Article
Chemistry, Medicinal
Michael A. Plunk, Jeremy M. Quintana, Carly M. Darden, Michael C. Lawrence, Bashoo Naziruddin, Robert R. Kane
Summary: Mycophenolic acid and its prodrug derivatives, used in solid organ transplantation to prevent rejection, were designed to provide localized immunosuppression through specific mechanisms. In vitro studies showed that these prodrugs were inactive against IMPDH and had reduced toxicity compared to the active drug, suggesting their potential for targeted immunosuppression.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biotechnology & Applied Microbiology
Haotian Luo, Danying Chen, Ruoyu Li, Runze Li, Yungshan Teng, Yang Cao, Xuenong Zou, Weicai Wang, Chen Zhou
Summary: Biofilm-related diseases are difficult to treat due to their tolerance to antimicrobial chemotherapies. Periodontitis, a chronic biofilm disease induced by dental plaque, provides a good model to study the effects of host factors on the biofilm microenvironment. This study confirmed the reduction of microRNA-126 (miR-126) with the recruitment of macrophages in periodontitis and explored a strategy for targeted delivery of miR-126 to macrophages. Exosomes overexpressing CXCR4 and loaded with miR-126 successfully regulated macrophages and reduced bone resorption and osteoclastogenesis in periodontitis. These findings provide new insights for the treatment of periodontitis and other biofilm-related diseases.
JOURNAL OF NANOBIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Qinqin Cheng, Zhefu Dai, Goar Smbatyan, Alan L. Epstein, Heinz-Josef Lenz, Yong Zhang
Summary: Researchers designed genetically engineered exosomes with displayed antibodies and immunomodulatory proteins for immunotherapy of breast cancer. These exosomes can redirect and activate T cells to kill cancer cells and induce potent anti-tumor immune responses.
Article
Engineering, Biomedical
Nishta Krishnan, Fei-Xing Peng, Animesh Mohapatra, Ronnie H. Fang, Liangfang Zhang
Summary: In recent years, researchers have increasingly explored nanoparticles derived from cellular membranes for disease prevention and treatment. These biomimetic nanoparticles, with their flexible design and effective interaction with the surrounding environment, can outperform traditional synthetic nanoparticles. Genetic manipulation has proven to be a robust and flexible method to generate nanoformulations with augmented functionalities. This review provides an overview of genetic engineering approaches to express novel surface proteins and discusses the various biomedical applications of genetically modified cellular nanoparticles.
Article
Engineering, Environmental
Xinzhu Shan, Zhiqiang Zhao, Chen Wang, Jin Sun, Zhonggui He, Cong Luo, Shenwu Zhang
Summary: This review discusses the application of prodrug-engineered nanomedicines in synergistic chemo-phototherapy. They offer advantages of synergistic treatment effect and dosage reduction, but also face challenges in design rationale.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Pharmacology & Pharmacy
Abigail Sharrock, Sarah P. McManaway, Michelle H. Rich, Jeff S. Mumm, Ian F. Hermans, Moana Tercel, Frederik B. Pruijn, David F. Ackerley
Summary: Bacterial nitroreductase enzymes have various applications in converting nitroaromatic prodrugs to cytotoxic forms. By engineering E. coli NfsA for enhanced activity with therapeutic prodrugs, a superior broad-range nitroreductase was developed with potential advantages for targeted cellular ablation and suicide gene therapy.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Aristea Anna Leventi, Henry J. Braddick, Kharmen Billimoria, Gregory Q. Wallace, Heidi Goenaga-Infante, Nicholas C. O. Tomkinson, Karen Faulds, Duncan Graham
Summary: This article reports the synthesis of nanocarriers for delivering the antitumor drug cisplatin. Multimodal imaging techniques, including surface enhanced Raman scattering and laser ablation inductively coupled plasma time of flight mass spectrometry, were used to visualize the intracellular uptake of both the nanocarrier and drug.
