This study investigates the multifunctional potential of ZnO/CuO/Clay heterojunction nanocomposites (NCs) synthesized via the solution combustion method. Six NCs were prepared by varying ZnO/CuO ratios within two clay molar fractions (0.25 and 0.5 mol). Structural and compositional analyses (field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), inductively coupled plasma optical emission spectroscopy (ICP-OES), dynamic light scattering (DLS), and Brunauer–Emmett–Teller (BET)) confirmed successful heterojunction formation, uniform elemental distribution, stable colloidal behavior, and a mesoporous nanostructure. Ultraviolet-visible diffuse reflectance spectroscopy (UV–vis DRS) revealed enhanced visible-light absorption with increasing CuO and decreasing clay content, thereby improving the NC’s optical characteristics and resulting in enhanced photocatalytic performance. Band gap measurements revealed CuO’s band gap narrowing effect, while ZnO and clay increased it. Antibacterial assays against Escherichia coli and Staphylococcus aureus showed significantly enhanced activity, with lower MIC values observed for NCs containing 0.25 mol clay. This behavior can be attributed to the smaller particle size, improved nanoparticle (NP) dispersion, reduced aggregation, increased porosity, and greater active surface area of these NCs compared to those with 0.5 mol clay. Transmission electron microscopy (TEM) imaging confirmed membrane disruption as a key antibacterial mechanism, supported by reactive oxygen species (ROS) generation, ion release, and synergistic interaction with clay nanosheets. Cytotoxicity tests on cancerous HT-29 cells demonstrated dose- and time-dependent behavior for the 0.75CuO/0.25Clay NC and dose-dependent behavior for the 0.75ZnO/0.25Clay NC, both with minimal toxicity to normal HFF cells. Antioxidant evaluation showed significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (57%), comparable to ascorbic acid (60.2%). Overall, these results highlight solution combustion-synthesized ZnO/CuO/Clay NCs as promising bioactive materials for photocatalytic, antibacterial, anticancer, and antioxidant applications in medicine, food packaging, and environmental remediation.
{"title":"Synergistic Mechanisms Underlying Optical, Antimicrobial, Anticancer, and Antioxidant Activities of Multifunctional Bioactive ZnO/CuO/Clay Nanocomposites","authors":"Setareh Khosrovan, , , Jalil Vahdati Khaki, , , Mostafa Mirjalili*, , , Maryam M. Matin, , and , Naeemeh Esfandiari, ","doi":"10.1021/acsabm.5c01884","DOIUrl":"10.1021/acsabm.5c01884","url":null,"abstract":"<p >This study investigates the multifunctional potential of ZnO/CuO/Clay heterojunction nanocomposites (NCs) synthesized via the solution combustion method. Six NCs were prepared by varying ZnO/CuO ratios within two clay molar fractions (0.25 and 0.5 mol). Structural and compositional analyses (field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), inductively coupled plasma optical emission spectroscopy (ICP-OES), dynamic light scattering (DLS), and Brunauer–Emmett–Teller (BET)) confirmed successful heterojunction formation, uniform elemental distribution, stable colloidal behavior, and a mesoporous nanostructure. Ultraviolet-visible diffuse reflectance spectroscopy (UV–vis DRS) revealed enhanced visible-light absorption with increasing CuO and decreasing clay content, thereby improving the NC’s optical characteristics and resulting in enhanced photocatalytic performance. Band gap measurements revealed CuO’s band gap narrowing effect, while ZnO and clay increased it. Antibacterial assays against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> showed significantly enhanced activity, with lower MIC values observed for NCs containing 0.25 mol clay. This behavior can be attributed to the smaller particle size, improved nanoparticle (NP) dispersion, reduced aggregation, increased porosity, and greater active surface area of these NCs compared to those with 0.5 mol clay. Transmission electron microscopy (TEM) imaging confirmed membrane disruption as a key antibacterial mechanism, supported by reactive oxygen species (ROS) generation, ion release, and synergistic interaction with clay nanosheets. Cytotoxicity tests on cancerous HT-29 cells demonstrated dose- and time-dependent behavior for the 0.75CuO/0.25Clay NC and dose-dependent behavior for the 0.75ZnO/0.25Clay NC, both with minimal toxicity to normal HFF cells. Antioxidant evaluation showed significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (57%), comparable to ascorbic acid (60.2%). Overall, these results highlight solution combustion-synthesized ZnO/CuO/Clay NCs as promising bioactive materials for photocatalytic, antibacterial, anticancer, and antioxidant applications in medicine, food packaging, and environmental remediation.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"11190–11205"},"PeriodicalIF":4.7,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626928","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}
Sarah N. Wilson, , , Vijay Singh Gondil, , , Elizabeth J. Brisbois*, , and , Hitesh Handa*,
The ongoing threat of antimicrobial-resistant (AMR) bacteria and the growing population of AMR bacteria have inspired research into alternative antimicrobial agents. Previous studies have shown clinically relevant bactericidal effects of the molecule nitric oxide (NO). Not only has extensive research proven its antimicrobial effect, but bacteria have also been shown to be less likely to become resistant to NO. Numerous studies have also demonstrated that NO is compatible with commercially available antibiotic drugs, enhancing antimicrobial effects. However, these drugs are not always readily available or easily manufactured. This study proposes combining NO with naturally sourced antibacterial agents, namely bacteriophages. This combination of NO with bacteriophages in solution demonstrated an 82 ± 1.7% killing efficiency against its target pathogen, Escherichia coli, and a 74 ± 2.9% reduction in Methicillin-resistant Staphylococcus aureus throughout a 12 h growth curve, indicating significant potential for further development as a broad-spectrum antimicrobial combination therapy.
