ACS Applied Bio Materials最新文献

{"title":"Engineering a Photoactive Live Bacterial Hybrid: MXene/MoS2@M.bvs for Oxygenation-Boosted Cancer Immunotherapy","authors":"Ammavasi Chandran Ambigaibalan,&nbsp;Sivaraj Mehnath,&nbsp;Kannaiyakumar Dharshini,&nbsp;Arivalagan Ponbharathi,&nbsp;Chithaiyan Kamaladevi Sowndharya,&nbsp;Murugaraj Jeyaraj","doi":"10.1021/acsabm.6c01194","DOIUrl":"10.1021/acsabm.6c01194","url":null,"abstract":"<p>Hypoxic conditions in the tumor microenvironment, which escape immune surveillance, are a major hindrance to controlling the antitumor effect of nanomaterials. In this work, MXene/MoS₂ @<em>M.bvs</em> photoactive live bacteria were developed. NIR irradiation elevates the oxygen level, induces the photothermal effect, interferes with the Ado A2A receptor (Adenosine A2AR) metabolic pathway, and triggers cancer immunotherapy. An acid-etched MXene sheet was fabricated from the MAX phase; exfoliated MoS₂ was composited with a thin MXene sheet to form self-assembled MXene/MoS₂. Nanocomposites were conjugated to <em>Mycobacterium bovis</em> (<em>M.bvs</em>) through a carbodiimide reaction, and they formed a stable rod shape, as confirmed through HRTEM analysis. The in vitro catalytic effect of MXene/MoS₂@<em>M.bvs</em> toward H₂O₂ was evaluated, and a reduction of the Ado level was observed by downregulation of A2AR expression. Nanocomposites not only improved the photothermal effect but also were directly involved in the immune stimulation. The level of cytokine production and cytotoxic T-cell activation was higher for MXene/MoS₂@<em>M.bvs</em> compared to the MXene/MoS₂. In vivo studies showed that MXene/MoS₂@<em>M.bvs</em> + NIR exhibited higher antitumor activity, longer survival time, biosafety, and inhibition of tumor growth. It also promotes DC maturation, increases TNF-α and IL-6, and induces a potent antitumor immune response. Overall, the photoactive live bacterial nanocomposites effectively enhance the synergistic effect of photothermal cancer immunotherapy.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 19","pages":"9158–9172"},"PeriodicalIF":5.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149014882","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":"Silk Acid-Mediated Phase Separation of PEDOT:PSS for Biocompatible, Flexible Neural Interfaces","authors":"Kun Liang,&nbsp;Tian Xia,&nbsp;Fan Zhang,&nbsp;Ran Jin,&nbsp;Shuhui Ren,&nbsp;Lixiang Xing,&nbsp;Saisai Wang,&nbsp;Shurong Dong,&nbsp;Shaomin Zhang,&nbsp;Chengchen Guo,&nbsp;Bowen Zhu","doi":"10.1021/acsabm.6c01162","DOIUrl":"10.1021/acsabm.6c01162","url":null,"abstract":"<p>Flexible multielectrode arrays (MEAs) are pivotal for elucidating the complex mechanisms of neural information transfer. A key challenge lies in developing ultrathin, highly compliant electrodes with high conductivity, low impedance, and excellent biocompatibility to establish conformal contact with organ surfaces. This enables precise recording of electrophysiological signal propagation with high spatiotemporal resolution, critical for deciphering physiological function. Conventional organic substrates, often thicker and possessing a higher Young’s modulus, typically lack the necessary stretchability and conformability for dynamic interfaces. To overcome this, gold electrodes were modified by spin-coating a composite conductive layer of poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) doped with silk acid (SA) onto an ultrathin parylene substrate. Impedance of these flexible MEAs decreased with SA doping, indicating enhanced electrical conductivity. Furthermore, SA incorporation mitigated the intrinsic cytotoxicity of PEDOT:PSS. This optimized electrode design enables epileptic signal recording with a high signal-to-noise ratio (SNR) in the rat somatosensory cortex.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 19","pages":"9135–9143"},"PeriodicalIF":5.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035584","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":"Interfacial Engineering with Amphiphilic Cationic Polymers: Role of Alkyl Chain Length in Biofilm Suppression and Corrosion Protection","authors":"Harshal Mehta,&nbsp;Archana V.,&nbsp;Preeti Srivastava,&nbsp;Leena Nebhani","doi":"10.1021/acsabm.6c01485","DOIUrl":"10.1021/acsabm.6c01485","url":null,"abstract":"<p>Biofilm formation promotes microbiologically influenced corrosion (MIC) in marine environments, demanding coatings that can resist bacterial adhesion and corrosion simultaneously. Herein, we report amphiphilic cationic polymer coatings based on quaternized poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) with varying