CHEMICAL COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Abigail V. Sharrock, Jeff S. Mumm, Gintautas Bagdziunas, Narimantas Cenas, Vickery L. Arcus, David F. Ackerley
Summary: Researchers recently engineered an improved bacterial nitroreductase (NTR 2.0) that converts the prodrug metronidazole to a cytotoxin more efficiently. This allows for faster cell ablation, more precise study of cell function, elimination of previously resistant cell types, and the ability to model chronic diseases. X-ray crystal structure analysis and molecular modeling were used to investigate the enhanced enzymatic mechanism and predicted binding modes of key substrates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Yue Dai, Xiaopei Wu, Yihua Yin, Honglian Dai
Summary: Novel prodrugs designed for transdermal delivery of 2-sulfonyl-1-methylimidazole (MMI) were synthesized and characterized. These prodrugs showed significantly enhanced permeation through rat skin compared to MMI, which can be attributed to their improved lipophilicity and rapid bioconversion. The prodrugs were hydrolyzed by esterase when passing through the skin, releasing MMI in response to the intracellular environment. The prodrug with lauryl alcohol ester exhibited a strong inhibition effect on lactoperoxidase (LPO) in the presence of millimolar levels of GSH, similar to free MMI.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Chemistry, Physical
Yuequan Wang, Qian Qiu, Rui Liao, Xinhui Wang, Ziran Zhou, Xuanbo Zhang, Haotian Zhang, Zhonggui He, Shenwu Zhang, Cong Luo, Jin Sun
Summary: Self-engineered small-molecule prodrug-nanoassemblies are promising nanomedicines for cancer treatment. The number, position, and configuration of double bonds in unsaturated fatty acids have significant effects on the nanoassembly and drug delivery of thioether-linked paclitaxel prodrug-nanoassemblies.
Review
Biochemistry & Molecular Biology
Jiexi Liu, Fei Wang, Yang Qin, Xiaolan Feng
Summary: Genetically encoded PSs are important for improving the efficiency of PDT, as they can be modified using genetic engineering techniques, targeted to specific cellular compartments, and even within a single cell. The dimeric red fluorescent protein, KillerRed, can be activated by visible light to execute the Type I reaction of PDT, which does not require much oxygen, making it an attractive option for researchers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Jianzhong Zhang, Xue Liu, Yutian Xia, Shuyu Xu, Xuan Liu, Haiqing Xiao, Xiaoyong Wang, Chao Liu, Gang Liu
Summary: A novel genetically engineered vesicular antibody-melittin (VAM) drug delivery platform was developed for targeted cancer combination therapy. The VAM could release nanomelittin at tumor sites in a controlled manner, reducing off-target toxicity and allowing co-delivery of small-molecule drugs or nanoparticles. This strategy achieved enhanced therapeutic effects through the synergistic action of nanomelittin and anticancer agents.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Biotechnology & Applied Microbiology
Carlos Roman Collazo, Karen Chacha Guerrero, Tatiana Loja Mejia, Diego Andrade Campoverde, Yenima Hernandez Rodriguez
Summary: Partial approval of GMO use is research-oriented, with a rejection toward food. The linear regression model explained 65% of the variance of attitude toward GMOs from the beliefs, practices, knowledge, and bioethical approach variables. The sociodemographic variables were completely excluded from the model due to the absence of statistical significance.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biochemical Research Methods
Ssu-Tzu Tsai, Wen-Jui Cheng, Qian-Xian Zhang, Yi-Chun Yeh
Summary: Transcription factor-based whole-cell biosensors are a promising alternative to traditional analytical methods due to their simplicity, cost-effectiveness, and environmental friendliness. Through genetic engineering, a biosensor strain was developed that showed significant improvement in gold-specificity performance, with a detection sensitivity 42-fold higher than wild-type strains. The proposed sensor demonstrated a linear range of 125-1000 nM and a detection limit of 46.5 nM, effectively validated in wastewater samples.
ACS SYNTHETIC BIOLOGY
(2021)
Review
Engineering, Biomedical
Yu Chen, Xiaoqing Liu, Yanxia Guo, Jianchuan Wang, Dingxiao Zhang, Yang Mei, Junfeng Shi, Wenzhi Tan, Jin Hai Zheng
Summary: Drug delivery systems based on genetically engineered oncolytic bacteria have unique properties that enable them to target tumor tissues and suppress tumor growth effectively, showing potential value for clinical applications. By integrating oncolytic bacteria into cancer therapies, novel strategies are being developed to improve and standardize current treatment regimens in the near future.
ACTA BIOMATERIALIA
(2021)
Article
Multidisciplinary Sciences
Alison Jones, Mark Pitts, Juma'a R. Al Dulayymi, James Gibbons, Andrew Ramsay, Delia Goletti, Christopher D. Gwenin, Mark S. Baird
Article
Pharmacology & Pharmacy
Patrick Ball, Emma Thompson, Simon Anderson, Vanessa Gwenin, Chris Gwenin
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2019)
Review
Nanoscience & Nanotechnology
Simon D. Anderson, Vanessa V. Gwenin, Christopher D. Gwenin
NANOSCALE RESEARCH LETTERS
(2019)
Review
Food Science & Technology
Robert J. Hobbs, Carol A. Thomas, Jennifer Halliwell, Christopher D. Gwenin
Article
Chemistry, Analytical
Alice Jane Heeroma, Christopher Gwenin
Article
Microbiology
Patrick Ball, Jennifer Halliwell, Simon Anderson, Vanessa Gwenin, Christopher Gwenin
Article
Chemistry, Analytical
Joshua Davies, Carol Thomas, Mohammad Rizwan, Christopher Gwenin
Summary: The pH drop in the hindgut of horses, caused by lactic acid-producing bacteria due to excessive carbohydrate intake, can lead to hindgut acidosis and laminitis. By using an electrochemical biosensor, early detection and adjustment of the horse's diet can help prevent these conditions by targeting the responsible bacterial DNA.