{"title":"Potential of Nitric Oxide and Bacteriophages as Combined Antibacterial Agents to Counter Drug-Resistant Infections","authors":"Sarah N. Wilson, , , Vijay Singh Gondil, , , Elizabeth J. Brisbois*, , and , Hitesh Handa*, ","doi":"10.1021/acsabm.5c01489","DOIUrl":"10.1021/acsabm.5c01489","url":null,"abstract":"<p >The ongoing threat of antimicrobial-resistant (AMR) bacteria and the growing population of AMR bacteria have inspired research into alternative antimicrobial agents. Previous studies have shown clinically relevant bactericidal effects of the molecule nitric oxide (NO). Not only has extensive research proven its antimicrobial effect, but bacteria have also been shown to be less likely to become resistant to NO. Numerous studies have also demonstrated that NO is compatible with commercially available antibiotic drugs, enhancing antimicrobial effects. However, these drugs are not always readily available or easily manufactured. This study proposes combining NO with naturally sourced antibacterial agents, namely bacteriophages. This combination of NO with bacteriophages in solution demonstrated an 82 ± 1.7% killing efficiency against its target pathogen, <i>Escherichia coli</i>, and a 74 ± 2.9% reduction in Methicillin-resistant <i>Staphylococcus aureus</i> throughout a 12 h growth curve, indicating significant potential for further development as a broad-spectrum antimicrobial combination therapy.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"10793–10799"},"PeriodicalIF":4.7,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsabm.5c01489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew Darnell*, , , D. S. Abdullah Al Maruf*, , , Eva Tomaskovic-Crook, , , Kai Cheng, , , William T. Lewin, , , Hai Xin, , , Hedi V. Kruse, , , Daniel K. Lawrence, , , Innes Wise, , , Aditi Gupta, , , David Leinkram, , , Timothy G. H. Manzie, , , Krishnan Parthasarathi, , , James Wykes, , , Catriona Froggatt, , , Gordon Wallace, , , David R. McKenzie, , , Jeremy M. Crook, , and , Jonathan R. Clark,
This protocol was developed to assess in vivo osteogenesis of 3D-printed, selectively polymerized β-tricalcium phosphate (SP-βTCP) scaffolds placed between the periosteum and native bone of sheep scapulae. The protocol spans the entire development process of scaffold design, infusion, implantation and explant analysis. 3D printed SP-βTCP scaffolds of variable pore size were infused with combinations of gelatin methacryloyl and autologous or allogeneic adipose-derived stem cells (ADSCs), and placed within plasma-treated polyetherketone bioreactor chambers manufactured by laser sintering. These were implanted for 12 weeks on the left sheep scapula and 16 weeks on the right, followed by explantation and scanning using micro computed tomography (μCT). Images were analyzed using Imalytics Preclinical software via six key steps: (i) experimental chamber selection, (ii) chamber isolation, (iii) scaffold thresholding, (iv) bone thresholding, (v) volume generation and (vi) verification. This protocol delineated the border between bone and scaffold material, allowing for reliable quantification of bone formation. ADSCs and scaffolds with a smaller pore size were associated with superior bone formation, regardless of cell origin. These results demonstrate the utility of this protocol in analyzing μCT images in situations where high-density biomaterials degrade at variable rates.
