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Keywords = Bioconjugates

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24 pages, 3143 KB  
Article
Modulating Peroxidase-like Activity of Fe3O4@Pt@poly-LDOPA and Its Application as Multifunctional Magnetic Probes Towards SARS-CoV-2 Detection
by Lorico Delos Santos Lapitan, Jan Olgierd Górniaszek, Maciej Trzaskowski and Mariusz Pietrzak
Appl. Sci. 2026, 16(4), 1858; https://doi.org/10.3390/app16041858 - 12 Feb 2026
Viewed by 378
Abstract
We report a Fe3O4@Pt@poly-LDOPA nanozyme that displays enhanced peroxidase (POD)-like activity. Polymerisation of levodopa onto the surface of Fe3O4@Pt yields a carboxyl-rich poly-LDOPA shell that is available for bioconjugation with antibodies and other types of [...] Read more.
We report a Fe3O4@Pt@poly-LDOPA nanozyme that displays enhanced peroxidase (POD)-like activity. Polymerisation of levodopa onto the surface of Fe3O4@Pt yields a carboxyl-rich poly-LDOPA shell that is available for bioconjugation with antibodies and other types of receptors. Physicochemical characterisation confirmed the integrity of the Fe3O4 core, successful Pt modification, and formation of the polymer coating under acidic and basic conditions. Steady-state kinetic analysis using the Michaelis–Menten model revealed robust catalytic performance toward both substrates: for H2O2, Vmax = 4.0 × 10−8 M·s−1 and Km = 25.13 mM; for TMB, Vmax = 6.07 × 10−8 M·s−1 and Km = 0.229 mM, indicative of high turnover and strong apparent affinity for the chromogenic substrate. A nanozyme-linked immunosorbent assay for the SARS-CoV-2 nucleocapsid was developed. The anti-nucleocapsid antibodies were immobilised onto Fe3O4@Pt@poly-LDOPA via EDC/NHS. In buffer, the calibration range (1.0–100 ng·mL−1) afforded an LOD of 6.95 ng·mL−1. In 10% human serum, reduced background and improved nanozyme dispersion yielded a linear low-concentration response (0.1–10 ng·mL−1), with an LOD of 0.0036 ng·mL−1. These results establish Fe3O4@Pt@poly-LDOPA as a promising inorganic–organic nanozyme platform that combines catalytic effectiveness, magnetic manipulability, and facile bioconjugation for immunosensing of various disease-related biomarkers. Full article
(This article belongs to the Special Issue Application of Magnetic Nanoparticles)
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30 pages, 5119 KB  
Article
Parasporin-2-Derived Peptide Fragments: Characterization and Synergistic Anticancer Activity with Sacha Inchi and Curcumin
by Natalia Ardila, Fanny Guzmán, Miguel O. Suárez-Barrera and Jenniffer Cruz
Cancers 2026, 18(3), 451; https://doi.org/10.3390/cancers18030451 - 30 Jan 2026
Viewed by 207
Abstract
Background/Objectives: Parasporin PS2Aa1, recently designated as Mpp46Aa1, is recognized for its selective anticancer activity against various human cell lines. In this study, specific regions of the native protein were fragmented, and targeted amino acid substitutions were introduced to improve cytotoxic selectivity and potency. [...] Read more.