alkyl chain lengths (C₄–C₁₂) deposited over an inherently antimicrobial tannic acid–Cu (TA–Cu) interfacial layer on stainless steel. Increasing the alkyl chain length gives rise to noticeable surfactant-like action, resulting in improved hydrophobicity and reduced surface free energy of the coatings. Specifically, the dodecyl-functionalized polymer has the lowest surface free energy which effectively reduces bacterial adhesion and inhibits the formation of biofilm of <em>Pseudomonas aeruginosa</em>. The electrochemical tests show a significant drop in corrosion current density and rise in impedance with increasing chain length. The PC₁₂ coating exhibits diffusion-limited corrosion behavior, which indicates a dense and impermeable barrier. In contrast, shorter chain counterparts provide only limited protection as these have less affinity to create a dense coating. The long-chain quaternized PDMAEMA coatings proved efficient multifunctional surfaces to reduce MIC in marine environments owing to their combined effects of decreased surface free energy, improved hydrophobicity, and cationic nature.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 19","pages":"9222–9233"},"PeriodicalIF":5.6,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035607","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":"Enhancing Tumor Immunogenicity through Hyaluronic Acid-Mediated Delivery of Nonself Antigenic Peptides.","authors":"Aki Kakinami, Sayaka Oitate, Shinichi Mochizuki","doi":"10.1021/acsabm.6c01600","DOIUrl":"https://doi.org/10.1021/acsabm.6c01600","url":null,"abstract":"<p><p>Tumor-specific cytotoxic T cells (CTLs) recognize and eliminate tumor cells presenting the tumor-associated antigens on major histocompatibility complex (MHC) class I molecules. However, the efficacy of vaccine-induced CTLs is often limited by the low immunogenicity of self-derived tumor antigens. Because the magnitude of an immune response is closely associated with antigen immunogenicity, strategies that enhance the antigenicity of tumor cells can improve the effectiveness of cancer vaccines. In this study, we prepared a series of conjugates consisting of hyaluronic acid (HA), a tumor-targeting carrier, and the highly immunogenic ovalbumin (OVA)-derived peptide OVA257-264. The peptide was conjugated to amino-modified HA through a disulfide linkage using a cysteine-extended OVA257-264 (C-OVA257-264). We then evaluated whether delivery of C-OVA257-264 could induce presentation of a foreign antigen on MHC class I molecules of B16F10 melanoma cells. Treatment of B16F10 cells with the conjugate HA-C-OVA257-264 efficiently induced presentation of C-OVA257-264 on H-2Kb molecules. Coculture of B16F10 cells treated with HA-C-OVA257-264 and splenocytes containing OVA257-264-specific CTLs resulted in robust interferon gamma production and pronounced CTL-mediated cytotoxicity. Similar antigen results were obtained using C-SARS902-909, a peptide capable of binding H-2Kb and potentially compatible with selected human HLA class I molecules. These findings indicate that foreign antigenic peptides delivered by HA can be presented on MHC class I molecules of tumor cells and subsequently recognized by antigen-specific CTLs. This antigen-replacement strategy represents a promising platform for the development of next-generation cancer vaccines and other antigen-specific immunotherapies.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100979","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":"Stress, Insomnia, and Leisure in Dementia Family Caregivers. Correlates with Distress during the COVID-19 Pandemic.","authors":"Lucía Jiménez-Gonzalo, Carlos Vara-García, Rosa Romero-Moreno, María Márquez-González, Samara Barrera-Caballero, Javier Olazarán, Andrés Losada-Baltar","doi":"10.1080/07317115.2022.2102955","DOIUrl":"10.1080/07317115.2022.2102955","url":null,"abstract":"<p><p>The COVID-19 pandemic added a new stress source for caregivers. Many aspects influence the potential depressive or anxiety symptomatology in caregivers. This study explored the association among COVID-19 related stressors, insomnia, leisure, and caregivers' depression and anxiety. 