{"title":"Protocol for Micro Computed Tomography Quantification of Neo-osteogenesis in High Density Additively Manufactured Calcium Phosphate Scaffolds","authors":"Matthew Darnell*, , , D. S. Abdullah Al Maruf*, , , Eva Tomaskovic-Crook, , , Kai Cheng, , , William T. Lewin, , , Hai Xin, , , Hedi V. Kruse, , , Daniel K. Lawrence, , , Innes Wise, , , Aditi Gupta, , , David Leinkram, , , Timothy G. H. Manzie, , , Krishnan Parthasarathi, , , James Wykes, , , Catriona Froggatt, , , Gordon Wallace, , , David R. McKenzie, , , Jeremy M. Crook, , and , Jonathan R. Clark, ","doi":"10.1021/acsabm.5c01985","DOIUrl":"10.1021/acsabm.5c01985","url":null,"abstract":"<p >This protocol was developed to assess in vivo osteogenesis of 3D-printed, selectively polymerized β-tricalcium phosphate (SP-βTCP) scaffolds placed between the periosteum and native bone of sheep scapulae. The protocol spans the entire development process of scaffold design, infusion, implantation and explant analysis. 3D printed SP-βTCP scaffolds of variable pore size were infused with combinations of gelatin methacryloyl and autologous or allogeneic adipose-derived stem cells (ADSCs), and placed within plasma-treated polyetherketone bioreactor chambers manufactured by laser sintering. These were implanted for 12 weeks on the left sheep scapula and 16 weeks on the right, followed by explantation and scanning using micro computed tomography (μCT). Images were analyzed using Imalytics Preclinical software via six key steps: (i) experimental chamber selection, (ii) chamber isolation, (iii) scaffold thresholding, (iv) bone thresholding, (v) volume generation and (vi) verification. This protocol delineated the border between bone and scaffold material, allowing for reliable quantification of bone formation. ADSCs and scaffolds with a smaller pore size were associated with superior bone formation, regardless of cell origin. These results demonstrate the utility of this protocol in analyzing μCT images in situations where high-density biomaterials degrade at variable rates.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"11280–11292"},"PeriodicalIF":4.7,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601332","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}
The unprecedented use of conventional, commercial fertilizers has degraded soil health and enhanced aquatic pollution, and is inefficient in improving crop yield and productivity, suggesting the need for environmentally friendly alternatives. The current work entails the fabrication of customizable 3D-printed nanoparticle (NPs)-based micronutrient-releasing systems designed for improving plant growth parameters, nutritional aspects, and productivity. A 3D-printed precision agriculture platform was designed with various nanoparticles embedded in a gelatin matrix with engineered release profiles through a varied degree of cross-linking (0.2–1% cross-linker). The developed systems present a relatively faster release of Zn and relatively slow release of Fe and Mn nanoparticles, respectively, targeting various growth stages in wheat plants (Triticum aestivum). 3D-printed micronutrient fertilizers (MnFts) showed an improved swelling of 340%, with high water retention until 24 h, and slow, sustained release of micronutrients such as Mn, Fe, and Zn NPs for 7 days in aqueous media and 15 days in the soil medium. In this study, 3D-printed MnFts show enhancement in various growth stages of wheat plants (Triticum aestivum) (14.2% shoot length, 40.7% root length, 27.3% chlorophyll content, and 40% root volume increase), grain characteristics (∼50% more grains), total proteins (35.5% increase), pigments (32.3% increase), antioxidant enzymes (40.2% increase), and NPs content in roots, grain, and shoots. The pre- and post-treatment of the soil with 3D-printed MnFts did not affect the inherent soil microbial communities, suggesting the released Mn, Fe, and Zn NPs and degraded 3D-printed structures are nontoxic. The customizable 3D-printed structures with an engineered release profile of micronutrients targeting different growth stages of plants improve plant productivity and show no toxicity toward the soil microbial community, suggesting its potential for scalable adaptation in replacing conventional fertilizers for sustainable agriculture and environments.