Background/Objectives: Parasporin PS2Aa1, recently designated as Mpp46Aa1, is recognized for its selective anticancer activity against various human cell lines. In this study, specific regions of the native protein were fragmented, and targeted amino acid substitutions were introduced to improve cytotoxic selectivity and potency. Methods: The modified fragments were evaluated individually and in combination with curcumin, a polyphenol with well-documented anticancer properties, and Sacha inchi-derived matrices, known for their antioxidant and antiproliferative activities. Results: Experimental results demonstrated that the substituted variant designated T104L-G108W exhibited superior anticancer activity compared to the native peptide P102-K11. Synergism assays revealed that curcumin-bioconjugated peptides were more effective against the tested cell lines, whereas combinations with Sacha inchi reduced cytotoxicity, suggesting possible interference in the mechanisms of action. Functional assays, including caspase 3/7 and 9 activation, Annexin V-Cy3 staining, and cell viability analysis with 6-CFDA, confirmed increased sensitivity in SiHa and HeLa cell lines, particularly for peptide T104L-G108W. Conclusions: Collectively, these findings support the effectiveness of a substitution-based strategy in improving parasporin fragments and underscore the therapeutic potential of peptide T104L-G108W as a novel anticancer candidate. Furthermore, this study provides preliminary evidence that natural biomolecules can be optimized through targeted modifications and rational combinations, establishing a framework for the development of sustainable and selective therapeutic approaches in cancer treatment. Full article
(This article belongs to the Collection The Development of Anti-cancer Agents)
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41 pages, 3913 KB  
Review
Advancing Bioconjugated Quantum Dots with Click Chemistry and Artificial Intelligence to Image and Treat Glioblastoma
by Pranav Kalaga and Swapan K. Ray
Cells 2026, 15(2), 185; https://doi.org/10.3390/cells15020185 - 19 Jan 2026
Viewed by 793
Abstract
Glioblastoma (GB) is one of the most aggressive and invasive cancers. Current treatment protocols for GB include surgical resection, radiotherapy, and chemotherapy with temozolomide. However, despite these treatments, physicians still struggle to effectively image, diagnose, and treat GB. As such, patients frequently experience [...] Read more.
Glioblastoma (GB) is one of the most aggressive and invasive cancers. Current treatment protocols for GB include surgical resection, radiotherapy, and chemotherapy with temozolomide. However, despite these treatments, physicians still struggle to effectively image, diagnose, and treat GB. As such, patients frequently experience recurrence of GB, demanding innovative strategies for early detection and effective therapy. Bioconjugated quantum dots (QDs) have emerged as powerful nanoplatforms for precision imaging and targeted drug delivery due to their unique optical properties, tunable size, and surface versatility. Due to their extremely small size, QDs can cross the blood–brain barrier and be used for precision imaging of GB. This review explores the integration of QDs with click chemistry for robust bioconjugation, focusing on artificial intelligence (AI) to advance GB therapy, mechanistic insights into cellular uptake and signaling, and strategies for mitigating toxicity. Click chemistry enables site-specific and stable conjugation of targeting ligands, peptides, and therapeutic agents to QDs, enhancing selectivity and functionalization. Algorithms driven by AI may facilitate predictive modeling, image reconstruction, and personalized treatment planning, optimizing QD design and therapeutic outcomes. We discuss molecular mechanisms underlying interactions of QDs with GB, including receptor-mediated endocytosis and intracellular trafficking, which influence biodistribution and therapeutic efficacy. Use of QDs in photodynamic therapy, which uses reactive oxygen species to induce apoptotic cell death in GB cells, is an innovative therapy that is covered in this review. Finally, this review addresses concerns associated with the toxicity of metal-based QDs and highlights how QDs can be coupled with AI to develop new methods for precision imaging for detecting and treating GB for induction of apoptosis. By converging nanotechnology and computational intelligence, bioconjugated QDs represent a transformative platform for paving a safer path to smarter and more effective clinical interventions of GB. Full article
(This article belongs to the Special Issue Cell Death Mechanisms and Therapeutic Opportunities in Glioblastoma)
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52 pages, 16801 KB  
Review
Delving into the Inception of BODIPY Dyes: Paradigms of In Vivo Bioimaging, Chemosensing, and Photodynamic/Photothermal Therapy
by Olivia Basant, Edgardo Lobo, Gyliann Peña and Maged Henary
Pharmaceuticals 2026, 19(1), 169; https://doi.org/10.3390/ph19010169 - 18 Jan 2026
Viewed by 507
Abstract
Boron-dipyrromethene (BODIPY) dyes belong to a class of organoboron compounds that have become ubiquitous for researchers in areas of fluorescence imaging, photodynamic therapy, and optoelectronics. The intrinsic qualities of BODIPY dyes and their meso-modified structural analogs, Aza-BODIPY dyes, have propelled their recent increase [...] Read more.
