ACS Applied Bio Materials最新文献

{"title":"Multifunctional Near Infrared Polymer Dots for Enhanced Synergistic Photodynamic/Photothermal Effect In Vitro.","authors":"Yingfen Wu, Diane C Darland, Colin K Combs, Julia Xiaojun Zhao","doi":"10.1021/acsabm.4c01593","DOIUrl":"10.1021/acsabm.4c01593","url":null,"abstract":"<p><p>Synergistic photodynamic/photothermal therapy (PDT/PTT) can be used to target cancer cells by locally generating singlet oxygen species or increasing temperature under laser irradiation. This approach offers higher tumor ablation efficiency, lower therapeutic dose requirements, and reduced side effects compared to single treatment approaches. However, the therapeutic efficiency of PDT/PTT is still limited by the low oxygen levels within the solid tumors caused by abnormal vasculature and altered cancer cell metabolism. To address these challenges, we developed multifunctional nanoparticles with high catalytic activity for converting tumor hydrogen peroxide (H₂O₂) into oxygen (O₂). Using poly(styrene-<i>co</i>-maleic anhydride) (PSMA) as a cross-linker, we generated compact, highly fluorescent Pdots, used poly[2,6-(4,4-bis(2-ethylhexyl)-4<i>H</i>-cyclopenta[2,1-<i>b</i>;3,4-<i>b</i>']dithiophene)-<i>alt</i>-4,7-(2,1,3-benzothiadiazole)] (PCPDTBT) as a near-infrared photosensitizer for both photodynamic and photothermal applications, and incorporated manganese (Mn) ions to catalyze the H₂O₂-to-O₂ conversion. These Mn-doped Pdots significantly enhance O₂ production, achieving an enhanced ¹O₂ quantum yield from 0.46 to 0.64 with the addition of H₂O₂, achieving the goal of improving PDT efficiency. With this rational design, we produced Pdots with enhanced H₂O₂-to-¹O₂ converting ability for potential use in PDT. For photothermal applications, our Pdots generate a photothermal conversion efficiency of 53%. <i>In vitro</i> studies using human MCF7 adenocarcinoma cells confirmed the biocompatibility of these Pdots in the absence of laser exposure with a pronounced cell killing effect under laser irradiation for synergistic PDT/PTT. These results highlight the promise of Pdots in overcoming oxygen limitations, balancing the performance of PDT/PTT, and enhancing the therapeutic efficacy of PDT/PTT in cancer cells <i>in vitro</i>.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1278-1291"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995995","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":"Construction of Nonenzymatic Flexible Electrochemical Sensor for Glucose Using Bimetallic Copper Ferrite/Sulfur-Doped Graphene Oxide Water-Based Conductive Ink by Noninvasive Method.","authors":"Selen Uruc, Ozge Gorduk, Yucel Sahin","doi":"10.1021/acsabm.4c01674","DOIUrl":"10.1021/acsabm.4c01674","url":null,"abstract":"<p><p>Diabetes is a chronic disease that results in elevated blood glucose levels due to insufficient insulin production by the pancreas or impaired insulin utilization by the body. The development of effective tools for the <i>in vitro</i> detection of blood glucose is of paramount importance. Flexible electrodes serve as indispensable components in point-of-care systems, thus increasing accessibility and personalization in health monitoring. We present the preparation of handmade screen-printed electrode with water-based conductive ink for <i>in vitro</i> nonenzymatic glucose (Glu) determination at physiological pH values. The investigation aimed to identify the optimal conditions for formulating and composing the conductive ink used to create a copper ferrite/sulfur-doped graphene oxide/graphite/screen-printed electrode (CuFe₂O₄/S-GO/G/SPE). The resulting CuFe₂O₄/S-GO/G/SPE shows excellent glucose sensing ability with a limit of detection (LOD) of 2.93 μM. The superior determination at physiological pH is attributed to the complex structure formed by CuFe₂O₄ nanoparticles with glucose molecules in the basic pH conductive ink structure. Additionally, the excellent delocalization and conductivity of the S-GO particles in this complex structure contribute to improved performance. The study on artificial sweat samples resulted in achieving recovery values of 96.60% to 104.97%. In conclusion, the nonenzymatic and noninvasive Glu sensor printed with conductive ink containing CuFe₂O₄/S-GO/G on a flexible paper substrate surface demonstrated remarkable capabilities for determining Glu levels in artificial sweat samples. SPEs prepared with conductive ink produced by using these materials are promising candidates for use as electrodes in flexible and wearable sensor technology.