{"title":"3D-Printed Precision Agriculture Platform: Integrating Nanoparticle-Based Engineered Release of Micronutrients to Enhance Growth and Productivity of Wheat Plants","authors":"Rohit Rai, , , Praveen Kumar, , , Ishan Bhattacharyya, , and , Prodyut Dhar*, ","doi":"10.1021/acsabm.5c01457","DOIUrl":"10.1021/acsabm.5c01457","url":null,"abstract":"<p >The unprecedented use of conventional, commercial fertilizers has degraded soil health and enhanced aquatic pollution, and is inefficient in improving crop yield and productivity, suggesting the need for environmentally friendly alternatives. The current work entails the fabrication of customizable 3D-printed nanoparticle (NPs)-based micronutrient-releasing systems designed for improving plant growth parameters, nutritional aspects, and productivity. A 3D-printed precision agriculture platform was designed with various nanoparticles embedded in a gelatin matrix with engineered release profiles through a varied degree of cross-linking (0.2–1% cross-linker). The developed systems present a relatively faster release of Zn and relatively slow release of Fe and Mn nanoparticles, respectively, targeting various growth stages in wheat plants (<i>Triticum aestivum</i>). 3D-printed micronutrient fertilizers (MnFts) showed an improved swelling of 340%, with high water retention until 24 h, and slow, sustained release of micronutrients such as Mn, Fe, and Zn NPs for 7 days in aqueous media and 15 days in the soil medium. In this study, 3D-printed MnFts show enhancement in various growth stages of wheat plants (<i>Triticum aestivum</i>) (14.2% shoot length, 40.7% root length, 27.3% chlorophyll content, and 40% root volume increase), grain characteristics (∼50% more grains), total proteins (35.5% increase), pigments (32.3% increase), antioxidant enzymes (40.2% increase), and NPs content in roots, grain, and shoots. The pre- and post-treatment of the soil with 3D-printed MnFts did not affect the inherent soil microbial communities, suggesting the released Mn, Fe, and Zn NPs and degraded 3D-printed structures are nontoxic. The customizable 3D-printed structures with an engineered release profile of micronutrients targeting different growth stages of plants improve plant productivity and show no toxicity toward the soil microbial community, suggesting its potential for scalable adaptation in replacing conventional fertilizers for sustainable agriculture and environments.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"10779–10792"},"PeriodicalIF":4.7,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585462","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}
Rapid and accurate detection of procalcitonin (PCT), a major biomarker for bacterial infections and sepsis, remains a pressing need in clinical diagnostics because sepsis progresses rapidly and may initially present with nonspecific or even subtle symptoms. Herein, we report a CRISPR-Cas12a-based fluorescence biosensing platform for ultrasensitive detection of PCT. The platform employs antibody-functionalized magnetic beads (MBs) for specific protein enrichment and antibody- and oligonucleotide- dual-functionalized gold nanoparticles (AuNPs) for high-density DNA payload. After sandwich complex formation with the target PCT, a programmed ssDNA strand is released by thermal denaturation, which then activates Cas12a collateral cleavage, thereby generating a fluorescence signal. Thorough physicochemical characterizations, including zeta potential, dynamic light scattering, UV–vis spectroscopy, and TEM, were carried out to confirm the successful functionalization of MBs and AuNPs. The developed PCT sensor was highly sensitive with a limit of detection (LOD) reaching 3 pg/mL. Moreover, the biosensor exhibited an excellent specificity toward PCT against clinically relevant interferents such as C-reactive protein (CRP), interleukin-2β (IL-2β), interleukin-6 (IL-6), human serum albumin (HSA), and bovine serum albumin (BSA), and simulated serum sample analysis was successfully carried out with the recoveries ranging from 108 to 122%. The PCT sensing technique developed in this work offers the potential to be expanded to construct a multiplexing platform for simultaneous detection of multiple biomarker species for early and accurate disease diagnosis.
{"title":"Enhanced CRISPR-Cas12a Fluorescent Assay for Detecting Trace Levels of Procalcitonin","authors":"Sathishkumar Munusamy, , , Rana Jahani, , , Haiyan Zheng, , , Jun Chen, , , Juanhua Kong, , , Yuan Zhao, , , Lorelei Guan, , , Shuo Zhou*, , and , Xiyun Guan*, ","doi":"10.1021/acsabm.5c01535","DOIUrl":"10.1021/acsabm.5c01535","url":null,"abstract":"<p >Rapid and accurate detection of procalcitonin (PCT), a major biomarker for bacterial infections and sepsis, remains a pressing need in clinical diagnostics because sepsis progresses rapidly and may initially present with nonspecific or even subtle symptoms. Herein, we report a CRISPR-Cas12a-based fluorescence biosensing platform for ultrasensitive detection of PCT. The platform employs antibody-functionalized magnetic beads (MBs) for specific protein enrichment and antibody- and oligonucleotide- dual-functionalized gold nanoparticles (AuNPs) for high-density DNA payload. After sandwich complex formation with the target PCT, a programmed ssDNA strand is released by thermal denaturation, which then activates Cas12a collateral cleavage, thereby generating a fluorescence signal. Thorough physicochemical characterizations, including zeta potential, dynamic light scattering, UV–vis spectroscopy, and TEM, were carried out to confirm the successful functionalization of MBs and AuNPs. The developed PCT sensor was highly sensitive with a limit of detection (LOD) reaching 3 pg/mL. Moreover, the biosensor exhibited an excellent specificity toward PCT against clinically relevant interferents such as C-reactive protein (CRP), interleukin-2β (IL-2β), interleukin-6 (IL-6), human serum albumin (HSA), and bovine serum albumin (BSA), and simulated serum sample analysis was successfully carried out with the recoveries ranging from 108 to 122%. The PCT sensing technique developed in this work offers the potential to be expanded to construct a multiplexing platform for simultaneous detection of multiple biomarker species for early and accurate disease diagnosis.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"10818–10826"},"PeriodicalIF":4.7,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145595421","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}
