Philipp Zimmermann, Peter Schulze, Annette G Beck-Sickinger, Yuliya Khrunyk
{"title":"Design and Biofunctionalization of Cloud Sponge-Inspired Scaffolds for Enhanced Bone Cell Performance.","authors":"Philipp Zimmermann, Peter Schulze, Annette G Beck-Sickinger, Yuliya Khrunyk","doi":"10.1021/acsabm.4c01065","DOIUrl":"10.1021/acsabm.4c01065","url":null,"abstract":"<p><p>With the increasing age of our population, which is linked to a higher incidence of musculoskeletal diseases, there is a massive clinical need for bone implants. Porous scaffolds, usually offering a lower stiffness and allowing for the ingrowth of blood vessels and nerves, serve as an attractive alternative to conventional implants. Natural porous skeletons from marine sponges represent an array of evolutionarily optimized patterns, inspiring the design of biomaterials. In this study, cloud sponge-inspired scaffolds were designed and printed from a photocurable polymer, Clear Resin. These scaffolds were biofunctionalized by mussel-derived peptide MP-RGD, a recently developed peptide that contains a cyclic, bioactive RGD cell adhesion motif and catechol moieties, which provide the anchoring of the peptide to the surface. In <i>in vitro</i> cell culture assays with bone cells, significantly higher biocompatibility of three scaffolds, <i><i>i.e.</i></i>, square, octagon, and hexagon cubes, in comparison to hollow and sphere inside cubes was shown. The performance of the cells regarding signaling was further enhanced by applying an MP-RGD coating. Consequently, these data demonstrate that both the structure of the scaffold and the coating contribute to the biocompatibility of the material. Three out of five MP-RGD-coated sponge-inspired scaffolds displayed superior biochemical properties and might guide material design for improved bone implants.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"8281-8293"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mathieu Joos, Thijs Vackier, Maarten A Mees, Guglielmo Coppola, Stelios Alexandris, Robbe Geunes, Wim Thielemans, Hans P L Steenackers
{"title":"Antimicrobial Activity of Glycyrrhizinic Acid Is pH-Dependent.","authors":"Mathieu Joos, Thijs Vackier, Maarten A Mees, Guglielmo Coppola, Stelios Alexandris, Robbe Geunes, Wim Thielemans, Hans P L Steenackers","doi":"10.1021/acsabm.4c00942","DOIUrl":"10.1021/acsabm.4c00942","url":null,"abstract":"<p><p>In recent years, antimicrobial hydrogels have attracted much attention in biomedical applications due to their biocompatibility and high water content. Glycyrrhizin (GA) is an antimicrobial that can form pH-dependent hydrogels due to the three carboxyl groups of GA that differ in p<i>K</i><sub>a</sub> value. The influence of GA protonation on the antimicrobial activity, however, has never been studied before. Therefore, we investigated the effect of the pH on the antimicrobial activity of GA against <i>Pseudomonas aeruginosa</i>, <i>Staphylococcus aureus</i>, MRSA, <i>Staphylococcus epidermidis</i>, <i>Acinetobacter baumannii</i>, <i>Klebsiella pneumoniae</i>, <i>Klebsiella aerogenes</i>, and two strains of <i>Escherichia coli</i>. In general, the antimicrobial activity of GA increases as a function of decreasing pH (and thus increasing protonation of GA). More specifically, fully protonated GA hydrogels (pH = 3) are required for growth inhibition and killing of <i>E. coli</i> UTI89 and <i>Klebsiella</i> in the suspension above the hydrogel, while the staphylococci strains and <i>A. baumannii</i> are already inhibited by fully deprotonated GA (pH = 6.8). <i>P. aeruginosa</i> and <i>E. coli</i> DH5α showed moderate susceptibility, as they are completely inhibited by a hydrogel at pH 3.8, containing partly protonated GA, but not by fully deprotonated GA (pH = 6.8). The antimicrobial activity of the hydrogel cannot solely be attributed to the resulting pH decrease of the suspension, as the presence of GA significantly increases the activity. Instead, this increased activity is due to the release of GA from the hydrogel into the suspension, where it directly interacts with the bacteria. Moreover, we provide evidence indicating that the pH dependency of the antimicrobial activity is due to differences in GA protonation state by treating the pathogens with GA solutions differing in their GA protonation distribution. Finally, we show by LC-MS that there is no chemical or enzymatic breakdown of GA. Overall, our results demonstrate that the pH influences not only the physical but also the antimicrobial properties of the GA hydrogels.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"8223-8235"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haojie Wang, Rong Xu, Shuangyan She, Md Abdullah, Kai Meng, Miao Xiao, Jihua Nie, Huijing Zhao, Ke-Qin Zhang