Boron-dipyrromethene (BODIPY) dyes belong to a class of organoboron compounds that have become ubiquitous for researchers in areas of fluorescence imaging, photodynamic therapy, and optoelectronics. The intrinsic qualities of BODIPY dyes and their meso-modified structural analogs, Aza-BODIPY dyes, have propelled their recent increase in use in biomedical applications. The two scaffolds have high quantum yields, narrow absorption, and emission bandwidths with large Stokes’ shifts, and high photostability and thermal stability. Because their properties are independent of solvent polarity and dye functionality, they can be tuned to promote novel analytical methods, resulting in the adaptation of the physicochemical and spectral properties of the dyes. In this review of BODIPY and Aza-BODIPY scaffolds, we will summarize their spectral properties, synthetic methods of preparation, and applications reported between 2014 and 2025. This review aims to summarize the advances in chemosensing, especially pH sensor development, and the advances in NIR-II window bioimaging probes. We hope that this succinct overview of Aza-BODIPY scaffolds will highlight their untapped potential, elucidating insights that may catalyze novel ideas in the physical organic realm of BODIPY. Full article
(This article belongs to the Special Issue Photodynamic Therapy: 3rd Edition)
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17 pages, 2302 KB  
Article
Engineered GO-Based Hydrogels for Controlled Hyaluronic Acid Release in Knee Osteoarthritis Treatment
by Roya Binaymotlagh, Damiano Petrilli, Laura Chronopoulou, Giorgio Mandato, Francesca Sciandra, Andrea Brancaccio, Marisa Colone, Annarita Stringaro, Leonardo Giaccari, Francesco Amato, Andrea Giacomo Marrani, Silvia Franco, Roberta Angelini and Cleofe Palocci
Polymers 2026, 18(2), 152; https://doi.org/10.3390/polym18020152 - 6 Jan 2026
Cited by 1 | Viewed by 587
Abstract
Osteoarthritis (OA) is a prevalent chronic pain syndrome and a leading cause of disability worldwide, characterized by progressive deterioration of articular cartilage. This degradation leads to pain, swelling, inflammation, and eventual stiffness as the cartilage wears down, causing bone-on-bone friction. Current medical treatments [...] Read more.
Osteoarthritis (OA) is a prevalent chronic pain syndrome and a leading cause of disability worldwide, characterized by progressive deterioration of articular cartilage. This degradation leads to pain, swelling, inflammation, and eventual stiffness as the cartilage wears down, causing bone-on-bone friction. Current medical treatments primarily aim at pain relief; however, many interventions, especially invasive or surgical ones, carry risks of adverse outcomes. Consequently, intra-articular (IA) therapy, particularly hyaluronic acid (HA) injections, is widely adopted as a conservative treatment option. HA plays a crucial role in maintaining joint homeostasis by supporting proteoglycan synthesis and scaffolding, restoring optimal HA concentrations in synovial fluid, and providing chondroprotective and anti-inflammatory effects. In recent years, hydrogels composed of natural and synthetic materials have emerged as promising candidates for OA treatment. Our research focuses on the biosynthesis and characterization of novel hydrogel composites combining short peptide hydrogelators with aminated graphene oxide (a-GO) nanosheets functionalized with HA (a-GO-HA@Hgel). These a-GO-HA@Hgel nanocomposites are designed to facilitate the controlled release of HA into the extracellular matrix, aiming to promote cartilage regeneration and mitigate inflammation. The strategy is to exploit the oxygen-containing functional groups of GO nanosheets to enable covalent coupling or physical adsorption of HA molecules through various chemical approaches. The resulting a-GO-HA are incorporated within hydrogel matrices to achieve sustained and controlled HA release. We study the influence of a-GO-HA on the native hydrogel structure and its viscoelastic properties, which are critical for mimicking the mechanical environment of native cartilage tissue. Through this multidisciplinary approach combining advanced materials science and cellular biology, this work aims to develop innovative nanocomposite hydrogels capable of delivering HA in a controlled manner, enhancing cartilage repair and providing a potential therapeutic strategy for OA management. Full article
(This article belongs to the Special Issue Advances in Polymer Hydrogels for Biomedical Applications)
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19 pages, 6840 KB  
Article
Magnetically Recoverable ICT-Functionalized Fe3O4 Nanoparticles for Efficient Horseradish Peroxidase Immobilization
by Katarina Isaković, Marko Jonović, Dušan Sredojević, Marko Bošković, Jovana Periša, Zorica Knežević-Jugović and Vesna Lazić
Molecules 2026, 31(1), 178; https://doi.org/10.3390/molecules31010178 - 2 Jan 2026
Viewed by 606
Abstract
The formation of interfacial charge transfer (ICT) complexes between phenolic ligands and metal oxide surfaces enables surface functionalization strategies with potential applications in catalysis and bioconjugation. In this study, magnetite (Fe3O4) nanoparticles were modified with two phenolic ligands, 5-aminosalicylic [...] Read more.