Zijun Li, , , Yifan Liu, , , Qiwei Wang, , , Lili Shi*, , and , Tao Li*,
Sulfur dioxide is one of the gaseous signaling molecules involved in many physiological and pathological processes of living cells, and label-free monitoring of the release of SO2 on the cell surface provides a facile way to investigate the related cellular processes. Toward this goal, here we engineer a hairpin-containing i-motif (iM-Hp) DNA that effectively binds a benzothiazole-based SO2-responsive fluorescent probe (PSMB) and remarkably promotes its fluorescence emission. When this light-up system is incubated with SO2 in aqueous solution, the addition of HSO3– to the C═C bond of PSMB destroys the fluorophore structure, accompanied by a sharp decrease in the fluorescence intensity. In this way, SO2 can be sensitively detected with a high specificity. Based on it, we further construct a cell membrane-anchored SO2 fluorescent sensor for label-free monitoring the release of SO2 from HeLa cells stimulated by lipopolysaccharide (LPS), a well-known inducer for cell inflammation. It shows that the level of SO2 exocytosis increases gradually within 4 h after incubation with LPS, whereas the cell viability almost remains unchanged during this period. This finding discloses a postdrug progressive process of inflammatory cells, highlighting the significant potential of our designed light-up system in monitoring drug-induced early cell lesion.
{"title":"Engineering Ligand-Interactive Hairpin-Containing I-Motif DNA as a Generic Light-Up System for Label-Free Cell-Membrane-Anchored Sulfur Dioxide Biosensors","authors":"Zijun Li, , , Yifan Liu, , , Qiwei Wang, , , Lili Shi*, , and , Tao Li*, ","doi":"10.1021/acsabm.5c01284","DOIUrl":"10.1021/acsabm.5c01284","url":null,"abstract":"<p >Sulfur dioxide is one of the gaseous signaling molecules involved in many physiological and pathological processes of living cells, and label-free monitoring of the release of SO<sub>2</sub> on the cell surface provides a facile way to investigate the related cellular processes. Toward this goal, here we engineer a hairpin-containing i-motif (iM-Hp) DNA that effectively binds a benzothiazole-based SO<sub>2</sub>-responsive fluorescent probe (PSMB) and remarkably promotes its fluorescence emission. When this light-up system is incubated with SO<sub>2</sub> in aqueous solution, the addition of HSO<sub>3</sub><sup>–</sup> to the C═C bond of PSMB destroys the fluorophore structure, accompanied by a sharp decrease in the fluorescence intensity. In this way, SO<sub>2</sub> can be sensitively detected with a high specificity. Based on it, we further construct a cell membrane-anchored SO<sub>2</sub> fluorescent sensor for label-free monitoring the release of SO<sub>2</sub> from HeLa cells stimulated by lipopolysaccharide (LPS), a well-known inducer for cell inflammation. It shows that the level of SO<sub>2</sub> exocytosis increases gradually within 4 h after incubation with LPS, whereas the cell viability almost remains unchanged during this period. This finding discloses a postdrug progressive process of inflammatory cells, highlighting the significant potential of our designed light-up system in monitoring drug-induced early cell lesion.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"10682–10689"},"PeriodicalIF":4.7,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145595487","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}
Ekaterina V. Kukovyakina, , , Pavel P. Kulikov, , , Dmitry V. Bagrov, , , Andrey V. Moiseenko, , , Tatiana S. Trifonova, , , Alina A. Isakova, , , Margarita L. Shuvalova, , , Elena V. Svirshchevskaya, , , Irina I. Khan, , , Vadim S. Pokrovsky, , , Marine E. Gasparian, , , Andrey N. Kuskov, , and , Anne V. Yagolovich*,
Nanosized carriers based on amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) are a versatile delivery system for various therapeutic agents such as anti-inflammatory drugs and plasmid DNA, as well as targeted antitumor drugs and proteins. Earlier, we developed Amph-PVP-based nanoparticles decorated by a modified DR5-specific TRAIL variant DR5-B (PVP-DR5-B) or containing the proteasomal inhibitor bortezomib (PVP-BTZ). Both DR5-B and BTZ have antitumor properties and, when combined, act synergistically on tumor cells. In the present study, Amph-PVP nanoparticles were loaded with BTZ and subsequently decorated with the TRAIL variant DR5-B, producing a dual polymeric bionanocomposite system PVP-BTZ-DR5-B. Using 2D and 3D in vitro cultures of human glioblastoma cell lines U87MG and T98G, it was demonstrated that PVP-BTZ-DR5-B nanoparticles were internalized and accumulated in cells more efficiently, demonstrating significantly enhanced cytotoxicity compared to free DR5-B or PVP-BTZ nanoparticles loaded with bortezomib alone. PVP-BTZ-DR5-B nanoparticles also penetrated the blood–brain barrier more efficiently than DR5-B in an in vitro model. Finally, the enhanced antitumor effect of PVP-BTZ-DR5-B was demonstrated in a xenograft model of U87MG glioblastoma cells in zebrafish embryos in vivo. Thereby, coloading of BTZ and DR5-B into the Amph-PVP nanoparticles is a promising approach to enhance the antitumor efficacy of free drugs and overcome glioblastoma resistance.