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1451-1465"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363165","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":"Graphene Quantum Dots as Antifibrotic Therapy for Kidney Disease.","authors":"Lilin Li, Wencheng Jin, Juhee Kim, Gaeun Bae, Seung Hee Yang, Bogyeong Cho, Seung Hyun Han, Jeonghwan Lee, Donghoon Kim, Dong Ki Kim, Chun Soo Lim, Byung Hee Hong, Jung Pyo Lee","doi":"10.1021/acsabm.4c01053","DOIUrl":"10.1021/acsabm.4c01053","url":null,"abstract":"<p><p>Graphene quantum dots (GQDs) have received much attention for their biomedical applications, such as bioimaging and drug delivery. Additionally, they have antioxidant and anti-inflammatory properties. We used GQDs to treat renal fibrosis and confirmed their ability to protect renal cells from excessive oxidative stress in vitro and in vivo. Tubulointerstitial fibrosis was induced by unilateral ureteral obstruction (UUO) in 7- to 8-week-old male C57BL/6 mice. GQDs were administered by intravenous injection to mimic clinical treatment. The levels of oxidative stress, ROS production, apoptosis and proinflammatory cytokines and the activity of the TGFβ1/Smad pathway were evaluated after treatment with GQDs. In vitro, rhTGF-β1 was used to induce fibrosis in primary kidney tubule epithelial cells. GQDs alleviated fibrosis and morphological changes after UUO induction. At the mRNA and protein levels, GQDs significantly reduced the expression of fibrotic markers and proinflammatory cytokines, decreased ROS production and TGF-β1 expression, and affected Smad-dependent signaling pathways. In vitro, GQDs inhibited rhTGF-β1-induced epithelial-to-mesenchymal transition in primary kidney tubule epithelial cells and reduced apoptosis and ROS accumulation. This study revealed the role of GQDs in kidney fibrosis: GQDs effectively attenuated major fibrogenesis events by inhibiting ROS accumulation and the vicious cycle of the ROS and TGF-β1/Smad signaling pathways, as well as alleviating cell apoptosis and inflammation. Thus, GQDs may be a therapeutic option for chronic kidney disease progression.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"980-991"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995971","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":"2-Propanol Suspension Method to Increase Acetylcholinesterase and Flow Stability on μPADs.","authors":"Akinori Yamaguchi, Shota Oyama, Akihiko Ishida, Takanori Enomoto, Nobuyuki Sanari, Hajime Miyaguchi, Manabu Tokeshi","doi":"10.1021/acsabm.4c01879","DOIUrl":"10.1021/acsabm.4c01879","url":null,"abstract":"<p><p>Ensuring detection performance and shelf life is crucial for analytical devices. Advances in materials and reaction mechanisms have improved detection performance, yet extending the operational lifetime of microfluidic paper-based analytical devices (μPADs)─especially those reliant on sensitive enzymes─remains a challenge. Here, we present an alternative to air-drying and lyophilization: loading enzymes suspended in 2-propanol (iPrOH). By suspending the enzyme in iPrOH, we circumvent the enzyme activity losses commonly associated with freeze-thawing and freeze-drying. Accelerated aging tests, supported by statistical analyses of long-term activity retention (including comparisons over multiple time points), indicate that while conventional methods do not sustain consistent superiority, the iPrOH suspension method maintains higher enzymatic activity over extended periods. By avoiding stabilizers and circumventing the limitations of other techniques, our method enables μPADs to achieve both longevity and stable fluid flow. Thus, we provide a more robust, on-site analytical platform capable of reliable on-site detection.