The formation of interfacial charge transfer (ICT) complexes between phenolic ligands and metal oxide surfaces enables surface functionalization strategies with potential applications in catalysis and bioconjugation. In this study, magnetite (Fe3O4) nanoparticles were modified with two phenolic ligands, 5-aminosalicylic acid (5ASA) and caffeic acid (CA), to generate ICT complexes capable of covalent or non-covalent enzyme immobilization, respectively. The modified nanomaterials were structurally characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FTIR). Horseradish peroxidase (HRP) was immobilized on these functionalized supports using varying nanoparticle amounts (10–30 mg) and initial enzyme concentrations (25–250 µg mL−1). Catalytic activity was evaluated using pyrogallol oxidation assays. The Fe3O4/5ASA–HRP system exhibited a maximum activity of 2.5 U per 20 mg of support (approximately 125 U g−1), whereas Fe3O4/CA showed minimal activity under the same conditions. Enzyme loading studies confirmed that 5ASA-enabled covalent attachment resulted in significantly higher immobilization efficiency (up to 1068 mg g−1) compared to the CA system. Reusability tests demonstrated that the Fe3O4/5ASA system retained high absolute catalytic activity during the initial reaction cycles and consistently outperformed the non-covalently immobilized Fe3O4/CA system upon repeated reuse. The magnetic properties of Fe3O4 allowed rapid recovery of the biocatalysts using an external magnetic field. These results highlight the effectiveness of ICT-based functionalization for enzyme immobilization, positioning Fe3O4/5ASA as a promising platform for robust and reusable biocatalysts in environmental and industrial applications. Full article
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44 pages, 6811 KB  
Review
Biomolecule–Photosensitizer Conjugates: A Strategy to Enhance Selectivity and Therapeutic Efficacy in Photodynamic Therapy
by Dominik M. Płaskonka, Dominik Barczyk, Paweł Repetowski, Marta Warszyńska and Janusz M. Dąbrowski
Pharmaceuticals 2026, 19(1), 65; https://doi.org/10.3390/ph19010065 - 29 Dec 2025
Viewed by 826
Abstract
Biomolecule–photosensitizer conjugates have rapidly evolved into one of the most powerful strategies for improving the selectivity, efficacy, and translational potential of photodynamic therapy (PDT). By integrating photosensitizers (PSs) with carbohydrates, amino acids, peptides, aptamers, proteins, cofactors, vitamins or antibodies, these constructs overcome long-standing [...] Read more.
Biomolecule–photosensitizer conjugates have rapidly evolved into one of the most powerful strategies for improving the selectivity, efficacy, and translational potential of photodynamic therapy (PDT). By integrating photosensitizers (PSs) with carbohydrates, amino acids, peptides, aptamers, proteins, cofactors, vitamins or antibodies, these constructs overcome long-standing limitations of classical PDT, including poor solubility, insufficient tumour accumulation, and strong dependence on oxygen availability. Beyond enhancing receptor-mediated uptake and enabling precise interactions with the tumour microenvironment (TME), bioconjugation also modulates aggregation, photochemical properties, intracellular accumulation, and immune system activation. A particularly transformative trend is the emergence of supramolecular architectures in which photosensitizers form defined nanostructured aggregates with peptides or proteins. Once considered an undesirable phenomenon, aggregation is now recognized as a tenable feature that governs photochemical behaviour. Engineered aggregates can undergo environment-triggered disassembly to monomeric, photoactive states, or operate as semiconductor-like nanodomains capable of Type I reaction through symmetry-breaking charge separation. This shift toward oxygen-independent radical pathways offers a promising solution to the challenge of hypoxia, a hallmark of the TME that severely compromises conventional Type II PDT. Parallel advances in 3D experimental platforms such as tumour organoids and organ-on-chip systems provide physiologically relevant validation of these conjugates, enabling the assessment of penetration, subcellular localization, immunogenic cell death, and therapeutic synergy within realistic TME conditions. Collectively, the integration of biomolecular targeting with controlled supramolecular design is redefining the landscape of PDT. Future progress will depend on designing conjugates that retain high activity under hypoxia, engineering dynamic aggregate states, and systematically validating these systems in advanced TME-mimetic models. Together, these developments position biomolecule–photosensitizer conjugates as a versatile and increasingly less oxygen-dependent class of next-generation phototherapeutic agents. Full article
(This article belongs to the Collection Feature Review Collection in Biopharmaceuticals)
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15 pages, 953 KB  
Article
Synthesis and Application of a Glucoconjugated Organometallic Rhenium Complex as an IR Imaging Probe for Glycolytic Cancer Cells
by Giulia Bononi, Erica Paltrinieri, Serena Fortunato, Gaspare Cicio, Nicola Di Giovanni, Giulia Lencioni, Niccola Funel, Elisa Giovannetti, Carlotta Granchi, Valeria Di Bussolo and Filippo Minutolo
Molecules 2026, 31(1), 28; https://doi.org/10.3390/molecules31010028 - 22 Dec 2025
Viewed by 592
Abstract
Current tumor diagnostics rely on fluorodeoxyglucose (FDG)-PET imaging, but FDG’s short half-life and high cost limit its widespread use. Infrared (IR) probes are emerging as non-radioactive alternatives to conventional tracers for tissue section and other in vitro imaging applications. Because cells and tissues [...] Read more.
