation with appropriate functional groups, these nanomaterials can be successfully used in aptasensing. Advanced biological assays can use Apts immobilized on QD surfaces through physical interaction and chemical bonding. Accordingly, modern QD aptasensing platforms rely on interactions between QDs, Apts, and targets to detect them. QD-Apt conjugates can be used to directly detect prostate, ovarian, colorectal, and lung cancers or simultaneously detect biomarkers associated with these malignancies. Tenascin-C, mucin 1, prostate-specific antigen, prostate-specific membrane antigen, nucleolin, growth factors, and exosomes are among the cancer biomarkers that can be sensitively detected using such bioconjugates. Furthermore, Apt-conjugated QDs have shown great potential for controlling bacterial infections such as Bacillus thuringiensis, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Campylobacter jejuni, Staphylococcus aureus, and Salmonella typhimurium. This comprehensive review discusses recent advancements in the design of QD-Apt bioconjugates and their applications in cancer and bacterial theranostics.
Collapse
Affiliation(s)
- Fatemeh Davodabadi
- Department of Biology, Faculty of Basic Science, Payame Noor University, Tehran, Iran
| | - Shekoufeh Mirinejad
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Sonia Fathi-Karkan
- Department of Advanced Sciences and Technologies in Medicine, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
| | - Mahdi Majidpour
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Narges Ajalli
- Department of Chemical Engineering, Faculty of Engineering, University of Tehran, Tehran, Iran
| | | | - Saman Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Dominika Rozmus
- Department of Biochemistry, Faculty of Biology and Biotechnology, University of Warmia and Mazury, Olsztyn, Poland
| | - Abbas Rahdar
- Department of Physics, University of Zabol, Zabol, Iran
| | - Ana M Diez-Pascual
- Universidad de Alcalá, Facultad de Ciencias, Departamento de Quimica Analitica, Quimica Fisica e Ingenieria Quimica, Madrid, Spain
| |
Collapse
|
|
20
|
Quansah M, Fetter L, Fineran A, Colling HV, Silver K, Rowland TJ, Bonham AJ. Rapid and Quantitative Detection of Lung Cancer Biomarker ENOX2 Using a Novel Aptamer in an Electrochemical DNA-Based (E-DNA) Biosensor. BIOSENSORS 2023; 13:675. [PMID: 37504074 PMCID: PMC10377175 DOI: 10.3390/bios13070675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 06/16/2023] [Accepted: 06/23/2023] [Indexed: 07/29/2023]
Abstract
To overcome early cancer detection challenges, diagnostic tools enabling more sensitive, rapid, and noninvasive detection are necessary. An attractive cancer target for diagnostic blood tests is human Ecto-NOX disulfide-thiol exchanger 2 (ENOX2), expressed in most human cancer types and regularly shed into blood sera. Here, we developed an electrochemical DNA-based (E-DNA) biosensor that rapidly detects physiologically relevant levels of ENOX2. To identify ENOX2-binding aptamers that could potentially be used in a biosensor, recombinantly expressed ENOX2 was used as a binding target in an oligonucleotide library pull-down that generated a highly enriched ENOX2-binding aptamer. This candidate aptamer sensitively bound ENOX2 via gel mobility shift assays. To enable this aptamer to function in an ENOX2 E-DNA biosensor, the aptamer sequence was modified to adopt two conformations, one capable of ENOX2 binding, and one with disrupted ENOX2 binding. Upon ENOX2 introduction, a conformational shift to the ENOX2 binding state resulted in changed dynamics of a redox reporter molecule, which generated a rapid, significant, and target-specific electrical current readout change. ENOX2 biosensor sensitivity was at or below the diagnostic range. The ENOX2 E-DNA biosensor design presented here may enable the development of more sensitive, rapid, diagnostic tools for early cancer detection.
Collapse
Affiliation(s)
- Mary Quansah
- Department of Chemistry & Biochemistry, Metropolitan State University of Denver, Denver, CO 80204, USA
| | - Lisa Fetter
- Program in Biomolecular Science and Engineering, University of California Santa Barbara, Santa Barbara, CA 93106, USA
| | - Autumn Fineran
- Department of Chemistry & Biochemistry, Metropolitan State University of Denver, Denver, CO 80204, USA
| | - Haley V Colling
- Department of Chemistry & Biochemistry, Metropolitan State University of Denver, Denver, CO 80204, USA
| | - Keaton Silver
- Department of Chemistry & Biochemistry, Metropolitan State University of Denver, Denver, CO 80204, USA
| | - Teisha J Rowland
- Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA
| | - Andrew J Bonham
- Department of Chemistry & Biochemistry, Metropolitan State University of Denver, Denver, CO 80204, USA
| |
Collapse
|
|
21
|
Ahmad A, Imran M, Ahsan H. Biomarkers as Biomedical Bioindicators: Approaches and Techniques for the Detection, Analysis, and Validation of Novel Biomarkers of Diseases. Pharmaceutics 2023; 15:1630. [PMID: 37376078 DOI: 10.3390/pharmaceutics15061630] [Citation(s) in RCA: 71] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 05/24/2023] [Accepted: 05/29/2023] [Indexed: 06/29/2023] Open
Abstract
A biomarker is any measurable biological moiety that can be assessed and measured as a potential index of either normal or abnormal pathophysiology or pharmacological responses to some treatment regimen. Every tissue in the body has a distinct biomolecular make-up, which is known as its biomarkers, which possess particular features, viz., the levels or activities (the ability of a gene or protein to carry out a particular body function) of a gene, protein, or other biomolecules. A biomarker refers to some feature that can be objectively quantified by various biochemical samples and evaluates the exposure of an organism to normal or pathological procedures or their response to some drug interventions. An in-depth and comprehensive realization of the significance of these biomarkers becomes quite important for the efficient diagnosis of diseases and for providing the appropriate directions in case of multiple drug choices being presently available, which can benefit any patient. Presently, advancements in omics technologies have opened up new possibilities to obtain novel biomarkers of different types, employing genomic strategies, epigenetics, metabolomics, transcriptomics, lipid-based analysis, protein studies, etc. Particular biomarkers for specific diseases, their prognostic capabilities, and responses to therapeutic paradigms have been applied for screening of various normal healthy, as well as diseased, tissue or serum samples, and act as appreciable tools in pharmacology and therapeutics, etc. In this review, we have summarized various biomarker types, their classification, and monitoring and detection methods and strategies. Various analytical techniques and approaches of biomarkers have also been described along with various clinically applicable biomarker sensing techniques which have been developed in the recent past. A section has also been dedicated to the latest trends in the formulation and designing of nanotechnology-based biomarker sensing and detection developments in this field.