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1699-1706"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027426","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":"Fabrication of Hypoxia-Mimicking Supramolecular Hydrogels for Cartilage Repair.","authors":"Subhashini Ravi, L P Pavithra Chokkakula, Suhash Ranjan Dey, Subha Narayan Rath","doi":"10.1021/acsabm.4c01576","DOIUrl":"10.1021/acsabm.4c01576","url":null,"abstract":"<p><p>Despite advancements in chronic arthritis treatment, there remains a significant demand for advanced nanotechnologies capable of efficiently delivering a wide range of therapeutic agents to provide symptomatic relief and facilitate the healing of inflamed cartilage tissue. Considering the significant impact of hypoxia on the development and maintenance of chondral tissue, replicating its effects on stem cells could be a potential approach for the treatment of osteoarthritis (OA). Cobalt is a prominent hypoxia-inducing agent, owing to its ability to activate the hypoxia-inducible factor (HIF) pathway regardless of cellular oxygen levels. The intra-articular (IA) injection of dexamethasone (Dex) is often used to alleviate inflammation and pain associated with OA. Nevertheless, several obstacles impede the drug's efficacy, including its short duration of action and rapid elimination from the joint space. Considering these research problems, the study brings an advanced strategy for the development of a three-dimensional (3D) bioprintable hypoxia-mimicking supramolecular hydrogel (HMSG) through the self-assembly of Dex-loaded poly(ethylene glycol) diacrylate (PEGDA) guest polymers with acryloyl β-cyclodextrin (AβCD) host monomers, in combination with cobalt nanowires (Co NWs). Through the process of photo-cross-linking, HMSG can generate multivalent host-guest nanoclusters, making it an excellent candidate for 3D bioprinting, showcasing remarkable mechanical properties. By effectively delivering Dex and Co²⁺ in a sustained manner, the HMSG affords a suitable microenvironment for the encapsulated umbilical cord-derived mesenchymal stem cells (UMSCs), thereby promoting the synthesis of matrix components and decreasing the release of catabolic factors. Moreover, the HMSG ameliorates OA severity by increasing the M2 macrophage polarization, which can ultimately contribute to immunomodulatory effects. In conclusion, the results propose potential approaches for utilizing HMSG as efficient carriers to transport various therapeutic molecules to the injury site, thereby assimilating into nearby tissues and promoting successful tissue repair without the need for external growth factors.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1261-1277"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050953","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":"Osteopontin Facilitated Dental Pulp Cell Adhesion and Differentiation: A Laboratory Investigation.","authors":"Jia Tang, Youjing Qiu, Zehan Li","doi":"10.1021/acsabm.4c01616","DOIUrl":"10.1021/acsabm.4c01616","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the effects of osteopontin (OPN) on cultured human dental pulp cells (hDPCs) in relation to adhesion, proliferation, differentiation, and mineralization.</p><p><strong>Methodology: </strong>Subcultured hDPCs isolated from healthy human wisdom teeth were inoculated on noncoated (NC, control) and OPN-coated nontissue culture-treated polystyrene plates (Non-TCPS). Cell adhesion and proliferation were analyzed by crystal violet staining and the CCK-8 assay, respectively. Expressions of cell adhesion-related protein markers such as FAK and Akt were visualized by the Western blot. Expressions of tooth-related mRNA markers were evaluated by qRT-PCR. The localization of the OPN protein in reparative dentine formation was visualized using immunofluorescence staining. Data were analyzed using the Tukey's multiple comparison test.</p><p><strong>Results: </strong>Cell adhesion was significantly higher in OPN 1 μg/mL-coated group of the OPN, which is also comparable to that of the positive control (COL-1 group). Cell proliferation data showed a similar tendency. pFAK was activated as early as 3 h after cell inoculation in the 1 μg/mL-coated group of the OPN and COL-1 group. Moreover, the OPN stimulated hDPC mineralization in a time- and dose-dependent manner. Regarding the qPCR results, it was shown that OPN stimulated DMP-1 and <i>DSPP</i> expression on days 10 and 14. The RNA sequencing data implicated that the OPN promoted the gene expression of HLA-DRA, CD74, ENSG00000283390, MRPL53, NOP2, and KRTAP1-3. Finally, pulp exposure wound healing in SD rats showed that OPN expression was primarily localized in the forming reparative dentine instead of formed reparative dentine.