Current tumor diagnostics rely on fluorodeoxyglucose (FDG)-PET imaging, but FDG’s short half-life and high cost limit its widespread use. Infrared (IR) probes are emerging as non-radioactive alternatives to conventional tracers for tissue section and other in vitro imaging applications. Because cells and tissues are relatively free of absorption peaks between 1800 and 2200 cm−1, metal-carbonyl complexes, especially cyclopentadienylrhenium(I) tricarbonyl (Cp[Re(CO)3]) derivatives, absorb strongly in this window and provide robust platforms for bioconjugation. Furthermore, Cp[Re(CO)3] fragments can be introduced into organic substrates via an elegant three-component reaction that simultaneously forges the cyclopentadienyl-metal and cyclopentadienyl-substituent bonds. As a result, the functionalized half-sandwich complex is obtained in a single step without any special handling issues. We have therefore properly modified a glucose molecule with that complex and developed a novel glucoconjugated Cp[Re(CO)3] probe that enables IR-based visualization of diseased cells at 2100 cm−1, offering a non-invasive, non-radioactive histological tool and a promising basis for future medical imaging devices. Full article
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13 pages, 1660 KB  
Article
Enhancement of Structural Stability and IgG Affinity of a Z34C-Derived α-Helical Peptide via Lactam Stapling
by Jung Gu Lee, Inseo Lee, Joo-young Kim, Suin Kim, Woo-jin Jeong and Ji-eun Kim
Antibodies 2025, 14(4), 108; https://doi.org/10.3390/antib14040108 - 16 Dec 2025
Viewed by 774
Abstract
Background: The Fc region of immunoglobulin G (IgG) is a key target in therapeutic and analytical applications, such as antibody purification and site-specific bioconjugation. Although Protein A exhibits strong Fc-binding affinity, its large molecular weight and limited chemical flexibility pose challenges for use [...] Read more.