Collapse
Affiliation(s)
- Anas Ahmad
- Julia McFarlane Diabetes Research Centre (JMDRC), Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Hotchkiss Brain Institute, Cumming School of Medicine, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 4N1, Canada
| | - Mohammad Imran
- Therapeutics Research Group, Frazer Institute, Faculty of Medicine, University of Queensland, Brisbane 4102, Australia
| | - Haseeb Ahsan
- Department of Biochemistry, Faculty of Dentistry, Jamia Millia Islamia, New Delhi 110025, India
| |
Collapse
|
|
22
|
Zeng R, Wang L, Zhang Y, Yang Y, Yang J, Qin Y. Exploring the immunological role and prognostic potential of PPM1M in pan-cancer. Medicine (Baltimore) 2023; 102:e32758. [PMID: 36961170 PMCID: PMC10036021 DOI: 10.1097/md.0000000000032758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Accepted: 01/05/2023] [Indexed: 03/25/2023] Open
Abstract
BACKGROUND PPM1M is a member of the metal-dependent protein phosphatase family, and its role in the immunization process has not been studied in depth. In this study, we investigated the role of PPM1M in pan-cancer. METHODS Samples of cancer and normal tissues were obtained from the cancer genome atlas and genotype-tissue expression. Kaplan-Meier survival curves and Cox regression were used to analyze the effect of PPM1M on prognosis. Functional and pathway enrichment analyses were performed using the R package "clusterProfiler" to explore the role of PPM1M. The Sanger Box database was used to analyze the relationship between PPM1M and tumor immune checkpoint, tumor mutational burden, and microsatellite instability. The Tumor Immune Estimation Resource 2 database and CIBERSORT method were used to analyze the relationship between PPM1M and tumor-infiltrating immune cells. Finally, the cBioPortal database was used to analyze the genomic variation in PPM1M. RESULTS Among the variety of tumors, the expression of PPM1M was higher in normal tissues than in cancerous tissues. The expression of PPM1M is closely associated with patient prognosis, tumor immune checkpoint, tumor mutational burden, and microsatellite instability. PPM1M is closely associated with the infiltration of immune cells into the tumor microenvironment. In addition, PPM1M is involved in the regulation of several immune-related pathways. CONCLUSION In pan-cancer, PPM1M affects patient prognosis and may be a potential immunological biomarker. Furthermore, PPM1M may be a potential therapeutic target in tumor immunology.
Collapse
Affiliation(s)
- Rongruo Zeng
- Department of Health Management, The People’s Hospital of Guangxi Zhuang Autonomous Region & Research Center of Health Management, Guangxi Academy of Medical Sciences, Nanning, Guangxi, People’s Republic of China
- Department of Pathology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China
| | - Lulu Wang
- Department of Health Management, The People’s Hospital of Guangxi Zhuang Autonomous Region & Research Center of Health Management, Guangxi Academy of Medical Sciences, Nanning, Guangxi, People’s Republic of China
| | - Yuxu Zhang
- Department of International Medicine Services, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of China
| | - Ye Yang
- Department of Rehabilitation Medicine, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China
| | - Jie Yang
- Department of Health Management, The People’s Hospital of Guangxi Zhuang Autonomous Region & Research Center of Health Management, Guangxi Academy of Medical Sciences, Nanning, Guangxi, People’s Republic of China
| | - Yan Qin
- Department of Health Management, The People’s Hospital of Guangxi Zhuang Autonomous Region & Research Center of Health Management, Guangxi Academy of Medical Sciences, Nanning, Guangxi, People’s Republic of China
| |
Collapse
|
|
23
|
Rafat N, Brewer L, Das N, Trivedi DJ, Kaszala BK, Sarkar A. Inexpensive High-Throughput Multiplexed Biomarker Detection Using Enzymatic Metallization with Cellphone-Based Computer Vision. ACS Sens 2023; 8:534-542. [PMID: 36753573 PMCID: PMC9972466 DOI: 10.1021/acssensors.2c01429] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
Abstract
Multiplexed biomarker detection can play a critical role in reliable and comprehensive disease diagnosis and prediction of outcome. Enzyme-linked immunosorbent assay (ELISA) is the gold standard method for immunobinding-based biomarker detection. However, this is currently expensive, limited to centralized laboratories, and usually limited to the detection of a single biomarker at a time. We present a low-cost, smartphone-based portable biosensing platform for high-throughput, multiplexed, sensitive, and quantitative detection of biomarkers from single, low-volume drops (<1 μL) of clinical samples. Biomarker binding to spotted capture antigens is converted, via enzymatic metallization, to the localized surface deposition of amplified, dry-stable, silver metal spots whose darkness is proportional to biomarker concentration. A custom smartphone application is developed, which uses real-time computer vision to enable easy optical detection of the deposited metal spots and sensitive and reproducible quantification of the biomarkers. We demonstrate the use of this platform for high-throughput, multiplexed detection of multiple viral antigen-specific antibodies from convalescent COVID-19 patient serum as well as vaccine-elicited antibody responses from uninfected vaccine-recipient serum and show that distinct multiplexed antibody fingerprints are observed among them.
Collapse
Affiliation(s)
- Neda Rafat
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
| | - Lee Brewer
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
| | - Nabojeet Das
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
| | - Dhruti J Trivedi
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
| | - Balazs K Kaszala
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
| | - Aniruddh Sarkar
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States
| |
Collapse
|
|
24
|
Paskeh MDA, Ghadyani F, Hashemi M, Abbaspour A, Zabolian A, Javanshir S, Razzazan M, Mirzaei S, Entezari M, Goharrizi MASB, Salimimoghadam S, Aref AR, Kalbasi A, Rajabi R, Rashidi M, Taheriazam A, Sethi G. Biological impact and therapeutic perspective of targeting PI3K/Akt signaling in hepatocellular carcinoma: Promises and Challenges. Pharmacol Res 2023; 187:106553. [PMID: 36400343 DOI: 10.1016/j.phrs.2022.106553] [Citation(s) in RCA: 73] [Impact Index Per Article: 36.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/09/2022] [Accepted: 11/10/2022] [Indexed: 11/17/2022]
Abstract
Cancer progression results from activation of various signaling networks. Among these, PI3K/Akt signaling contributes to proliferation, invasion, and inhibition of apoptosis. Hepatocellular carcinoma (HCC) is a primary liver cancer with high incidence rate, especially in regions with high prevalence of viral hepatitis infection. Autoimmune disorders, diabetes mellitus, obesity, alcohol consumption, and inflammation can also lead to initiation and development of HCC. The treatment of HCC depends on the identification of oncogenic factors that lead tumor cells to develop resistance to therapy. The present review article focuses on the role of PI3K/Akt signaling in HCC progression. Activation of PI3K/Akt signaling promotes glucose uptake, favors glycolysis and increases tumor cell proliferation. It inhibits both apoptosis and autophagy while promoting HCC cell survival. PI3K/Akt stimulates epithelial-to-mesenchymal transition (EMT) and increases matrix-metalloproteinase (MMP) expression during HCC metastasis. In addition to increasing colony formation capacity and facilitating the spread of tumor cells, PI3K/Akt signaling stimulates angiogenesis. Therefore, silencing PI3K/Akt signaling prevents aggressive HCC cell behavior. Activation of PI3K/Akt signaling can confer drug resistance, particularly to sorafenib, and decreases the radio-sensitivity of HCC cells. Anti-cancer agents, like phytochemicals and small molecules can suppress PI3K/Akt signaling by limiting HCC progression. Being upregulated in tumor tissues and clinical samples, PI3K/Akt can also be used as a biomarker to predict patients' response to therapy.
Collapse
Affiliation(s)
- Mahshid Deldar Abad Paskeh
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Fatemeh Ghadyani
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mehrdad Hashemi
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Alireza Abbaspour
- Cellular and Molecular Research Center,Qazvin University of Medical Sciences, Qazvin, Iran
| | - Amirhossein Zabolian
- Resident of department of Orthopedics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Salar Javanshir
- Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mehrnaz Razzazan
- Medical Student, Student Research Committee, Golestan University of Medical Sciences, Gorgan, Iran
| | - Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Maliheh Entezari
- Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | | | - Shokooh Salimimoghadam
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Amir Reza Aref
- Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Translational Sciences, Xsphera Biosciences Inc. 6, Tide Street, Boston, MA 02210, USA
| | - Alireza Kalbasi
- Department of Pharmacy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Romina Rajabi
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran.