101 family caregivers of people with dementia were asked about COVID-19 related stressors, insomnia, leisure, depression and anxiety symptoms. Four regression models with caregivers' depression and anxiety symptoms as dependent variables were tested. Four potential mediation models were investigated. Two of them had insomnia as the independent variable and leisure as a mediator, and the other two had leisure as the independent variable and insomnia as a mediator. Regression models accounted for 48% and 40.6% of the variance in depressive and anxiety symptoms, respectively. The four mediator models were statistically significant. Findings suggest two potential mechanisms affecting caregivers' distress during the pandemic. Insomnia and leisure significantly contributed to explain caregivers' anxiety and depressive symptoms, even after controlling for COVID-19 related stressors. Provision of resources to increase the chances of caregivers engaging in leisure activities, alongside a reduction of barriers potentially limiting good sleep, may contribute significantly to improving the depression and anxiety symptoms of family caregivers.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1204-1215"},"PeriodicalIF":5.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40634998","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":"Engineering the Structural Organization of Tryptophan in Crystalline Materials for Tunable Functionality.","authors":"Oliver Ton, Sidhanth Duvvuri, Carol Korzeniewski, Raheleh Ravanfar","doi":"10.1021/acsabm.6c01612","DOIUrl":"https://doi.org/10.1021/acsabm.6c01612","url":null,"abstract":"<p><p>Tryptophan is a biologically important redox-active amino acid whose functions in proteins, including long-range electron transfer, protection against oxidative damage, and environmental sensing, are governed not only by its chemical identity but also by its precise structural organization. Inspired by this biological principle, we investigated whether controlling the organization of tryptophan within crystalline materials could provide a strategy for modulating its physicochemical properties and molecular accessibility. Using identical molecular components but distinct assembly pathways, tryptophan was organized either as a confined guest within a preformed Zn-imidazolate framework, yielding a star-shaped crystalline architecture, or as an integral coordination component during framework growth, producing a distinct layered Zn-tryptophan crystalline framework. Although assembled from the same building blocks, these two organization modes generated fundamentally different crystal structures, morphologies, and mechanisms of biomolecule incorporation. In both architectures, incorporation of tryptophan into the crystalline environment preserved its intrinsic fluorescence while producing robust fluorescence under multiple excitation wavelengths, highlighting the strong influence of molecular organization on its optical response. The structural modes also exhibited distinct encapsulation efficiencies and pH-dependent molecular accessibility, while secondary Ca2+-crosslinked alginate fixation provided an additional level of control over guest retention without disrupting the underlying crystalline architecture. These results demonstrate that engineering the structural organization of tryptophan provides a versatile strategy for tuning the optical behavior, molecular accessibility, and functional integration of a biologically important redox-active amino acid in crystalline materials, establishing a foundation for future biomimetic redox architectures, responsive sensing platforms, and controlled molecular delivery.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149056624","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":"Nanostructured Silver-Coated Silicone Tracheal Stents Confer Hybrid Anti-Biofilm Activity In Vivo","authors":"Cristina Garcia-Bonillo,&nbsp;Rosa López-Lisbona,&nbsp;Marta Díez-Ferrer,&nbsp;Sara Marti,&nbsp;Joan Gilabert,&nbsp;Noelia Cubero,&nbsp;Salud Santos,&nbsp;Salvador Borrós,&nbsp;Antoni Rosell,&nbsp;Robert Texidó","doi":"10.1021/acsabm.6c00591","DOIUrl":"10.1021/acsabm.6c00591","url":null,"abstract":"<p>Bacterial colonization and biofilm formation remain major limitations of airway stenting, contributing to device obstruction and infection-related complications. Here, we translated to silicone tracheal stents a previously developed plasma-assisted micro/nanostructured silver interface designed to provide hybrid anti-biofilm activity through reduced bacterial adhesion and controlled silver release. The coated stents were characterized to confirm the generation of the nanostructured silver coating and were evaluated against Gram-positive and Gram-negative bacteria in vitro, followed by in vivo assessment in a miniature pig airway model. In vitro, the coating reproduced the dual bacteriophobic and silver-mediated antimicrobial behavior previously observed on model silicone surfaces. In vivo, animals implanted with silver-coated stents showed lower endpoint bacterial loads in bronchial washes than those receiving