{"title":"PTFE Stent Membrane Based on the Electrospinning Technique and Its Potential for Replacing ePTFE.","authors":"Haojie Wang, Rong Xu, Shuangyan She, Md Abdullah, Kai Meng, Miao Xiao, Jihua Nie, Huijing Zhao, Ke-Qin Zhang","doi":"10.1021/acsabm.4c01392","DOIUrl":"10.1021/acsabm.4c01392","url":null,"abstract":"<p><p>Expanded poly(tetrafluoroethylene) (ePTFE), obtained by the paste extrusion-stretching method, is a commonly used stent membrane material for the treatment of arterial stenosis or aneurysm in clinical practice. However, the structure of ePTFE is nonfibrous, which is not friendly to cells, and the equipment consumes a lot of energy and often requires the use of flammable and toxic lubricants. In this study, electrospinning was used to prepare PTFE vascular stent membranes, following plasma treatment, dopamine, and heparin grafting to obtain an anticoagulant surface. The morphology, structure, axial and circumferential tensile strength, porosity, water penetration pressure, and heparin-releasing behaviors of the samples were studied at first. Then, the experiments of blood compatibility, cytotoxicity, and <i>in vivo</i> subcutaneous implantation were conducted. Results showed that the PTFE electrospun tubular membrane has submicrometer to nanoscale fiber structures similar to the extracellular matrix. The axial and circumferential tensile strengths can reach 8.12 and 6.10 MPa, respectively, and the axial and circumferential elongations at break can reach 328.75% and 285.28%, respectively. It maintains higher porosity and water penetration pressure as well as a longer heparin-releasing period. It has a suitable hemolysis rate and superior anticoagulant properties. Dopamine and heparin modifications can facilitate the adhesion and proliferation of endothelial cells. Histological analysis of the PTFE electrospun tubular membrane showed no difference from the commercially available ePTFE graft.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"8608-8620"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Photothermally Active Quantum Dots in Cancer Imaging and Therapeutics: Nanotheranostics Perspective.","authors":"Monalisha Debnath, Sayoni Sarkar, Sujit Kumar Debnath, Daphika S Dkhar, Rohini Kumari, Geetha Satya Sainaga Jyothi Vaskuri, Ananya Srivastava, Pranjal Chandra, Rajendra Prasad, Rohit Srivastava","doi":"10.1021/acsabm.4c01190","DOIUrl":"10.1021/acsabm.4c01190","url":null,"abstract":"<p><p>Cancer is becoming a global threat, as the cancerous cells manipulate themselves frequently, resulting in mutants and more abnormalities. Early-stage and real-time detection of cancer biomarkers can provide insight into designing cost-effective diagnostic and therapeutic modalities. Nanoparticle and quantum dot (QD)-based approaches have been recognized as clinically relevant methods to detect disease biomarkers at the molecular level. Over decades, as an emergent noninvasive approach, photothermal therapy has evolved to eradicate cancer. Moreover, various structures, viz., nanoparticles, clusters, quantum dots, etc., have been tested as bioimaging and photothermal agents to identify tumor cells selectively. Among them, QDs have been recognized as versatile probes. They have attracted enormous attention for imaging and therapeutic applications due to their unique colloidal stability, optical and physicochemical properties, biocompatibility, easy surface conjugation, scalable production, etc. However, a few critical concerns of QDs, viz., precise engineering for molecular imaging and sensing, selective interaction with the biological system, and their associated toxicity, restrict their potential intervention in curing cancer and are yet to be explored. According to the U.S. Food and Drug Administration (FDA), there is no specific regulation for the approval of nanomedicines. Therefore, these nanomedicines undergo the traditional drug, biological, and device approval process. However, the market survey of QDs is increasing, and their prospects in translational nanomedicine are very promising. From this perspective, we discuss the importance of QDs for imaging, sensing, and therapeutic usage pertinent to cancer, especially in its early stages. Moreover, we also discuss the rapidly growing translational view of QDs. The long-term safety studies and cellular interaction of these QDs could enhance their visibility and bring photothermally active QDs to the clinical stage and concurrently to FDA approval.