| | - Mohsen Rashidi
- Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Afshin Taheriazam
- Farhikhtegan Medical Convergence sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
| |
Collapse
|
|
25
|
Xanthene dyes for cancer imaging and treatment: A material odyssey. Coord Chem Rev 2023. [DOI: 10.1016/j.ccr.2022.214841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
|
|
26
|
On the use of spectroscopy, prediction machines and cybernetics for an affordable and proactive care approach for endometrial cancer. BIOMEDICAL ENGINEERING ADVANCES 2022. [DOI: 10.1016/j.bea.2022.100057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
|
|
27
|
Pourmadadi M, Rajabzadeh-Khosroshahi M, Saeidi Tabar F, Ajalli N, Samadi A, Yazdani M, Yazdian F, Rahdar A, Díez-Pascual AM. Two-Dimensional Graphitic Carbon Nitride (g-C 3N 4) Nanosheets and Their Derivatives for Diagnosis and Detection Applications. J Funct Biomater 2022; 13:204. [PMID: 36412845 PMCID: PMC9680252 DOI: 10.3390/jfb13040204] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/21/2022] [Accepted: 10/23/2022] [Indexed: 12/14/2022] Open
Abstract
The early diagnosis of certain fatal diseases is vital for preventing severe consequences and contributes to a more effective treatment. Despite numerous conventional methods to realize this goal, employing nanobiosensors is a novel approach that provides a fast and precise detection. Recently, nanomaterials have been widely applied as biosensors with distinctive features. Graphite phase carbon nitride (g-C3N4) is a two-dimensional (2D) carbon-based nanostructure that has received attention in biosensing. Biocompatibility, biodegradability, semiconductivity, high photoluminescence yield, low-cost synthesis, easy production process, antimicrobial activity, and high stability are prominent properties that have rendered g-C3N4 a promising candidate to be used in electrochemical, optical, and other kinds of biosensors. This review presents the g-C3N4 unique features, synthesis methods, and g-C3N4-based nanomaterials. In addition, recent relevant studies on using g-C3N4 in biosensors in regard to improving treatment pathways are reviewed.
Collapse
Affiliation(s)
- Mehrab Pourmadadi
- School of Chemical Engineering, College of Engineering, University of Tehran, Tehran 14179-35840, Iran
| | | | - Fatemeh Saeidi Tabar
- School of Chemical Engineering, College of Engineering, University of Tehran, Tehran 14179-35840, Iran
| | - Narges Ajalli
- School of Chemical Engineering, College of Engineering, University of Tehran, Tehran 14179-35840, Iran
| | - Amirmasoud Samadi
- School of Chemical Engineering, College of Engineering, University of Tehran, Tehran 14179-35840, Iran
- Department of Chemical and Biomolecular Engineering, 6000 Interdisciplinary Science & Engineering Building (ISEB), Irvine, CA 92617, USA
| | - Mahsa Yazdani
- School of Chemical Engineering, College of Engineering, University of Tehran, Tehran 14179-35840, Iran
- Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY 14260, USA
| | - Fatemeh Yazdian
- Department of Life Science Engineering, Faculty of New Science and Technologies, University of Tehran, Tehran 14179-35840, Iran
| | - Abbas Rahdar
- Department of Physics, Faculty of science, University of Zabol, Zabol 538-98615, Iran
| | - Ana M. Díez-Pascual
- Universidad de Alcalá, Facultad de Ciencias, Departamento de Química Analítica, Química Física e Ingeniería Química, Ctra. Madrid-Barcelona, Km. 33.6, 28805 Alcalá de Henares, Madrid, Spain
| |
Collapse
|
|
28
|
Han H, Zhong Y, He C, Fu L, Huang Q, Kuang Y, Yi X, Zeng W, Zhong H, Yang M. Recent advances in organic fluorescent probes for tumor related enzyme detection. DYES AND PIGMENTS 2022; 204:110386. [DOI: 10.1016/j.dyepig.2022.110386] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
29
|
Wang Q, Han N, Shen Z, Li X, Chen Z, Cao Y, Si W, Wang F, Ni BJ, Thakur VK. MXene-based electrochemical (bio) sensors for sustainable applications: Roadmap for future advanced materials. NANO MATERIALS SCIENCE 2022. [DOI: 10.1016/j.nanoms.2022.07.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
|
|
30
|
Bölükbaşi ÖS, Yola BB, Karaman C, Atar N, Yola ML. Electrochemical α-fetoprotein immunosensor based on Fe 3O 4NPs@covalent organic framework decorated gold nanoparticles and magnetic nanoparticles including SiO 2@TiO 2. Mikrochim Acta 2022; 189:242. [PMID: 35654985 DOI: 10.1007/s00604-022-05344-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 05/15/2022] [Indexed: 01/09/2023]
Abstract
The early diagnosis of major diseases such as cancer is typically a major issue for humanity. Human α-fetoprotein (AFP) as a sialylated glycoprotein is of approximately 68 kD molecular weight and is considered to be a key biomarker, and an increase in its level indicates the presence of liver, testicular, or gastric cancer. In this study, an electrochemical AFP immunosensor based on Fe3O4NPs@covalent organic framework decorated gold nanoparticles (Fe3O4 NPs@COF/AuNPs) for the electrode platform and double-coated magnetic nanoparticles (MNPs) based on SiO2@TiO2 (MNPs@SiO2@TiO2) nanocomposites for the signal amplification was fabricated. The immobilization of anti-AFP capture antibody was successfully performed on Fe3O4 NPs@COF/AuNPs modified electrode surface by amino-gold affinity, while the conjugation of anti-AFP secondary antibody on MNPs@SiO2@TiO2 was achieved by the electrostatic/ionic interactions. Transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) analysis, cyclic voltammetry (CV), square wave voltammetry (SWV), and electrochemical impedance spectroscopy (EIS) techniques were used to characterize the nanostructures in terms of physical and electrochemical features. The limit of detection (LOD) was 3.30 fg mL-1. The findings revealed that the proposed electrochemical AFP immunosensor can be effectively used to diagnose cancer.
Collapse
Affiliation(s)
- Ömer Saltuk Bölükbaşi
- Department of Metallurgical and Materials Engineering, Faculty of Engineering and Natural Sciences, Iskenderun Technical University, Iskenderun, Hatay, Turkey
| | - Bahar Bankoğlu Yola
- Department of Engineering Basic Sciences, Faculty of Engineering and Natural Sciences, Gaziantep Islam Science and Technology University, Gaziantep, Turkey
| | - Ceren Karaman
- Department of Electricity and Energy, Vocational School of Technical Sciences, Akdeniz University, Antalya, Turkey
| | - Necip Atar
- Department of Chemical Engineering, Faculty of Engineering, Pamukkale University, Denizli, Turkey
| | - Mehmet Lütfi Yola
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Hasan Kalyoncu University, Gaziantep, Turkey.
| |
Collapse
|
|
31
|
Tang Q, Liu H, Qi J, Yan X, Mustafa A, Xi Y, Li J, Bai L, Liang L, Han C, Wang J. Mass spectrometry-based metabolic profiling for identification of biomarkers in serum related to the change of laying ducks in different physiological periods. ITALIAN JOURNAL OF ANIMAL SCIENCE 2022. [DOI: 10.1080/1828051x.2022.2063768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Qian Tang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Hehe Liu
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Jingjing Qi
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Xiping Yan
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Ahsan Mustafa
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Yang Xi
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Junpeng Li
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Lili Bai
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Li Liang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Chunchun Han
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Jiwen Wang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| |
Collapse
|
|
32
|
Parihar A, Singhal A, Kumar N, Khan R, Khan MA, Srivastava AK. Next-Generation Intelligent MXene-Based Electrochemical Aptasensors for Point-of-Care Cancer Diagnostics. NANO-MICRO LETTERS 2022; 14:100. [PMID: 35403935 PMCID: PMC8995416 DOI: 10.1007/s40820-022-00845-1] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 03/11/2022] [Indexed: 02/08/2023]
Abstract
Delayed diagnosis of cancer using conventional diagnostic modalities needs to be addressed to reduce the mortality rate of cancer. Recently, 2D nanomaterial-enabled advanced biosensors have shown potential towards the early diagnosis of cancer. The high surface area, surface functional groups availability, and excellent electrical conductivity of MXene make it the 2D material of choice for the fabrication of advanced electrochemical biosensors for disease diagnostics. MXene-enabled electrochemical aptasensors have shown great promise for the detection of cancer biomarkers with a femtomolar limit of detection. Additionally, the stability, ease of synthesis, good reproducibility, and high specificity offered by MXene-enabled aptasensors hold promise to be the mainstream diagnostic approach. In this review, the design and fabrication of MXene-based electrochemical aptasensors for the detection of cancer biomarkers have been discussed. Besides, various synthetic processes and useful properties of MXenes which can be tuned and optimized easily and efficiently to fabricate sensitive biosensors have been elucidated. Further, futuristic sensing applications along with challenges will be deliberated herein.