</p><p><strong>Conclusion: </strong>Coated OPN promoted hDPC adhesion, proliferation, differentiation, and mineralization.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1320-1329"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044848","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":"Electrospun Chitosan/Polylactic Acid Nanofibers with Silver Nanoparticles: Structure, Antibacterial, and Cytotoxic Properties.","authors":"Yevhen Samokhin, Yuliia Varava, Kateryna Diedkova, Ilya Yanko, Valeriia Korniienko, Yevheniia Husak, Igor Iatsunskyi, Vladlens Grebnevs, Maris Bertiņs, Rafal Banasiuk, Viktoriia Korniienko, Agne Ramanaviciute, Maksym Pogorielov, Arunas Ramanavicius","doi":"10.1021/acsabm.4c01252","DOIUrl":"10.1021/acsabm.4c01252","url":null,"abstract":"<p><p>Electrospinning, a technique for creating fabric materials from polymer solutions, is widely used in various fields, including biomedicine. The unique properties of electrospun fibrous membranes, such as large surface area, compositional versatility, and customizable porous structure, make them ideal for advanced biomedical applications like tissue engineering and wound healing. By considering the high biocompatibility and well-known regenerative potential of polylactic acid (PLA) and chitosan (CH), as well as the versatile antibacterial effect of silver nanoparticles (AgNPs), this study explores the antibacterial efficacy, adhesive properties, and cytotoxicity of electrospun chitosan membranes with a unique nanofibrous structure and varying concentrations of AgNPs. Silver nanoparticles incorporated at concentrations of 25-50 μg/mL or above significantly enhanced the antibacterial effectiveness, especially against <i>Staphylococcus aureus</i> and <i>Escherichia coli</i>. Biocompatibility assessments using umbilical cord mesenchymal stem cells demonstrated the nontoxic nature of the membranes with an AgNP concentration of 12.5 μg/mL, underscoring their potential for biomedical applications. This study provides valuable insights into developing electrospun chitosan membranes as effective antimicrobial coatings for various biomedical uses, including wound healing patches and tissue engineering constructs for soft tissue replacement.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1027-1037"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981962","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":"Polysaccharide-Based Self-Healing Hydrogel for pH-Induced Smart Release of Lauric Acid to Accelerate Wound Healing.","authors":"Chelladurai Karthikeyan Balavigneswaran, Manoj Kumar Sundaram, Venkatesan Ramya, Karuppiah Prakash Shyam, Iniyan Saravanakumar, Balamuthu Kadalmani, Sharanya Ramkumar, Sowmya Selvaraj, Ponrasu Thangavel, Vignesh Muthuvijayan","doi":"10.1021/acsabm.4c01668","DOIUrl":"10.1021/acsabm.4c01668","url":null,"abstract":"<p><p>It is highly desirable yet significantly challenging to fabricate an injectable, self-healing, controlled-release wound dressing that is responsive to the alkaline pH of the wounds. Herein, we propose a facile approach to prepare pH-responsive chitosan-oxidized carboxymethyl cellulose (CS-o-CMC) hydrogel constructs in which gelation was achieved via electrostatic and Schiff base formation. Importantly, the Schiff base was formed in acidic medium and the final pH of pregel solution was intrinsically raised to 7.0-7.4 due to the cross-linking by β-glycerol phosphate. The self-healing behavior of the hydrogel was an enthalpy-driven process and efficient in alkaline compared to acidic pH. The pH responsiveness offered a controlled release of lauric acid (LA) from CS-o-CMC/LA hydrogel and regulated the M2 polarization. Overall, reduction in inflammation led to rapid vascularization, reepithelialization, and significantly accelerated wound healing in rats. Our findings demonstrate a promising strategy for developing injectable, immunomodulatory wound dressings tailored to the challenging environment of wounds.