{"title":"Codelivery of Bortezomib and Modified DR5-Selective TRAIL via Amphiphilic Poly(N-vinylpyrrolidone) Bionanocomposites to Overcome Glioblastoma Resistance","authors":"Ekaterina V. Kukovyakina, , , Pavel P. Kulikov, , , Dmitry V. Bagrov, , , Andrey V. Moiseenko, , , Tatiana S. Trifonova, , , Alina A. Isakova, , , Margarita L. Shuvalova, , , Elena V. Svirshchevskaya, , , Irina I. Khan, , , Vadim S. Pokrovsky, , , Marine E. Gasparian, , , Andrey N. Kuskov, , and , Anne V. Yagolovich*, ","doi":"10.1021/acsabm.5c01651","DOIUrl":"10.1021/acsabm.5c01651","url":null,"abstract":"<p >Nanosized carriers based on amphiphilic poly(<i>N</i>-vinylpyrrolidone) (Amph-PVP) are a versatile delivery system for various therapeutic agents such as anti-inflammatory drugs and plasmid DNA, as well as targeted antitumor drugs and proteins. Earlier, we developed Amph-PVP-based nanoparticles decorated by a modified DR5-specific TRAIL variant DR5-B (PVP-DR5-B) or containing the proteasomal inhibitor bortezomib (PVP-BTZ). Both DR5-B and BTZ have antitumor properties and, when combined, act synergistically on tumor cells. In the present study, Amph-PVP nanoparticles were loaded with BTZ and subsequently decorated with the TRAIL variant DR5-B, producing a dual polymeric bionanocomposite system PVP-BTZ-DR5-B. Using 2D and 3D <i>in vitro</i> cultures of human glioblastoma cell lines U87MG and T98G, it was demonstrated that PVP-BTZ-DR5-B nanoparticles were internalized and accumulated in cells more efficiently, demonstrating significantly enhanced cytotoxicity compared to free DR5-B or PVP-BTZ nanoparticles loaded with bortezomib alone. PVP-BTZ-DR5-B nanoparticles also penetrated the blood–brain barrier more efficiently than DR5-B in an <i>in vitro</i> model. Finally, the enhanced antitumor effect of PVP-BTZ-DR5-B was demonstrated in a xenograft model of U87MG glioblastoma cells in zebrafish embryos <i>in vivo</i>. Thereby, coloading of BTZ and DR5-B into the Amph-PVP nanoparticles is a promising approach to enhance the antitumor efficacy of free drugs and overcome glioblastoma resistance.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"10965–10978"},"PeriodicalIF":4.7,"publicationDate":"2025-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585451","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}
Vanessa M. E. da Rocha, , , Ana Paula B. Wille, , , Ana Paula S. e Silva, , , Matheus S. Gularte, , , Mauro P. Soares, , , Marcelle M. Silveira, , , Janice Giongo, , , Rodrigo A. Vaucher, , , Jeff R. Spitzner, , , André R. Fajardo, , , Enrique Javier Carvajal Barriga*, , and , Ethel A. Wilhelm*,
Atopic dermatitis (AD) and diabetic wounds are chronic inflammatory skin conditions with limited treatment options. This study investigates the therapeutic potential of sprayable colloidal suspensions composed of cellulose and mannan nanocrystals (CNC/MN) derived from ivory nuts in preclinical models of AD and diabetic wound healing. AD was induced in BALB/c mice using 2,4-dinitrochlorobenzene (DNCB), while diabetes was induced in Swiss mice via streptozotocin before dorsal wounds were created. AD severity was assessed through clinical scoring, scratching behavior, histopathology, oxidative stress markers, inflammatory profiling, and emotional domain evaluation. Wound closure rates, bacterial burden, and histological analysis were used to evaluate diabetic wound healing. CNC/MN-based suspensions alleviated DNCB-induced inflammatory skin damage (back: around 48%, and dorsal skin: around 78%) and reversed depressive-like behavior (around 50%) without affecting locomotor activity. The formulation with higher MN content showed superior efficacy in reducing erythema, edema, and neutrophilic infiltration while restoring antioxidant enzyme activity. In diabetic wounds, suspensions with lower MN or without MN content exhibited the best results, enhancing wound closure, collagen deposition, and reducing inflammation. The CNC/MN-based suspension with lower MN content significantly reduced bacterial colonization in the wound site (around 23%). These findings demonstrate that CNC/MN colloidal suspensions are promising sprayable biomaterials for treating inflammatory skin disorders, mitigating cutaneous and neuropsychiatric AD symptoms while promoting tissue regeneration in diabetic wounds. This study highlights their dual therapeutic potential and sustainable origin, offering an innovative treatment alternative for chronic skin disease.