Collapse
Affiliation(s)
- Arpana Parihar
- Industrial Waste Utilization, Nano and Biomaterials, CSIR-Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, Bhopal, 462026, MP, India
| | - Ayushi Singhal
- Industrial Waste Utilization, Nano and Biomaterials, CSIR-Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, Bhopal, 462026, MP, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Neeraj Kumar
- Industrial Waste Utilization, Nano and Biomaterials, CSIR-Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, Bhopal, 462026, MP, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| | - Raju Khan
- Industrial Waste Utilization, Nano and Biomaterials, CSIR-Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, Bhopal, 462026, MP, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
| | - Mohd Akram Khan
- Industrial Waste Utilization, Nano and Biomaterials, CSIR-Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, Bhopal, 462026, MP, India
| | - Avanish K Srivastava
- Industrial Waste Utilization, Nano and Biomaterials, CSIR-Advanced Materials and Processes Research Institute (AMPRI), Hoshangabad Road, Bhopal, 462026, MP, India
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India
| |
Collapse
|
|
33
|
Chen D, Zhang X, Zhu L, Liu C, Li Z. All on size-coded single bead set: a modular enrich-amplify-amplify strategy for attomolar level multi-immunoassay. Chem Sci 2022; 13:3501-3506. [PMID: 35432875 PMCID: PMC8943839 DOI: 10.1039/d1sc07048g] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 02/17/2022] [Indexed: 12/04/2022] Open
Abstract
Ultrasensitive protein analysis is of great significance for early diagnosis and biological studies. The core challenge is that many critical protein markers at extremely low aM to fM levels are difficult to accurately quantify because the target-induced weak signal may be easily masked by the surrounding background. Hence, we propose herein an ultrasensitive immunoassay based on a modular Single Bead Enrich-Amplify-Amplify (SBEAA) strategy. The highly efficient enrichment of targets on only a single bead (enrich) could confine the target-responsive signal output within a limited tiny space. Furthermore, a cascade tyramide signal amplification design enables remarkable in situ signal enhancement just affixed to the target. As a result, the efficient but space-confined fluorescence deposition on a single bead will significantly exceed the background and provide a wide dynamic range. Importantly, the SBEAA system can be modularly combined to meet different levels of clinical need regarding the detection sensitivity from aM to nM. Finally, a size-coded SBEAA set (SC-SBEAA) is also designed that allows ultrasensitive multi-immunoassay for rare samples in a single tube.
Collapse
Affiliation(s)
- Desheng Chen
- Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University Xi'an 710119 Shaanxi Province P. R. China
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing 30 Xueyuan Road, Haidian District Beijing 100083 P. R. China
| | - Xiaobo Zhang
- Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University Xi'an 710119 Shaanxi Province P. R. China
| | - Liping Zhu
- Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University Xi'an 710119 Shaanxi Province P. R. China
| | - Chenghui Liu
- Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University Xi'an 710119 Shaanxi Province P. R. China
| | - Zhengping Li
- Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University Xi'an 710119 Shaanxi Province P. R. China
- Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing 30 Xueyuan Road, Haidian District Beijing 100083 P. R. China
| |
Collapse
|
|
34
|
Dual amplification enabled counting based ultrasensitive enzyme-linked immunosorbent assay. Anal Chim Acta 2022; 1198:339510. [DOI: 10.1016/j.aca.2022.339510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 01/12/2022] [Accepted: 01/14/2022] [Indexed: 11/17/2022]
|
|
35
|
Deng J, Xiao W, Wang Z. FAM46C as a Potential Marker for Pan-Cancer Prognosis and Predicting Immunotherapeutic Efficacy. Front Genet 2022; 13:810252. [PMID: 35222533 PMCID: PMC8864238 DOI: 10.3389/fgene.2022.810252] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 01/18/2022] [Indexed: 12/28/2022] Open
Abstract
Background:FAM46C is a common mutated gene in tumours. A comprehensive understanding of the relationship between FAM46C expression and pan-cancer can guide clinical prognosis and broaden the immunotherapeutic targets.Methods: Data from The Cancer Genome Atlas and Genotype-Tissue Expression (GTEx) databases were obtained, and gene expression of different tumour types and stages was analysed. Immunohistochemical analysis was performed to detect differences in the FAM46C protein levels in normal and cancerous tissues. The genetic variation of FAM46C was characterised using cBioPortal. The clinical prognostic value of FAM46C and the impact of FAM46C expression levels on the prognosis of patients with different types of cancer were assessed based on Kaplan–Meier and Cox regression analyses. Gene set enrichment analysis (GSEA) was used to analyse the pathways associated with FAM46C. Correlations between FAM46C expression levels and immune infiltration were assessed using the TIMER2 database and CIBERSORT algorithm, and correlations between FAM46C expression and the ESTIMATE, immune and stromal scores were analysed using the ESTIMATE algorithm. In addition, we also analysed the correlation between FAM46C expression and immune activation, suppression genes and immune chemokines.Results: The expression level of FAM46C was correlated with the prognosis of most tumours, and low expression levels often suggested a poor prognosis. FAM46C was positively correlated with the abundance of CD4+ T cells, CD8+ T cells and plasma B lymphocytes in the tumour microenvironment. FAM46C exhibited a strong correlation with immunomodulatory pathways, immunomodulatory factors and immune markers. In addition, high FAM46C expression correlated with tumour mutational burden in acute myeloid leukaemia and microsatellite instability in endometrial cancer.Conclusion: Our study suggests that FAM46C can be a potential prognostic marker for pan-cancer, is closely associated with immune regulation and may be an immune checkpoint to guide future clinical immunotherapy.
Collapse
Affiliation(s)
- Jiehua Deng
- Centre of Imaging Diagnosis, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Wei Xiao
- Department of Clinical Medicine, Medical College of Shihezi University, Shihezi, China
| | - Zheng Wang
- Centre of Imaging Diagnosis, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- *Correspondence: Zheng Wang,
| |
Collapse
|
|
36
|
Development of the DNA-based biosensors for high performance in detection of molecular biomarkers: More rapid, sensitive, and universal. Biosens Bioelectron 2022; 197:113739. [PMID: 34781175 PMCID: PMC8553638 DOI: 10.1016/j.bios.2021.113739] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 10/25/2021] [Indexed: 02/07/2023]
Abstract
The molecular biomarkers are molecules that are closely related to specific physiological states. Numerous molecular biomarkers have been identified as targets for disease diagnosis and biological research. To date, developing highly efficient probes for the precise detection of biomarkers has become an attractive research field which is very important for biological and biochemical studies. During the past decades, not only the small chemical probe molecules but also the biomacromolecules such as enzymes, antibodies, and nucleic acids have been introduced to construct of biosensor platform to achieve the detection of biomarkers in a highly specific and highly efficient way. Nevertheless, improving the performance of the biosensors, especially in clinical applications, is still in urgent demand in this field. A noteworthy example is the Corona Virus Disease 2019 (COVID-19) that breaks out globally in a short time in 2020. The COVID-19 was caused by the virus called SARS-CoV-2. Early diagnosis is very important to block the infection of the virus. Therefore, during these months scientists have developed dozens of methods to achieve rapid and sensitive detection of the virus. Nowadays some of these new methods have been applied for producing the commercial detection kit and help people against the disease worldwide. DNA-based biosensors are useful tools that have been widely applied in the detection of molecular biomarkers. The good stability, high specificity, and excellent biocompatibility make the DNA-based biosensors versatile in application both in vitro and in vivo. In this paper, we will review the major methods that emerged in recent years on the design of DNA-based biosensors and their applications. Moreover, we will also briefly discuss the possible future direction of DNA-based biosensors design. We believe this is helpful for people interested in not only the biosensor field but also in the field of analytical chemistry, DNA nanotechnology, biology, and disease diagnosis.