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"8126-8148"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142636223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advances in Injectable Polymeric Biomaterials and Their Contemporary Medical Practices.","authors":"Sophia Beilharz, Mithun Kumar Debnath, Daniele Vinella, Andrew J Shoffstall, Metin Karayilan","doi":"10.1021/acsabm.4c01001","DOIUrl":"10.1021/acsabm.4c01001","url":null,"abstract":"<p><p>Injectable biomaterials have been engineered to operate within the human body, offering versatile solutions for minimally invasive therapies and meeting several stringent requirements such as biocompatibility, biodegradability, low viscosity for ease of injection, mechanical strength, rapid gelation postinjection, controlled release of therapeutic agents, hydrophobicity/hydrophilicity balance, stability under physiological conditions, and the ability to be sterilized. Their adaptability and performance in diverse clinical settings make them invaluable for modern medical treatments. This article reviews recent advancements in the design, synthesis, and characterization of injectable polymeric biomaterials, providing insights into their emerging applications. We discuss a broad spectrum of these materials, including natural, synthetic, hybrid, and composite types, that are being applied in targeted drug delivery, cell and protein transport, regenerative medicine, tissue adhesives, injectable implants, bioimaging, diagnostics, and 3D bioprinting. Ultimately, the review highlights the critical role of injectable polymeric biomaterials in shaping the future of medical treatments and improving patient outcomes across a wide range of therapeutic and diagnostic applications.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"8076-8101"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"l-Cystine-Based Polyurethane as a Drug-Delivery Vehicle in Targeted Cancer Therapy and Biomedical Applications.","authors":"Sudepta Bauri, Pravesh Kumar Yadav, Avishek Mallick Choudhury, Pralay Maiti","doi":"10.1021/acsabm.4c01479","DOIUrl":"10.1021/acsabm.4c01479","url":null,"abstract":"<p><p>Controlled and sustained drug release is a critical aspect of drug-delivery systems (DDSs) that can be used in chemotherapy while ensuring therapy effectiveness and biosafety. Hence, polyurethane (PU) is modified using a biomolecule Cystine (CYS) for protracted drug release, aiming to enhance cancer treatment efficacy while minimizing adverse side effects in tumor patients. To confirm the formation of a polymer structure, characterization techniques such as NMR and FTIR are used, and the morphology is determined using SEM. Biocompatibility of the synthesized polymers is evaluated through cellular assessments, including MTT assay, cell adhesion, and antibacterial assay along with drug release using an anticancer drug, Paclitaxel (PTX). Notably, the incorporation of PTX in the polymer matrix results in minimal mortality (85% viable cells) rates in healthy cells (3T3), in contrast to a 56% mortality rate observed with the pure drug. While PTX shows a burst release and kills cancer cells only for the first 24 h, PU loaded with the drug shows sustained release and kills the cancer cells for 3 days. This vehicle selectively kills 59% of SiHA cells after a consecutive study of 3 days, which highlights the potential of this newly designed vehicle for effective drug delivery, particularly in anticancer treatments. Moreover, cystine's antibacterial property adds up with PU; hence, PU shows antibacterial activity against <i>Staphylococcus aureus</i> (MIC, 20 μg/mL) and also acts as a reductive oxygen species scavenger. Therefore, modifying PU with CYS has shown sustained release of PTX along with a selective effect on cells, underscoring its significance as a superior delivery agent and supported by a shred of convincing evidence.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"8671-8684"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jooho Jung, Marin Eguchi, Shintaro Ida, Kai Kamada