{"title":"Sprayable Cellulose and Mannan Nanocrystals from Ivory Nuts for Treatment of Skin Diseases in Mice","authors":"Vanessa M. E. da Rocha, , , Ana Paula B. Wille, , , Ana Paula S. e Silva, , , Matheus S. Gularte, , , Mauro P. Soares, , , Marcelle M. Silveira, , , Janice Giongo, , , Rodrigo A. Vaucher, , , Jeff R. Spitzner, , , André R. Fajardo, , , Enrique Javier Carvajal Barriga*, , and , Ethel A. Wilhelm*, ","doi":"10.1021/acsabm.5c01708","DOIUrl":"10.1021/acsabm.5c01708","url":null,"abstract":"<p >Atopic dermatitis (AD) and diabetic wounds are chronic inflammatory skin conditions with limited treatment options. This study investigates the therapeutic potential of sprayable colloidal suspensions composed of cellulose and mannan nanocrystals (CNC/MN) derived from ivory nuts in preclinical models of AD and diabetic wound healing. AD was induced in BALB/c mice using 2,4-dinitrochlorobenzene (DNCB), while diabetes was induced in Swiss mice via streptozotocin before dorsal wounds were created. AD severity was assessed through clinical scoring, scratching behavior, histopathology, oxidative stress markers, inflammatory profiling, and emotional domain evaluation. Wound closure rates, bacterial burden, and histological analysis were used to evaluate diabetic wound healing. CNC/MN-based suspensions alleviated DNCB-induced inflammatory skin damage (back: around 48%, and dorsal skin: around 78%) and reversed depressive-like behavior (around 50%) without affecting locomotor activity. The formulation with higher MN content showed superior efficacy in reducing erythema, edema, and neutrophilic infiltration while restoring antioxidant enzyme activity. In diabetic wounds, suspensions with lower MN or without MN content exhibited the best results, enhancing wound closure, collagen deposition, and reducing inflammation. The CNC/MN-based suspension with lower MN content significantly reduced bacterial colonization in the wound site (around 23%). These findings demonstrate that CNC/MN colloidal suspensions are promising sprayable biomaterials for treating inflammatory skin disorders, mitigating cutaneous and neuropsychiatric AD symptoms while promoting tissue regeneration in diabetic wounds. This study highlights their dual therapeutic potential and sustainable origin, offering an innovative treatment alternative for chronic skin disease.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"11019–11035"},"PeriodicalIF":4.7,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsabm.5c01708","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Small-diameter vascular grafts (SDVGs) have great potential in the treatment of cardiovascular diseases. However, thrombosis and restenosis of SDVGs, caused by incomplete endothelium and abnormal smooth muscle cell proliferation, limit their clinical applications. Hydrogen sulfide (H2S) is a crucial signaling molecule in the cardiovascular system, playing a vital role in physiological processes such as blood pressure regulation, angiogenesis, and the reduction of vascular hyperplasia, as well as exerting anti-inflammatory effects. In this study, a human hair keratin-based H2S donor was synthesized and coelectrospun with poly(ε-caprolactone) to develop an H2S-releasing vascular graft. The graft effectively promoted the growth and migration of HUVECs and suppressed the proliferation of HUASMCs by releasing H2S. Interestingly, the grafts accelerated endothelium formation under shear stress and protected them from oxidative stress. In vivo experiment also demonstrated that the endothelial layer regenerated without detectable thickening of the smooth muscle layer after 1 month of implantation, which was attributed to the H2S-mediated effect. Taken together, this study provided strategies for the tissue remolding of small-diameter vascular grafts.