Collapse
|
|
37
|
Žvirblytė J, Mažutis L. Microfluidics for Cancer Biomarker Discovery, Research, and Clinical Application. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1379:499-524. [DOI: 10.1007/978-3-031-04039-9_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
|
|
38
|
Smith BJ, Silva-Costa LC, Martins-de-Souza D. Human disease biomarker panels through systems biology. Biophys Rev 2021; 13:1179-1190. [PMID: 35059036 PMCID: PMC8724340 DOI: 10.1007/s12551-021-00849-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 10/01/2021] [Indexed: 12/23/2022] Open
Abstract
As more uses for biomarkers are sought after for an increasing number of disease targets, single-target biomarkers are slowly giving way for biomarker panels. These panels incorporate various sources of biomolecular and clinical data to guarantee a higher robustness and power of separation for a clinical test. Multifactorial diseases such as psychiatric disorders show great potential for clinical use, assisting medical professionals during the analysis of risk and predisposition, disease diagnosis and prognosis, and treatment applicability and efficacy. More specific tests are also being developed to assist in ruling out, distinguishing between, and confirming suspicions of multifactorial diseases, as well as to predict which therapy option may be the best option for a given patient's biochemical profile. As more complex datasets are entering the field, involving multi-omic approaches, systems biology has stepped in to facilitate the discovery and validation steps during biomarker panel generation. Filtering biomolecules and clinical data, pre-validating and cross-validating potential biomarkers, generating final biomarker panels, and testing the robustness and applicability of those panels are all beginning to rely on machine learning and systems biology and research in this area will only benefit from advances in these approaches.
Collapse
Affiliation(s)
- Bradley J. Smith
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
| | - Licia C. Silva-Costa
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
| | - Daniel Martins-de-Souza
- Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil
- Instituto Nacional de Biomarcadores Em Neuropsiquiatria (INBION), Conselho Nacional de Desenvolvimento Científico E Tecnológico, Sao Paulo, Brazil
- Experimental Medicine Research Cluster (EMRC), University of Campinas, Campinas, Brazil
| |
Collapse
|
|
39
|
Wang M, Liu F, Pan Y, Xu R, Li F, Liu A, Yang H, Duan L, Shen L, Wu Q, Liu Y, Liu M, Liu Z, Hu Z, Chen H, Cai H, He Z, Ke Y. Tumor-associated autoantibodies in ESCC screening: Detecting prevalent early-stage malignancy or predicting future cancer risk? EBioMedicine 2021; 73:103674. [PMID: 34753106 PMCID: PMC8586741 DOI: 10.1016/j.ebiom.2021.103674] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 10/19/2021] [Accepted: 10/19/2021] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND To assess potential roles for tumor-associated autoantibodies (TAAs) in esophageal squamous cell carcinoma (ESCC) screening: detecting early-stage malignancy, and predicting future cancer risk. METHOD Thirteen candidate autoantibodies identified in previous literatures were measured using multiplex serological assays in sera from cases and matched controls nested in two population-level screening cohorts in China. To evaluate the role of TAAs in detecting prevalent esophageal malignant lesions, an identification set (150 cases vs. 560 controls) and an external validation set (34 cases vs. 121 controls) were established with pre-screening sera collected ≤ 12 months prior to screening-related diagnosis. To explore the role of TAAs in predicting future ESCC risk, an exploration set (105 cases vs. 416 controls) with pre-diagnostic sera collected > 12 months before clinical diagnosis was established. Two models, the questionnaire-based model and full model additionally incorporating TAA markers, were constructed. Area under the receiver operating characteristic curve (AUC) and net reclassification improvement (NRI) were calculated to compare the performance of the two models. FINDINGS In the identification set, NY-ESO-1 (OR=2·12, 95% CI=1·02-4·40) and STIP1 (OR=1·83, 95% CI=1·10-3·05) were positively associated with higher risk of esophageal malignancy. Elevated MMP-7 was associated with higher risk of malignancy in females (ORfemale=5·07, 95% CI=1·30-19·71). The estimates in validation set were consistent with these results, but were close to null in exploration set. Integration of selected TAAs improved the performance of questionnaire-based models in detecting prevalent esophageal malignancy (female: AUCfull model=0·745, 95% CI=0·675-0·814, AUCquestionnaire-based model=0·658, 95% CI=0·585-0·732, NRI=0·604, P<0·0001; male: AUCfull model=0·662, 95% CI=0·596-0·728, AUCquestionnaire-based model=0·619, 95% CI=0·548-0·690, NRI=0·357, P=0·0028). This improvement was also seen in validation set, but was not similarly effective in distinguishing long-term incident cases from healthy controls. INTERPRETATION Serological autoantibodies against NY-ESO-1, STIP1, and MMP-7 perform well in detecting early-stage esophageal malignancy, but are less effective in predicting future ESCC risks. FUNDING This work was supported by the National Science & Technology Fundamental Resources Investigation Program of China (2019FY101102), the National Natural Science Foundation of China (82073626), the National Key R&D Program of China (2016YFC0901404), the Beijing-Tianjin-Hebei Basic Research Cooperation Project (J200016), the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0204), and the Natural Science Foundation of Beijing Municipality (7182033).
Collapse
Affiliation(s)
- Minmin Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Fangfang Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Yaqi Pan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Ruiping Xu
- Anyang Cancer Hospital, Anyang, Henan Province, P.R. China
| | - Fenglei Li
- Hua County People's Hospital, Anyang, Henan Province, P.R. China
| | - Anxiang Liu
- Endoscopy center, Anyang Cancer Hospital, Anyang, Henan Province, P.R. China
| | - Haijun Yang
- Department of pathology, Anyang Cancer Hospital, Anyang, Henan Province, P.R. China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing, P.R. China
| | - Lin Shen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Qi Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Endoscopy Center, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Ying Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Mengfei Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Zhen Liu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Zhe Hu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Huanyu Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Hong Cai
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China
| | - Zhonghu He
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China.
| | - Yang Ke
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Genetics, Peking University Cancer Hospital & Institute, Beijing, P.R. China.
| |
Collapse
|
|
40
|
The role of miRNA125b in the progression of hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2021; 45:101712. [PMID: 33930594 DOI: 10.1016/j.clinre.2021.101712] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Revised: 04/03/2021] [Accepted: 04/19/2021] [Indexed: 02/04/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common tumours worldwide, and identifying markers related to HCC is an important area of research. As a microRNA (miRNA), miRNA125b (miR-125b) plays an important role in the prediction and prognosis of HCC. In the past 10 years, with increasing research on miR-125b and HCC, the molecular mechanism of its relationship with the development of HCC has been elucidated. MiR-125b inhibits the development of HCC and is highly accurate in predicting HCC and is therefore a valuable predictive marker of HCC. This article summarizes the clinical application of miR-125b in HCC and the potential mechanism of its involvement in the progression of HCC.