commercial stents (1.0 × 10⁸ vs 1.2 × 10⁹ CFU/mL, <em>p</em> =0.0085). Bacterial adhesion on explanted stents was also markedly lower for coated devices (10⁹ vs 10¹¹ CFU /cm², 99.8% reduction, <em>p</em> &lt; 0.0001), and scanning electron microscopy showed a thinner and less mature biofilm structure. Potentially pathogenic bacteria, including <em>Klebsiella pneumoniae</em> and <em>Pseudomonas aeruginosa</em>, were more frequently detected on commercial stents, whereas coated stents were mainly associated with the native respiratory microbiota. Overall, these results indicate that nanostructured silver-coated silicone tracheal stents display hybrid anti-biofilm functionality in a challenging in vivo airway setting.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 18","pages":"8456–8470"},"PeriodicalIF":5.6,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885638","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":"A Pluronic F127/Carbopol 974P Nanogel Provides a Water-Dispersible Formulation of Duguetia stelechantha Essential Oil for Developmental Safety Assessment in Zebrafish Embryos","authors":"Raiene Lisboa Rocha,&nbsp;Lorranny Pereira de Assis Valadares,&nbsp;Camila Silva da Costa,&nbsp;Melissa Pires Souza,&nbsp;Erick Rafael Dias Rates,&nbsp;Marcos Bispo Pinheiro Camara,&nbsp;Emmanoel Vilaça Costa,&nbsp;Luciana Magalhães Rebelo Alencar,&nbsp;Thiago Lopes Rocha,&nbsp;Renato Sonchini Gonçalves","doi":"10.1021/acsabm.6c01381","DOIUrl":"10.1021/acsabm.6c01381","url":null,"abstract":"<p>Polymeric nanogels are attractive biomaterial platforms for preparing aqueous dispersions of hydrophobic bioactive compounds, including essential oils. However, incorporating chemically complex, terpene-rich oils into these polymeric systems may modify their supramolecular organization, colloidal behavior, and biological responses. Such physicochemical changes do not, by themselves, demonstrate controlled release or quantitative delivery performance. Here, we developed and characterized a Pluronic F127/Carbopol 974P nanogel incorporating a nominal concentration of 1% (w/w) <em>Duguetia stelechantha</em> essential oil droplets (EODs) and evaluated the developmental safety profile of the complete formulation using zebrafish (<em>Danio rerio</em>) embryos as a vertebrate screening model. Chemical analysis showed that EODs were dominated by sabinene (41.44%), terpinen-4-ol (17.61%), and spathulenol (9.21%). The optimized EOD-incorporated nanogel (nGDs) provided a homogeneous aqueous dispersion of the hydrophobic oil, whereas FTIR, DSC, DLS, SEM, and AFM revealed formulation-dependent differences in spectral behavior, thermal transitions, hydrodynamic parameters, dried-sample morphology, and apparent nanomechanical properties. These differences are compatible with non-covalent association and changes in polymer organization but do not establish molecular localization or a specific self-assembly mechanism. The nominal oil content should not be interpreted as an experimentally determined encapsulation efficiency or analytical loading capacity. Exposure to nGDs at 50–200 μg mL^–1 induced concentration-dependent developmental toxicity, including increased mortality, altered hatching, reduced spontaneous tail coiling, cardiac impairment, and morphological abnormalities. In contrast, the oil-free polymeric matrix did not reproduce the toxicity profile observed for nGDs, indicating that the carrier alone did not account for the adverse responses induced by the complete formulation. These findings characterize the developmental safety profile of nGDs as a water-dispersible formulation designed for biological application without the addition of an organic cosolvent or another external dispersing vehicle. Without a free-EOD comparator, the results cannot determine whether formulation modified the intrinsic toxicity of the oil.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 18","pages":"8860–8877"},"PeriodicalIF":5.6,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885649","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":"Conjugation of Biomolecules to PEG as a Strategy for Efficient Protein Aggregation Inhibition","authors":"Nidhi Anilkumar Jamuna,&nbsp;Merlin Thomas,&nbsp;Dharini Arumugam,&nbsp;Sarthak Mandal","doi":"10.1021/acsabm.6c00990","DOIUrl":"10.1021/acsabm.6c00990","url":null,"abstract":"<p>Neurodegenerative diseases are a group of progressive disorders characterized by the degeneration of neurons with significant cognitive decline and motor and autonomic dysfunction. They are linked to protein aggregation that leads to cellular toxicity, neuronal death, and brain atrophy due to