{"title":"Sustainable Antibacterial Surface of Transparent PMMA Membranes with α-ZrP Nanosheets Adsorbing Tetraalkylammonium Ions.","authors":"Jooho Jung, Marin Eguchi, Shintaro Ida, Kai Kamada","doi":"10.1021/acsabm.4c01342","DOIUrl":"10.1021/acsabm.4c01342","url":null,"abstract":"<p><p>We fabricated composite membranes containing inorganic nanosheets (NSs) and polymers and demonstrated their outstanding antibacterial performance against several opportunistic pathogens. Layered α-zirconium phosphate [Zr(HPO<sub>4</sub>)<sub>2</sub>, α-ZrP] as a pristine compound of NS was exfoliated by ion-exchanging protons in the interlayer space of α-ZrP with bulky tetraalkylammonium ions (TRA<sup>+</sup>: R = butyl, hexyl, and octyl). During the exfoliation process, TRA<sup>+</sup> was electrostatically adsorbed onto α-ZrP NS with a negative surface charge (ZrP-TRA-NS). The produced PMMA membrane including α-ZrP NS (PM-ZrP-TRA-NS) was optically transparent and prohibited bacterial growth, and the effect was stronger for Gram-positive <i>Staphylococcus aureus</i> than Gram-negative <i>Escherichia coli</i>. The antibacterial activity of PM-ZrP-TRA-NS was based on physical damage induced by both 2D ceramic NSs and sharp alkyl chains of TRA<sup>+</sup>. Despite the inherent flexibility of alkyl chains, when adsorbed onto the NSs, they can act in a manner that effectively pierces the bacterial cell wall. The piercing force of TRA<sup>+</sup> was greater for the longer alkyl chains (TBA<sup>+</sup> < THA<sup>+</sup> < TOA<sup>+</sup>). Focusing on the difference in the cell wall structure between these bacteria, the growth of Gram-positive <i>S. aureus</i> with loose peptidoglycan layers as an outer membrane could be easily inhibited by contact with the composite film. In contrast, Gram-negative bacteria <i>E. coli</i>, surrounded by a relatively dense outer cell wall composed of peptidoglycan and lipopolysaccharide layers, could not be damaged easily. In this study, the antibacterial mechanism of PM-ZrP-TRA-NS membranes was elucidated, and their usefulness as antimicrobial coatings for existing solid surfaces was demonstrated.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"8590-8598"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sergio J Peñas-Núñez, David Mecerreyes, Miryam Criado-Gonzalez
{"title":"Recent Advances and Developments in Injectable Conductive Polymer Gels for Bioelectronics.","authors":"Sergio J Peñas-Núñez, David Mecerreyes, Miryam Criado-Gonzalez","doi":"10.1021/acsabm.3c01224","DOIUrl":"10.1021/acsabm.3c01224","url":null,"abstract":"<p><p>Soft matter bioelectronics represents an emerging and interdisciplinary research frontier aiming to harness the synergy between biology and electronics for advanced diagnostic and healthcare applications. In this context, a whole family of soft gels have been recently developed with self-healing ability and tunable biological mimetic features to act as a tissue-like space bridging the interface between the electronic device and dynamic biological fluids and body tissues. This review article provides a comprehensive overview of electroactive polymer gels, formed by noncovalent intermolecular interactions and dynamic covalent bonds, as injectable electroactive gels, covering their synthesis, characterization, and applications. First, hydrogels crafted from conducting polymers (poly(3,4-ethylene-dioxythiophene) (PEDOT), polyaniline (PANi), and polypyrrole (PPy))-based networks which are connected through physical interactions (e.g., hydrogen bonding, π-π stacking, hydrophobic interactions) or dynamic covalent bonds (e.g., imine bonds, Schiff-base, borate ester bonds) are addressed. Injectable hydrogels involving hybrid networks of polymers with conductive nanomaterials (i.e., graphene oxide, carbon nanotubes, metallic nanoparticles, etc.) are also discussed. Besides, it also delves into recent advancements in injectable ionic liquid-integrated gels (iongels) and deep eutectic solvent-integrated gels (eutectogels), which present promising avenues for future research. Finally, the current applications and future prospects of injectable electroactive polymer gels in cutting-edge bioelectronic applications ranging from tissue engineering to biosensing are outlined.