Article
Pharmacology & Pharmacy
Patrick Ball, Robert Hobbs, Simon Anderson, Emma Thompson, Vanessa Gwenin, Christopher Von Ruhland, Christopher Gwenin
Summary: The nitroreductase NfnB has been studied for use in directed enzyme prodrug therapy with CB1954, but faces limitations such as a Km value exceeding the maximum dosage of CB1954. New enzymes, like the YfkO nitroreductase, are being investigated for their lower Km values and more favorable enzymatic product ratios.
Review
Biology
Carol Thomas, Christopher D. Gwenin
Summary: Antimicrobial resistance remains a significant global health threat, with an estimated 700,000 deaths annually and a projected cost exceeding $100 trillion. The need for new, effective treatments has increased, leading to a focus on nitroimidazoles due to their broad spectrum of activity against various bacteria. Understanding the role of nitroreductases in activating antimicrobials and their association with resistance mechanisms is crucial for developing strategies against multidrug-resistant organisms. Research collaborations between the private and public sectors are essential for translating academic findings into clinical applications.
Article
Chemistry, Physical
Bazilah Awang Abd Manaf, Shyang Pei Hong, Mohammad Rizwan, Fareeha Arshad, Christopher Gwenin, Minhaz Uddin Ahmed
Summary: Carcinoembryonic antigen (CEA) is a prominent cancer biomarker that allows for early diagnosis of various cancers. Nanomaterial-based immunosensors have gained attention for their high specificity and low detection limit in detecting CEA biomarkers. Various nanomaterials like platinum, gold, silver, and carbon have shown promising results in the detection and diagnostics of CEA. This review explores the significance and recent developments of nanomaterial-based biosensors for detecting CEA biomarkers with high sensitivity, selectivity, and specificity.
SURFACES AND INTERFACES
(2023)
Article
Biochemistry & Molecular Biology
Patrick Ball, Emma Thompson, Simon Anderson, Vanessa Gwenin, Amir Ashoorzadeh, Jeff Smaill, Chris Gwenin
Summary: Directed enzyme prodrug therapy, a promising anti-cancer strategy, is limited by inefficient prodrug activation and dose-limiting toxicity. To overcome these limitations, dinitrobenzamide mustard prodrugs PR-104A and SN27686 have been developed. This study assesses their potential use in a magnetic-nanoparticle directed enzyme prodrug therapy strategy by determining their kinetic parameters, evaluating the enzymatic reduction products using HPLC, and testing their ability to induce cell death in ovarian cancer cell line SK-OV-3. The results demonstrate that the dinitrobenzamide mustard prodrugs can be reduced by genetically modified nitroreductases and induce significant cell death, highlighting their potential for use in this therapy.
BIOSCIENCE REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Alison Jones, Carys A. Davies, Samuel Fitch, Juma'a R. Al Dulayymi, Christopher D. Gwenin, James Gibbons, A. Prysor Williams, Mark S. Baird
Summary: The study conducted ELISA tests on serum samples from different populations to detect antibody responses to mycobacterial esters, finding that individuals exposed to mycobacteria, such as farmers, showed significantly higher antibody responses, especially older farmers. This suggests that mycobacterial exposure may lead to differences in antibody responses among different population groups.
RSC MEDICINAL CHEMISTRY
(2021)
Review
Physiology
Carol Jones, Christopher Gwenin
Summary: This review examines the role of the stress hormone cortisol in regulating bodily functions and its impact on health, especially in chronic conditions. It emphasizes the importance of timely detection, screening, and treatment for noncommunicable diseases, and highlights the pro-inflammatory consequences of cortisol dysregulation and its deleterious effects on the body. The relevance of these findings is particularly evident in light of recent research on COVID-19 and its pro-inflammatory cytokines linked to severe inflammation.
PHYSIOLOGICAL REPORTS
(2021)
Article
Engineering, Biomedical
Simon D. Anderson, Robert J. Hobbs, Vanessa V. Gwenin, Patrick Ball, Lindsey A. Bennie, Jonathan A. Coulter, Chris D. Gwenin
JOURNAL OF FUNCTIONAL BIOMATERIALS
(2019)
Article
Chemistry, Analytical
Victor O. Ebuele, Daniel G. Congrave, Chris D. Gwenin, Vera Fitzsimmons-Thoss
ANALYTICAL LETTERS
(2018)