Collapse
|
|
41
|
Kim S, Ji S, Koh HR. CRISPR as a Diagnostic Tool. Biomolecules 2021; 11:1162. [PMID: 34439828 PMCID: PMC8391464 DOI: 10.3390/biom11081162] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 08/02/2021] [Accepted: 08/03/2021] [Indexed: 12/13/2022] Open
Abstract
Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system has recently gained growing attention as a diagnostic tool due to its capability of specific gene targeting. It consists of Cas enzymes and a guide RNA (gRNA) that can cleave the target DNA or RNA based on the sequence of the gRNA, making it an attractive genetic engineering technique. In addition to the target-specific binding and cleavage, the trans-cleavage activity was reported for some Cas proteins, including Cas12a and Cas13a, which is to cleave the surrounding single-stranded DNA or RNA upon the target binding of Cas-gRNA complex. All these activities of the CRISPR-Cas system are based on its target-specific binding, making it applied to develop diagnostic methods by detecting the disease-related gene as well as microRNAs and the genetic variations such as single nucleotide polymorphism and DNA methylation. Moreover, it can be applied to detect the non-nucleic acids target such as proteins. In this review, we cover the various CRISPR-based diagnostic methods by focusing on the activity of the CRISPR-Cas system and the form of the target. The CRISPR-based diagnostic methods without target amplification are also introduced briefly.
Collapse
Affiliation(s)
| | | | - Hye Ran Koh
- Department of Chemistry, Chung-Ang University, Seoul 06974, Korea; (S.K.); (S.J.)
| |
Collapse
|
|
42
|
Mao CP, Wang SC, Su YP, Tseng SH, He L, Wu AA, Roden RBS, Xiao J, Hung CF. Protein detection in blood with single-molecule imaging. SCIENCE ADVANCES 2021; 7:7/33/eabg6522. [PMID: 34380620 PMCID: PMC8357237 DOI: 10.1126/sciadv.abg6522] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 06/21/2021] [Indexed: 06/13/2023]
Abstract
The ability to characterize individual biomarker protein molecules in patient blood samples could enable diagnosis of diseases at an earlier stage, when treatment is typically more effective. Single-molecule imaging offers a promising approach to accomplish this goal. However, thus far, single-molecule imaging methods have not been translated into the clinical setting. The detection limit of these methods has been confined to the picomolar (10-12 M) range, several orders of magnitude higher than the circulating concentrations of biomarker proteins present in many diseases. Here, we describe single-molecule augmented capture (SMAC), a single-molecule imaging technique to quantify and characterize individual protein molecules of interest down to the subfemtomolar (<10-15 M) range. We demonstrate SMAC in a variety of applications with human blood samples, including the analysis of disease-associated secreted proteins, membrane proteins, and rare intracellular proteins. SMAC opens the door to the application of single-molecule imaging in noninvasive disease profiling.
Collapse
Affiliation(s)
- Chih-Ping Mao
- Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA
- Harvard Medical School, Boston, MA, USA
| | - Shih-Chin Wang
- Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Yu-Pin Su
- Lieber Institute for Brain Development, Baltimore, MD, USA
| | - Ssu-Hsueh Tseng
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Liangmei He
- Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Annie A Wu
- Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Richard B S Roden
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
- Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
- Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore MD, USA
| | - Jie Xiao
- Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Chien-Fu Hung
- Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
- Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA
- Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore MD, USA
| |
Collapse
|
|
43
|
Xi J, Zeng Z, Li X, Zhang X, Xu J. Expression and Diagnostic Value of tRNA-Derived Fragments Secreted by Extracellular Vesicles in Hypopharyngeal Carcinoma. Onco Targets Ther 2021; 14:4189-4199. [PMID: 34285510 PMCID: PMC8286722 DOI: 10.2147/ott.s320176] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 06/29/2021] [Indexed: 12/28/2022] Open
Abstract
OBJECTIVE To detect the expression level of tRNA-derived fragments secreted by extracellular vesicles in hypopharyngeal cancer and explore the influence of tRNA-derived fragments on the occurrence of hypopharyngeal cancer and lung metastasis. METHODS After high-speed centrifugation, tRNA, which was extracted from the extracellular vesicles of patients with hypopharyngeal cancer and healthy subjects, was sequenced using microarrays. The expression of three differentially expressed tRNAs in hypopharyngeal cancer, healthy subjects, human normal laryngeal epithelial cells and hypopharyngeal cancer line was detected by qRT-PCR. The correlation between the upregulated tRNA, as identified by qRT-PCR, and the clinicopathological features of the non-lung metastatic patients was further analyzed. Finally, the expressions of upregulated tRNA were compared between the non-lung metastatic and lung metastatic patients. The risk factors of hypopharyngeal cancer with lung metastatic were identified by the Cox regression analysis. RESULTS By high-speed centrifugation, extracellular vesicles were extracted successfully. It was found that a variety of tRNAs in the extracellular vesicles from patients with hypopharyngeal cancer by sequencing. qRT-PCR validation indicated that tRF-1:30-Lys-CTT-1-M2 was significantly overexpressed in hypopharyngeal cancer patients and tumor cells, especially in lung metastatic patients. It was indicated that tRF-1:30-Lys-CTT-1-M2 overexpression was closely related to such pathological features as tumor staging, differentiation grade, smoking history and drinking history. According to the Cox regression analysis, stage III-IV, smoking history, drinking history and tRF-1:30-Lys-CTT-1-M2 overexpression were independent risk factors for metastasis of hypopharyngeal cancer. CONCLUSION tRF-1:30-Lys-CTT-1-M2 was overexpressed in patients with hypopharyngeal cancer and was identified as an independent risk factor for lung metastasis. It can be used as a novel biomarker for the diagnosis and lung metastasis monitoring of hypopharyngeal cancer.
Collapse
Affiliation(s)
- Jian Xi
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan Province, 410008, People’s Republic of China
- Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, 410008, Hunan, People’s Republic of China
- Department of Neurosurgery, Xiangya Hospital of Central South University, Changsha, Hunan Province, 410008, People’s Republic of China
| | - Zhiming Zeng
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan Province, 410008, People’s Republic of China
- Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, 410008, Hunan, People’s Republic of China
| | - Xin Li
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan Province, 410008, People’s Republic of China
- Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, 410008, Hunan, People’s Republic of China
| | - Xin Zhang
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan Province, 410008, People’s Republic of China
- Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, 410008, Hunan, People’s Republic of China
| | - Jing Xu
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan Province, 410008, People’s Republic of China
- Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, 410008, Hunan, People’s Republic of China
| |
Collapse
|
|
44
|
Zahid OK, Rivas F, Wang F, Sethi K, Reiss K, Bearden S, Hall AR. Solid-state nanopore analysis of human genomic DNA shows unaltered global 5-hydroxymethylcytosine content associated with early-stage breast cancer. NANOMEDICINE : NANOTECHNOLOGY, BIOLOGY, AND MEDICINE 2021; 35:102407. [PMID: 33905828 PMCID: PMC8238847 DOI: 10.1016/j.nano.2021.102407] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 01/31/2021] [Accepted: 04/05/2021] [Indexed: 01/08/2023]
Abstract
5-Hydroxymethylcytosine (5hmC), the first oxidized form of the well-known epigenetic modification 5-methylcytosine, is an independent regulator of gene expression and therefore a potential marker for disease. Here, we report on methods developed for a selective solid-state nanopore assay that enable direct analysis of global 5hmC content in human tissue. We first describe protocols for preparing genomic DNA derived from both healthy breast tissue and stage 1 breast tumor tissue and then use our approach to probe the net abundance of the modified base in each cohort. Then, we employ empirical data to adjust for the impact of nanopore diameter on the quantification. Correcting for variations in nanopore diameter among the devices used for analysis reveals no detectable difference in global 5hmC content between healthy and tumor tissue. These results suggest that 5hmC changes may not be associated with early-stage breast cancer and instead are a downstream consequence of the disease.