the accumulation of amyloid plaques and tau tangles in the brain. Recent advances in biomaterials have introduced several biocompatible polymers and conjugated biomolecules as potential inhibitors for protein aggregation. Conjugation to biocompatible polyethylene glycol (PEG) is the most widely used strategy for enhancing bioavailability, biocompatibility, and pharmacokinetic properties of small molecular drugs. In this work, we have designed and synthesized two biomolecule-polymer conjugates, namely, Tre-CA-mPEG and LA-CA-mPEG, by combining a biocompatible, nontoxic polymer monomethoxy PEG (mPEG), a steroid bile acid, cholic acid (CA), and a functional biomolecule, trehalose (Tre) or lipoic acid (LA). These building blocks have significant protein stabilization and neuroprotective attributes, which are important for protein aggregation inhibition. The size distributions of the self-assemblies formed by the Tre-CA-mPEG and LA-CA-mPEG bioconjugates were determined by dynamic light scattering (DLS) measurements. Both the PEGylated bioconjugate assemblies show promising results for inhibition of protein aggregation. The hydrophobic interactions provided predominantly by the steroidal core moiety, together with hydrogen bonding interactions within the PEG corona of the self-assemblies, play a crucial role in protein stabilization and fibrillation inhibition. LA-CA-mPEG bioconjugate exhibits superior effects in delaying aggregation kinetics and enhancing the inhibition of protein aggregation compared to the Tre-CA-mPEG bioconjugate. This enhanced protein fibrillation inhibition can be attributed to the larger hydrophobic surface and stronger interactions arising from the LA-CA-mPEG nanoassemblies.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 18","pages":"8607–8626"},"PeriodicalIF":5.6,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885661","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":"Ca-BPDC Immobilization Redistributes Regional Proteolytic Preference of Serine Proteases","authors":"Qiaobin Li,&nbsp;Md Zahidul Hasan,&nbsp;Tyeaba Tasnim Dipti,&nbsp;Helen Qin,&nbsp;Jenna Skidmore,&nbsp;Ang Guo,&nbsp;Gary A. Baker,&nbsp;Liu Liu,&nbsp;Li Feng,&nbsp;Zhongyu Yang","doi":"10.1021/acsabm.6c00770","DOIUrl":"10.1021/acsabm.6c00770","url":null,"abstract":"<p>Proteases cleave peptide bonds and generate shorter polypeptide products, finding broad applications. For applications in peptide sequencing, protein mapping, and production of bioactive polypeptides, control over where proteolysis initiates and how it proceeds is critical. Natural proteolytic selectivity primarily originates from local recognition of short amino-acid motifs. However, higher-order or regional selectivity (i.e., cleavage biased toward specific termini or domains) remains difficult even with sophisticated protein engineering or complex multi-enzyme, cascade proteolytic design. We recently reported that trypsin@Ca-BPDC preferentially cleaved the N-terminus of T4 phage lysozyme (T4L) [<em>ACS Appl. Mater. Interfaces</em> <strong>2023</strong>, 15 (7), 8927–8936], indicating a promising alternative to introduce directional or regional proteolysis through enzyme immobilization via a unique MOF, Ca-BPDC. To confirm such preference, as a follow-up of that work, here, we extend the MOF-based immobilization to two commercial serine proteases (mixture products with unreported compositions). Our time-resolved electron paramagnetic resonance (EPR) shows that, despite differing or weakly defined selectivity in solution, both commercial proteases exhibit a consistent shift toward N-terminal cleavage of T4L upon immobilized in Ca-BPDC through co-crystallization. Control experiments indicate negligible adsorption of the substrate to the Ca-BPDC alone, suggesting that directional selectivity arises from the coupled MOF–protease environment rather than substrate–MOF interactions. These results indicate that Ca-BPDC may be able to impose an additional, material-derived layer of proteolytic selection on commercial serine proteases. Thus, it may offer a practical way for directional or programmable proteolysis without enzyme chemical or genetic modification. Our immobilization platform also offers a reusable matrix compatible with real-time mechanistic analysis. This approach opens opportunities for controlled peptide generation, proteolytic selectivity tuning, and design of programmable proteolytic bioreactors.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"9 18","pages":"8507–8517"},"PeriodicalIF":5.6,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885664","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}