{"title":"Endothelium-Protective, Intimal Hyperplasia-Resistant PCL/KAT Scaffold for Vascular Implants","authors":"Dawei Jin, , , Pengfei Li, , , Yu Sun, , , Yanjun Pan, , , Jiang Yuan*, , and , Meng Yin*, ","doi":"10.1021/acsabm.5c01768","DOIUrl":"10.1021/acsabm.5c01768","url":null,"abstract":"<p >Small-diameter vascular grafts (SDVGs) have great potential in the treatment of cardiovascular diseases. However, thrombosis and restenosis of SDVGs, caused by incomplete endothelium and abnormal smooth muscle cell proliferation, limit their clinical applications. Hydrogen sulfide (H<sub>2</sub>S) is a crucial signaling molecule in the cardiovascular system, playing a vital role in physiological processes such as blood pressure regulation, angiogenesis, and the reduction of vascular hyperplasia, as well as exerting anti-inflammatory effects. In this study, a human hair keratin-based H<sub>2</sub>S donor was synthesized and coelectrospun with poly(ε-caprolactone) to develop an H<sub>2</sub>S-releasing vascular graft. The graft effectively promoted the growth and migration of HUVECs and suppressed the proliferation of HUASMCs by releasing H<sub>2</sub>S. Interestingly, the grafts accelerated endothelium formation under shear stress and protected them from oxidative stress. In vivo experiment also demonstrated that the endothelial layer regenerated without detectable thickening of the smooth muscle layer after 1 month of implantation, which was attributed to the H<sub>2</sub>S-mediated effect. Taken together, this study provided strategies for the tissue remolding of small-diameter vascular grafts.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"11145–11154"},"PeriodicalIF":4.7,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561977","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}
Ming Li, , , Wanying Zhao, , , Luyao Bai, , , Shanshan Yuan, , , Yuting Zhu*, , , Han Wang*, , and , Junjie Deng*,
The long-term survival of allografts is primarily compromised by immune rejection, in which M1 macrophage-mediated tissue damage and effector T cell infiltration have been identified as major contributors. Current clinical immunosuppressive drugs face critical limitations, as they either fail to coordinately regulate these two immune cell populations or induce systemic infections and metabolic disorders. To address this challenge, we developed an aminooxyacetic acid (AOAA)-loaded hydrogel delivery system (AOAA-Gel) based on covalently cross-linked oxidized sodium alginate/carboxymethyl chitosan (OSA/CMCS). This hydrogel enables localized and sustained AOAA release, while avoiding systemic toxicity. Mechanistically, AOAA-Gel coordinately modulates the M1/M2 macrophage ratio while expanding regulatory T cells at the graft site, resulting in effective suppression of both effector T cell infiltration and chronic rejection. In a murine allogeneic skin transplantation model, AOAA-Gel establishes an immunosuppressive microenvironment, significantly prolonging graft survival. These findings demonstrate a potentially safer therapeutic strategy for maintaining sustained allograft function through localized immunomodulation.
{"title":"Modulating Anti-Inflammatory Macrophage Polarization and Regulatory T Cell Differentiation via Aminooxyacetic Acid-Loaded Hydrogel for Promoting Allogeneic Skin Transplantation","authors":"Ming Li, , , Wanying Zhao, , , Luyao Bai, , , Shanshan Yuan, , , Yuting Zhu*, , , Han Wang*, , and , Junjie Deng*, ","doi":"10.1021/acsabm.5c01654","DOIUrl":"10.1021/acsabm.5c01654","url":null,"abstract":"<p >The long-term survival of allografts is primarily compromised by immune rejection, in which M1 macrophage-mediated tissue damage and effector T cell infiltration have been identified as major contributors. Current clinical immunosuppressive drugs face critical limitations, as they either fail to coordinately regulate these two immune cell populations or induce systemic infections and metabolic disorders. To address this challenge, we developed an aminooxyacetic acid (AOAA)-loaded hydrogel delivery system (AOAA-Gel) based on covalently cross-linked oxidized sodium alginate/carboxymethyl chitosan (OSA/CMCS). This hydrogel enables localized and sustained AOAA release, while avoiding systemic toxicity. Mechanistically, AOAA-Gel coordinately modulates the M1/M2 macrophage ratio while expanding regulatory T cells at the graft site, resulting in effective suppression of both effector T cell infiltration and chronic rejection. In a murine allogeneic skin transplantation model, AOAA-Gel establishes an immunosuppressive microenvironment, significantly prolonging graft survival. These findings demonstrate a potentially safer therapeutic strategy for maintaining sustained allograft function through localized immunomodulation.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 12","pages":"10979–10989"},"PeriodicalIF":4.7,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561912","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}