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"7944-7964"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139745591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biocompatible Triboelectric Nanogenerators for Self-Powered Microelectronics: Design, Performance, and Real-Time Applications.","authors":"Karthikeyani Ramesh, Sasirekha Venkidusamy, Ponniah Vajeeston, Ragavendran Venkatesan, Jeyanthinath Mayandi","doi":"10.1021/acsabm.4c01414","DOIUrl":"10.1021/acsabm.4c01414","url":null,"abstract":"<p><p>In the present study, we demonstrated a cost-effective chia seed-based triboelectric nanogenerator (C-TENG), leveraging the triboelectric properties of chia seeds. The C-TENGs are fabricated with a simple architecture, establishing adaptability, cost effectiveness, and versatility as an ecofriendly harvester of mechanical energy. The C-TENG exhibits open- circuit voltage and short-circuit currents on the order of 501.8 V and 24.5 μA, respectively. Load matching reveals the maximum power density output at a load resistance of 5 MΩ, reaching 290 mW/m<sup>2</sup>. The cycle test over 3400 cycles confirms the C-TENG's stability. Furthermore, its capability to charge capacitors with different capacitances highlights its potential as a biomechanical energy harvester. The prototype device for evaluating the real-time applications demonstrated the C-TENG's, ability to illuminate LEDs, power a calculator, capture kinetic energy during walking, and transducer as an electronic switch. This investigation pioneered the exploration of chia seeds in TENGs, presenting a sustainable and efficient solution for self-powered microelectronic devices. The electron affinity of materials has been analyzed through inter- and intramolecular charge distribution using density functional theory. The direction of charge transfer was estimated through frontier molecular orbital analysis supported by the experimental findings of triboelectrification via contact separation from the molecule to polytetrafluoroethylene (PTFE).</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"8621-8631"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mahmood Norouzi, Adonis Amoli, Yang Zhang, Yan Zhang, Ashlyn Colleen Beatty, Anna Jarvi, Athar Ata, Thomas Werner, Haiying Liu
{"title":"Deep-Red and Near-Infrared Compact Cyanine Dyes for Sensitive NAD(P)H Sensing in Live Cells and Kidney Disease Tissues.","authors":"Mahmood Norouzi, Adonis Amoli, Yang Zhang, Yan Zhang, Ashlyn Colleen Beatty, Anna Jarvi, Athar Ata, Thomas Werner, Haiying Liu","doi":"10.1021/acsabm.4c01345","DOIUrl":"10.1021/acsabm.4c01345","url":null,"abstract":"<p><p>Cyanine dyes constructed for NAD(P)H near-infrared sensing utilize extended π-conjugation but often exhibit delayed fluorescence responses to NAD(P)H due to reduced positive charge density in 3-quinolinium acceptors. This study introduces deep-red and near-infrared compact cyanine dyes represented by probes <b>A</b> and <b>B</b> for mitochondrial NAD(P)H detection in live cells. Probes <b>A</b> and <b>B</b> feature a unique structural design with a double bond connection linking 3-quinolinium to strategically positioned 1-methylquinolinium acceptor units at 2- and 4-positions, correspondingly. Probe <b>A</b> absorbs at 359 and 531 nm, while probe <b>B</b> absorbs at 324 and 370 nm, emitting subtle fluorescence at 587 and 628 nm, respectively, with no NADH present. Upon NADH exposure, probes <b>A</b> and <b>B</b> exhibit significant emission enhancements at 612 and 656 nm, correspondingly, attributed to the efficient reduction of 3-quinolinium units to electron-donative 1-methyl-1,4-dihydroquinoline units. Probe <b>B</b>, chosen for its near-infrared emission and fast response to NAD(P)H, effectively monitored dynamic intracellular NAD(P)H levels throughout diverse experimental conditions. In HeLa cells, minimal basal fluorescence increased upon NADH stimulation. It also identified increased NAD(P)H levels following chemical treatments with acesulfame potassium, cisplatin, carboplatin, and temozolomide, CoCl<sub>2</sub>-induced hypoxia, and TLR4 activation in macrophages and in disease models of kidney pathology, where diseased tissues exhibited higher fluorescence than normal tissues. In fruit fly larvae under starvation conditions, probe <b>B</b> tracked NAD(P)H increases triggered by exogenous NADH, demonstrating its in vivo applicability for metabolic studies. These findings highlight probe <b>B</b>'s utility in elucidating dynamic NAD(P)H fluctuations in diverse biological contexts, offering insights into mitochondrial function and cellular metabolism.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"8552-8564"},"PeriodicalIF":4.6,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142724272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}