Background: The Fc region of immunoglobulin G (IgG) is a key target in therapeutic and analytical applications, such as antibody purification and site-specific bioconjugation. Although Protein A exhibits strong Fc-binding affinity, its large molecular weight and limited chemical flexibility pose challenges for use in compact or chemically defined systems. To address these limitations, we designed two α-helical peptides, SpA h1 and SpA h2, based on the Fc-binding helices of the Z34C domain from Staphylococcus aureus Protein A. Method: To enhance the structural stability and Fc-binding capability of these peptides, a lactam-based stapling strategy was employed by introducing lysine and glutamic acid residues at positions i and i + 4. Result: The resulting stapled peptides, (s)SpA h1 and (s)SpA h2, exhibited significantly improved α-helical content and IgG-binding performance, as demonstrated by circular dichroism (CD) spectroscopy and fluorescence-based IgG capture assays. Surface plasmon resonance (SPR) analysis confirmed specific, concentration-dependent interactions with the Fc region of human IgG, with (s)SpA h1 consistently showing the binding affinity and stability. Proteolytic resistance assays using α-chymotrypsin revealed that (s)SpA h1 maintained its structural integrity over time, exhibiting markedly enhanced resistance to enzymatic degradation compared to its linear counterpart. Furthermore, (s)SpA h1 exhibited strong Fc selectivity with minimal Fab affinity, confirming its suitability as a compact and Fc-specific binding ligand. Conclusions: These results confirm the successful design and development of structurally reinforced Fc-binding peptides that overcome the inherent limitations of short linear sequences through both high-affinity sequence optimization and lactam-based stapling. Among them, (s)SpA h1 demonstrates the most promising characteristics as a compact yet stable Fc-binding ligand, suitable for applications such as antibody purification and site-specific bioconjugation. Full article
(This article belongs to the Section Antibody Discovery and Engineering)
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26 pages, 1651 KB  
Article
Synthesis of Bioconjugation Reagents for Use in Covalent Cross-Linking of Proteins by Azide-Alkyne Cycloaddition
by Nadja Suhorepec, Luka Ciber, Uroš Grošelj, Nejc Petek, Bogdan Štefane, Marko Novinec and Jurij Svete
Molecules 2025, 30(23), 4623; https://doi.org/10.3390/molecules30234623 - 2 Dec 2025
Viewed by 960
Abstract
A series of azide- and cyclooctyne-functionalized N-hydroxysuccinimidyl esters (NHS esters) and benzotriazolides were prepared and used as N-acylation reagents to obtain azide-(BSA-1) and cyclooctyne-functionalized bovine serum albumin proteins (BSA-2), fluorescein derivatives 5 and 6, and homobifunctional linkers [...] Read more.
A series of azide- and cyclooctyne-functionalized N-hydroxysuccinimidyl esters (NHS esters) and benzotriazolides were prepared and used as N-acylation reagents to obtain azide-(BSA-1) and cyclooctyne-functionalized bovine serum albumin proteins (BSA-2), fluorescein derivatives 5 and 6, and homobifunctional linkers 3 and 4. Strain-promoted azide-alkyne cycloaddition (SPAAC) and copper-catalyzed azide-alkyne cycloaddition (CuAAC) of azide-functionalized fluorescent probe 5 and alkyne-functionalized fluorescent probe 6 with complementary functionalized proteins BSA-2 and BSA-1 yielded fluorescent cycloadducts BSA-2-5 and BSA-1-6. These cycloadducts were used to determine the loading of BSA-1 and BSA-2 with the respective azido and cyclooctyne groups based on their molar absorbances and fluorescence intensities. Dimerization through covalent cross-linking of BSA was then performed by SPAAC between azide-functionalized BSA-1 and cyclooctyne-functionalized BSA-2, and by treating BSA-1 and BSA-2 with 0.5 equiv. of complementary bis-cyclooctyne linker 4 and bis-azide linker 3. Although the formation of covalent dimers BSA-1-2-BSA, BSA-1-6-1-BSA, and BSA-2-5-2-BSA was detected by SDS-PAGE analysis, this was a minor process, and most of the functionalized BSA did not form covalent dimers. Full article
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19 pages, 3512 KB  
Article
Biotin-Linked Ursolic Acid Conjugates as Selective Anticancer Agents and Target-Identification Tools for Cancer Therapy
by Riham M. Bokhtia, Kunj Bihari Gupta, Annabella Natalini, Theerth Vikas Srinivasan, Nihal Amineni, Sophia Ying, Rajeev Shakuja, Guido F. Verbeck, Bal L. Lokeshwar and Siva S. Panda
Molecules 2025, 30(23), 4588; https://doi.org/10.3390/molecules30234588 - 28 Nov 2025
Cited by 1 | Viewed by 694
Abstract
Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid, exhibits potent anticancer properties; however, its poor solubility and bioavailability limit its therapeutic application. To overcome these challenges and facilitate molecular target identification, a set of biotin-conjugated UA derivatives (5ad) was [...] Read more.
Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid, exhibits potent anticancer properties; however, its poor solubility and bioavailability limit its therapeutic application. To overcome these challenges and facilitate molecular target identification, a set of biotin-conjugated UA derivatives (5ad) was synthesized through selective C-28 alkylation and biotinylation. The use of microwave-assisted synthesis significantly enhanced both reaction efficiency and product purity. Among the derivatives, compound 5c exhibited increased cytotoxicity and selectivity against bladder cancer cell lines, surpassing UA in its ability to induce apoptosis, generate reactive oxygen species (ROS), and halt cell cycle progression at the G1 phase. Proteomic profiling revealed that 5c interacts with proteins involved in ER stress, RNA processing, cytoskeletal remodeling, and metabolic regulation. These findings underscore the potential of biotinylated UA derivatives as multifunctional chemical probes for mechanistic studies in the development of targeted therapies for cancer. Full article
(This article belongs to the Special Issue Natural Compounds in Modern Therapies, 2nd Edition)
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23 pages, 921 KB  
Review
Nano-Engineered Sensor Systems for Disease Diagnostics: Advances in Smart Healthcare Applications
by Tianjun Ma, Jianhai Sun, Ning Xue, Jamal N. A. Hassan and Adeel Abbas
Biosensors 2025, 15(12), 777; https://doi.org/10.3390/bios15120777 - 26 Nov 2025
Cited by 2 | Viewed by 1657
Abstract
Nano-engineered sensor systems represent a paradigm shift in disease diagnostics, offering unprecedented capabilities for precision medicine. This review methodically evaluates these advanced platforms, consolidating recent advancements across four critical clinical domains: diabetes monitoring, cancer detection, infectious disease diagnostics and cardiac/genetic health. We demonstrate [...] Read more.
Nano-engineered sensor systems represent a paradigm shift in disease diagnostics, offering unprecedented capabilities for precision medicine. This review methodically evaluates these advanced platforms, consolidating recent advancements across four critical clinical domains: diabetes monitoring, cancer detection, infectious disease diagnostics and cardiac/genetic health. We demonstrate how the unique properties of nanomaterials, such as graphene, quantum dots and plasmonic nanoparticles, are being harnessed to achieve remarkable gains in analytical sensitivity, selectivity and real-time monitoring. Specific breakthroughs include graphene-based sensors attaining clinically significant limits for continuous glucose monitoring, quantum dot bioconjugates enabling ultrasensitive imaging of cancer biomarkers and surface-enhanced Raman spectroscopy (SERS) probes facilitating early tumor identification. Furthermore, nanosensors exhibit exceptional precision in detecting viral antigens and genetic mutations, underscoring their robust translational potential. Collectively, these developments signal a clear trajectory toward integrated, intelligent healthcare ecosystems. However, for these promising technologies to transition into accessible and cost-effective diagnostic solutions, persistent challenges in scalability, manufacturing reproducibility and long-term biocompatibility must be addressed through continued interdisciplinary innovation. Full article
(This article belongs to the Special Issue Recent Advances in Biosensing Technologies for Single Cell Analysis)
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17 pages, 2595 KB  
Article
Synthesis of Carboxymethyl Dextran-Coated Gold Nanoparticles as Stable and Storable Optical Labels for Ultrasensitive Plasmonic Nanoparticle-Linked Sorbent Assay
by Novi Asri Sitinjak, Chien-Wei Huang, Tsung-Yi Yang, Lai-Kwan Chau and Chih-Hsien Wang
Sensors 2025, 25(23), 7156; https://doi.org/10.3390/s25237156 - 24 Nov 2025
Cited by 1 | Viewed by 579
Abstract
Gold nanoparticles (AuNPs) are widely employed in biosensors; however, conventional synthesis methods require additional surface modification to confer colloidal stability and bioconjugation capability. Here, we report a facile strategy to synthesize carboxymethyl dextran (CMD)-coated AuNPs (AuNP@CMD) that simultaneously serve as a plasmonic label, [...] Read more.