Collapse
Affiliation(s)
- Osama K Zahid
- Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Felipe Rivas
- Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Fanny Wang
- Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Komal Sethi
- Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Katherine Reiss
- Department of Engineering, Wake Forest University, Winston-Salem, NC, USA
| | - Samuel Bearden
- Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Adam R Hall
- Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA; Comprehensive Cancer Center, Wake Forest School of Medicine, Winston-Salem, NC, USA.
| |
Collapse
|
|
45
|
Zhong X, Zhang M, Guo L, Xie Y, Luo R, Chen W, Cheng F, Wang L. A dual-signal self-checking photoelectrochemical immunosensor based on the sole composite of MIL-101(Cr) and CdSe quantum dots for the detection of α-fetoprotein. Biosens Bioelectron 2021; 189:113389. [PMID: 34091283 DOI: 10.1016/j.bios.2021.113389] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/15/2021] [Accepted: 05/26/2021] [Indexed: 12/30/2022]
Abstract
Designing a photoelectrochemical (PEC) immunosensor that can produce dual photocurrent signals which can refer to each other is a great importance but a big challenge. In this manuscript, a novel dual photocurrent signals immunosensor was constructed for the detection of α-fetoprotein (AFP). Unlike the usual method of using two composite materials to provide cathode and anode photocurrent respectively, this work applies only one compound of MIL-101 (Cr) and CdSe quantum dots (QDs). Thereinto, we found that the photocurrent polarity of MIL-101(Cr) would switch by adjusting applied voltage. And then CdSe QDs was introduced by simple ultrasound mixing to boost the dual photocurrent signals. Furthermore, in the composite of M&C, the electron transfer path between MIL-101(Cr) and CdSe QDs may switch between "Z-type" and "Ⅱ-type" by adjusting voltage. Benefiting by the dual signals, the proposed sensor can not only perform sensitively quantitative detection of α-fetoprotein (AFP), but also can intuitively estimate the accuracy and reliability of the test result by determining whether the corresponding relationship of "cathode photocurrent-analyte concentration-anode photocurrent" is established. The linear ranges of the sensing electrodes as cathode and anode are the same, both from 0.1 to 300 ng mL-1. The limit of detection (LOD) is 0.082 ng mL-1 (S/N = 3) when it used as an anode, and the LOD is 0.054 ng mL-1 (S/N = 3) when it served as cathode. Furthermore, this sensor showed acceptable stability, reproducibility, specificity, and feasibility of detecting AFP in human serum, which has broad development prospects in the early clinical diagnosis.
Collapse
Affiliation(s)
- Xiaolin Zhong
- Guangdong Engineering and Technology Research Center for Advanced Nanomaterials, School of Environment and Civil Engineering, Dongguan University of Technology, Dongguan, 523808, PR China; School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510641, PR China
| | - Min Zhang
- Guangdong Engineering and Technology Research Center for Advanced Nanomaterials, School of Environment and Civil Engineering, Dongguan University of Technology, Dongguan, 523808, PR China.
| | - Lu'an Guo
- Guangdong Engineering and Technology Research Center for Advanced Nanomaterials, School of Environment and Civil Engineering, Dongguan University of Technology, Dongguan, 523808, PR China
| | - Yongze Xie
- School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510641, PR China
| | - Renfeng Luo
- Guangdong Engineering and Technology Research Center for Advanced Nanomaterials, School of Environment and Civil Engineering, Dongguan University of Technology, Dongguan, 523808, PR China
| | - Wenxue Chen
- Guangdong Engineering and Technology Research Center for Advanced Nanomaterials, School of Environment and Civil Engineering, Dongguan University of Technology, Dongguan, 523808, PR China
| | - Faliang Cheng
- Guangdong Engineering and Technology Research Center for Advanced Nanomaterials, School of Environment and Civil Engineering, Dongguan University of Technology, Dongguan, 523808, PR China.
| | - Lishi Wang
- School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510641, PR China.
| |
Collapse
|
|
46
|
Yang C, Wu T, Zhang J, Liu J, Zhao K, Sun W, Zhou X, Kong X, Shi J. Prognostic and Immunological Role of mRNA ac4C Regulator NAT10 in Pan-Cancer: New Territory for Cancer Research? Front Oncol 2021; 11:630417. [PMID: 34094911 PMCID: PMC8170476 DOI: 10.3389/fonc.2021.630417] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 04/07/2021] [Indexed: 12/02/2022] Open
Abstract
Background NAT10 (also known as human N-acetyltransferase-like protein) is a critical gene that regulates N4-acetylcytidine formation in RNA, similar to the multiple regulators of N6-methyladenosine. However, the underlying functions and mechanisms of NAT10 in tumor progression and immunology are unclear. Methods In this study, we systematically analyzed the pan-cancer expression and correlations of NAT10, using databases including Oncomine, PrognoScan, GEPIA2, and Kaplan-Meier Plotter. The potential correlations of NAT10 with immune infiltration stages and gene marker sets were analyzed using the Tumor Immune Estimation Resource and GEPIA2. Results Compared with normal tissues, NAT10 showed higher expression in most cancers based on combined data from TCGA and GTEx. In different datasets, high NAT10 expression was significantly correlated with poor prognosis in adrenocortical carcinoma, head and neck squamous cell carcinoma, liver hepatocellular carcinoma, kidney renal papillary cell carcinoma, and pheochromocytoma and paraganglioma. Moreover, there were significant positive correlations between NAT10 expression and immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, dendritic cells, endothelial cells, and fibroblasts in LIHC. NAT10 expression showed strong correlations with diverse immune marker gene sets in LIHC. Conclusion NAT10 expression affects the prognosis of pan-cancer patients and is significantly correlated with tumor immune infiltration. Furthermore, it represents a potential target for cancer therapy.
Collapse
Affiliation(s)
- Chuanxi Yang
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.,Department of Cardiology, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
| | - Tingting Wu
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jing Zhang
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jinhui Liu
- Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Kun Zhao
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei Sun
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xin Zhou
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiangqing Kong
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jing Shi
- Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| |
Collapse
|
|
47
|
Gao F, Lei C, Liu Y, Song H, Kong Y, Wan J, Yu C. Rational Design of Dendritic Mesoporous Silica Nanoparticles' Surface Chemistry for Quantum Dot Enrichment and an Ultrasensitive Lateral Flow Immunoassay. ACS APPLIED MATERIALS & INTERFACES 2021; 13:21507-21515. [PMID: 33939415 DOI: 10.1021/acsami.1c02149] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Lateral flow immunoassays (LFIAs) have drawn much attention in point-of-care diagnostic applications, and the development of high-performance label materials is the key. In this study, the impact of the surface chemistry of dendritic mesoporous silica nanoparticles (DMSNs) on their enrichment performance toward quantum dots (QDs) and signal amplification of the resultant DMSNs-QDs as label materials have been investigated. A series of DMSNs with controllable amino/thiol group densities have been synthesized. It is demonstrated that the amino groups are beneficial for QD fluorescence preservation, owing to the amino-based surface passivation, while the thiol groups are responsible for increasing the loading capacity of QDs due to the thiol-metal coordination. The optimized DMSNs-QDs labels with an amino density of 153 μmol g-1 and a thiol density of 218 μmol g-1 displayed sufficient QD fluorescence preservation (89.4%) and high QD loading capacity (1.55 g g-1). Ultrasensitive detection of serum amyloid A (SAA) with a detection limit of 10 pg mL-1 with the naked eye was achieved, which is 1 order of magnitude higher than that reported in the literature. This study provides insights into the development of advanced label materials and an ultrasensitive LFIA for future bioassay applications.