Gold nanoparticles (AuNPs) are widely employed in biosensors; however, conventional synthesis methods require additional surface modification to confer colloidal stability and bioconjugation capability. Here, we report a facile strategy to synthesize carboxymethyl dextran (CMD)-coated AuNPs (AuNP@CMD) that simultaneously serve as a plasmonic label, a stabilizing agent, and a functional scaffold. The CMD was prepared directly via partial carboxymethylation of dextran in a one-pot reduction of HAuCl4, enabling the synthesis of AuNP@CMD with tunable particle sizes and excellent colloidal stability for at least one month at 4 °C. The CMD coating on AuNPs can prevent nanoparticle aggregation, suppress nonspecific adsorption, and introduce surface carboxyl groups for conjugation of bioprobes. Such characteristics are important to develop plasmonic nanoparticle-linked sorbent assays as an alternative to the conventional colorimetric enzyme-linked immunosorbent assay. When applied to a fiber-optic nanogold-linked sorbent assay, AuNP@CMD enabled ultrasensitive detection of a single-stranded DNA, achieving a detection limit at the femtomolar (fM) concentration level without nucleic acid amplification. Full article
(This article belongs to the Special Issue Biosensor Technologies Based on Nanomaterials)
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42 pages, 15838 KB  
Review
Progress in the Design and Application of Chemical and Biological Sensors Based on Atom Transfer Radical Polymerization
by Ning Xia, Fengli Gao, Zhaojiang Yu, Shuaibing Yu and Xinyao Yi
Biosensors 2025, 15(11), 752; https://doi.org/10.3390/bios15110752 - 10 Nov 2025
Viewed by 1160
Abstract
Atom transfer radical polymerization (ATRP) is a leading reversible deactivation radical polymerization method. It has become an emerging technology to synthesize well-defined, tailor-made polymers, promoting the development of advanced materials (e.g., bioconjugates and nanocomposites) with precisely designed and controlled macromolecular architectures. ATRP-produced polymers [...] Read more.
Atom transfer radical polymerization (ATRP) is a leading reversible deactivation radical polymerization method. It has become an emerging technology to synthesize well-defined, tailor-made polymers, promoting the development of advanced materials (e.g., bioconjugates and nanocomposites) with precisely designed and controlled macromolecular architectures. ATRP-produced polymers or polymeric materials have been successfully applied in the fields of drug delivery, tissue engineering, sample separation, environmental monitoring, bioimaging, clinical diagnostics, etc. In this review, we systematically summarize the progress of ATRP-based chemical and biological sensors in different application fields, including ion sensing, small-molecule detection, bioimaging, and signal amplification for biosensors. Finally, we briefly outline the prospects and future directions of ATRP. This review is expected to provide a fundamental and timely understanding of ATRP-based sensors and guide the design of novel materials and methods for sensing applications. Full article
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12 pages, 1500 KB  
Article
Linker-Engineered Tyrosine–Azide Coatings for Stable Strain-Promoted Azide–Alkyne Cycloaddition (SPAAC) Functionalization
by Suho Park, Himani Bisht, Jiwoo Park, Seongchul Park, Yubin Hong, Daeun Chu, Minseob Koh, Hojae Lee and Daewha Hong
Polymers 2025, 17(22), 2969; https://doi.org/10.3390/polym17222969 - 7 Nov 2025
Viewed by 3135
Abstract
Strain-promoted azide–alkyne cycloaddition (SPAAC) is widely used in solution-phase bioconjugation. However, its application in surface chemistry remains limited because substrate-independent azide films that remain stable upon reaction with bulky strained alkynes have not yet been developed. In this study, we address this challenge [...] Read more.
Strain-promoted azide–alkyne cycloaddition (SPAAC) is widely used in solution-phase bioconjugation. However, its application in surface chemistry remains limited because substrate-independent azide films that remain stable upon reaction with bulky strained alkynes have not yet been developed. In this study, we address this challenge using a melanin-inspired coating based on tyrosine–azide derivatives with different linkers. In particular, we investigated how differences in linker length and hydrophilicity affect the hydrophobic interactions within the film network and, ultimately, determine film stability. Specifically, Tyr-3-N3, a tyrosine–azide derivative having an azide group tethered to tyrosine through a short three-carbon alkyl linker, was identified as optimal, forming azide-presenting films via tyrosinase-mediated oxidation and retaining integrity during SPAAC with external dibenzocyclooctyne (DBCO) ligands. The optimized poly(Tyr-3-N3) coatings enabled efficient methoxypolyethylene glycol (mPEG) immobilization, thereby exhibiting excellent antifouling performance against protein adsorption, and further supported spatially controlled protein patterning through soft lithography techniques such as micromolding in capillaries (MIMIC) and microcontact printing (µCP). The approach was broadly applicable with a range of inorganic and polymeric substrates, as well as living cell surfaces; even after encapsulation and SPAAC-based functionalization, the cells remained viable. Collectively, these findings establish a substrate-independent and biocompatible coating platform that preserves film stability through SPAAC functionalization, supporting applications in antifouling coatings, biosensing, and cell surface engineering. Full article
(This article belongs to the Section Polymer Chemistry)
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