Collapse
Affiliation(s)
- Fang Gao
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia
| | - Chang Lei
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia
| | - Yang Liu
- School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, P. R. China
| | - Hao Song
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia
| | - Yueqi Kong
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia
| | - Jingjing Wan
- School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, P. R. China
| | - Chengzhong Yu
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland 4072, Australia
- School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, P. R. China
| |
Collapse
|
|
48
|
Shafiei M, Alemrajabi M, Najafi A, Keihan AH, Sohrabi MR. Candidate Molecular Biomarkers for the Non- Invasive Detection of Colorectal Cancer using Gene Expression Profiling. IRANIAN JOURNAL OF PATHOLOGY 2021; 16:205-214. [PMID: 33936232 PMCID: PMC8085285 DOI: 10.30699/ijp.2021.132385.2475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 02/17/2021] [Indexed: 11/07/2022]
Abstract
Background & Objective: olorectal Cancer (CRC) is the third most common cancer after prostate (breast in women) and lung cancer; it is also the third cause of cancer deaths reported in both men and women in 2020. Currently, the most commonly used diagnostic tools for CRC are colonoscopy, serological methods, and other imaging techniques. Despite the benefits and abilities of these methods, each of them has disadvantages that reduce its functionality and acceptance. The aim of this study was identifying specific and non-invasive genetic biomarkers to diagnose colorectal cancer. Methods: In this study, changes in the expression of HLTF and SEPT9 genes were evaluated by Real Time PCR in blood and tissue samples of CRC patients. A total of 100 samples (50 Blood and 50 Tissue samples) were evaluated with a definite diagnosis of CRC in Firoozgar Hspital, Tehran, Iran, in 2018. The QPCR method was used to compare the expression of candidate genes between the patients group and control group in both samples. Sensitivity and specificity of the test were examined using ROC curve analysis. Results: The results showed a significant down-regulation in the expression of both selected genes in tissue and peripheral blood in the various stages of the CRC. The sensitivity and specifity of both genes was about 80%. Conclusion: The findings showed that the two candidate genes can be suggested as specific biomarkers for diagnosis of CRC using the peripheral blood as a non-invasive method. For a definite conclusion, more research is needed.
Collapse
Affiliation(s)
- Mohammad Shafiei
- Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mahdi Alemrajabi
- Gastrointestinal and Liver Disease Research Center (GILDRC), Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Najafi
- Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Amir Homayoun Keihan
- Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Masoud Reza Sohrabi
- Gastrointestinal and Liver Disease Research Center (GILDRC), Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
49
|
Gao F, Liu Y, Lei C, Liu C, Song H, Gu Z, Jiang P, Jing S, Wan J, Yu C. The Role of Dendritic Mesoporous Silica Nanoparticles' Size for Quantum Dots Enrichment and Lateral Flow Immunoassay Performance. SMALL METHODS 2021; 5:e2000924. [PMID: 34927850 DOI: 10.1002/smtd.202000924] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 01/18/2021] [Indexed: 06/14/2023]
Abstract
Using dendritic mesoporous silica nanoparticles (DMSNs) for quantum dots (QDs) enrichment and signal amplification is an emerging strategy for improving the detection sensitivity of lateral flow immunoassay (LFIA). In this study, a new and convenient approach is developed to prepare water-dispersible DMSNs-QDs. A series of DMSNs with various diameters (138, 251, 368, and 471 nm) are studied for loading QDs and LFIA applications. The resultant water-dispersible DMSNs-QDs exhibit a high fluorescence retention of 81.8%. The increase in particle size from 138 to 471 nm results in an increase in loading capacity of QDs and a decrease in binding quantity of the DMSNs-QDs in the test line of LFIA. This trade-off leads to an optimal DMSNs-QDs size of 368 nm with a limit of detection reaching 10 pg mL-1 (equivalent to 9.0 × 10-14 m) for the detection of C-reactive protein, which is nearly an order of magnitude more sensitive than the literature. To the best of the authors' knowledge, this study is the first to demonstrate the distinctive role of DMSN's size for QDs enrichment and LFIA. The strategy developed from this work is useful for the rational design of high-quality QDs-based nanoparticles for ultrasensitive detection.
Collapse
Affiliation(s)
- Fang Gao
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, 4072, Australia
| | - Yang Liu
- School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, P. R. China
| | - Chang Lei
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, 4072, Australia
| | - Chao Liu
- School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, P. R. China
| | - Hao Song
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, 4072, Australia
| | - Zhengying Gu
- School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, P. R. China
| | - Pei Jiang
- Shanghai Fosun Long March Medical Science Company Limited, Shanghai, 200444, P. R. China
| | - Sheng Jing
- Shanghai Fosun Long March Medical Science Company Limited, Shanghai, 200444, P. R. China
| | - Jingjing Wan
- School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, P. R. China
| | - Chengzhong Yu
- Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, 4072, Australia
- School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, P. R. China
| |
Collapse
|
|
50
|
Lommen K, Vaes N, Aarts MJ, van Roermund JG, Schouten LJ, Oosterwijk E, Melotte V, Tjan-Heijnen VC, van Engeland M, Smits KM. Diagnostic DNA Methylation Biomarkers for Renal Cell Carcinoma: A Systematic Review. Eur Urol Oncol 2021; 4:215-226. [PMID: 31402218 DOI: 10.1016/j.euo.2019.07.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 06/23/2019] [Accepted: 07/16/2019] [Indexed: 01/22/2023]
Abstract
CONTEXT The 5-yr survival of early-stage renal cell carcinoma (RCC) is approximately 93%, but once metastasised, the 5-yr survival plummets to 12%, indicating that early RCC detection is crucial to improvement in survival. DNA methylation biomarkers have been suggested to be of potential diagnostic value; however, their current state of clinical translation is unclear and a comprehensive overview is lacking. OBJECTIVE To systematically review and summarise all literature regarding diagnostic DNA methylation biomarkers for RCC. EVIDENCE ACQUISITION We performed a systematic literature review of PubMed, EMBASE, Medline, and Google Scholar up to January 2019, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. Included studies were scored according to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forest plots were generated to summarise diagnostic performance of all biomarkers. Level of evidence (LoE) and potential risk of bias were determined for all included studies. EVIDENCE SYNTHESIS After selection, 19 articles reporting on 44 diagnostic DNA methylation biomarkers and 11 multimarker panels were included; however, only 15 biomarkers were independently validated. STARD scores varied from 4 to 13 out of 23 points, with a median of 10 points. Large variation in subgroups, methods, and primer locations was observed. None of the reported biomarkers exceeded LoE III, and the majority of studies reported inadequately. CONCLUSIONS None of the reported biomarkers exceeded LoE III, indicating their limited clinical utility. Moreover, study reproducibility and further development of these RCC biomarkers are greatly hampered by inadequate reporting. PATIENT SUMMARY In this report, we reviewed whether specific biomarkers could be used to diagnose the most common form of kidney cancer. We conclude that due to limited evidence and reporting inconsistencies, none of these biomarkers can be used in clinical practice, and further development towards clinical use is hindered.
Collapse
Affiliation(s)
- Kim Lommen
- Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Nathalie Vaes
- Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Maureen J Aarts
- Department of Medical Oncology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Joep G van Roermund
- Department of Urology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Leo J Schouten
- Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
| | | | - Veerle Melotte
- Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Vivianne C Tjan-Heijnen
- Department of Medical Oncology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Manon van Engeland
- Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Kim M Smits
- Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands; Department of Medical Oncology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
| |
Collapse
|