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1343-1361"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187537","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":"An Injectable Alginate Hydrogel Modified by Collagen and Fibronectin for Better Cellular Environment.","authors":"Daqian Gao, William D Shipman, Yaping Sun, Weijun Yang, Angelin Tresa Mathew, Leleda Beraki, Joshua Zev Glahn, Alejandro Kochen, Themis R Kyriakides, Valerie Horsley, Henry C Hsia","doi":"10.1021/acsabm.4c01853","DOIUrl":"10.1021/acsabm.4c01853","url":null,"abstract":"<p><p>Encapsulating fibroblasts in alginate hydrogels is a promising strategy to promote wound healing. However, improving the cell function within the alginate matrix remains a challenge. In this study, we engineer an injectable hydrogel through mixing alginate function with collagen and fibronectin, creating a better microenvironment for enhancing fibroblast function and cytokine secretion. We systematically analyze microstructure, mechanical properties, and fibroblast behavior of the developed hydrogel and compare it to alginate control. Our results demonstrate that inclusion collagen and fibronectin lead to the formation of fibrils on macroporous structures with pore sizes ranging from 100 to 500 μm. Compared to collagen hydrogel, the composite hydrogel shows approximately 12-fold increase in storage modulus. After encapsulating fibroblasts into the modified hydrogels, we observed increased fibroblast spreading, proliferation, and cytokine secretion when compared to neat alginate hydrogel. In addition, VEGF secretion of encapsulated fibroblasts is upregulated, indicating its pro-angiogenic potential. These findings suggest that the alginate/collagen/fibronectin hydrogel-encapsulated fibroblasts might serve as a promising therapeutic approach for wound healing.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1675-1683"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062112","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":"Host-Directed Therapy with Inhalable Lovastatin Microspheres for Matrix Metalloproteinase Inhibition in Tuberculosis.","authors":"Agrim Jhilta, Krishna Jadhav, Rahul Sharma, Raghuraj Singh, Swarnima Negi, Neelesh Sharma, Amit Kumar Singh, Rahul Kumar Verma","doi":"10.1021/acsabm.4c01723","DOIUrl":"10.1021/acsabm.4c01723","url":null,"abstract":"<p><p>Tuberculosis (TB) triggers a robust immune response, which leads to significant destruction of the lung tissue at the site of infection, aiding in the transmission of <i>Mycobacterium tuberculosis</i> (Mtb) to the hosts. The excessive inflammatory response contributes heavily to extracellular matrix (ECM) damage, which is linked to high mortality rates among TB patients. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, are pivotal in the breakdown of the ECM, worsening tissue destruction. In the context of host-directed therapy (HDT), a strategy aimed at modulating the immune response rather than directly targeting the pathogen, we evaluated the potential of lovastatin (LOV). LOV has shown promise in reducing MMP activity and inflammation, which could alleviate the immune-mediated pathology in TB. However, its clinical use has been limited due to poor solubility and biocompatibility, reducing its therapeutic efficacy. To overcome these limitations, we designed inhalable gelatin microspheres (GA-MS) loaded with LOV using the spray-drying technology. This approach improved the solubility and allowed for the controlled release of the drug. The resulting LOV-loaded gelatin microspheres (LOV/GA-MS) had an optimal particle size of 2.395 ± 0.67 μm, facilitating macrophage uptake due to their aerodynamic properties. In <i>in vitro</i> studies using Mtb-infected macrophages, LOV/GA-MS effectively suppressed MMP expression and reduced levels of pro-inflammatory cytokines at a concentration of 20 μg/mL, demonstrating substantial anti-inflammatory potential. Moreover, these microspheres showed a synergistic effect when combined with standard anti-TB drugs, enhancing the overall therapeutic efficacy in <i>in vitro</i> experiments. The findings suggest that inhalable LOV/GA-MS microspheres represent a promising adjunctive host-directed therapy for TB. By modulating the host's immune response and targeting key inflammatory mediators such as MMPs, this approach could mitigate lung tissue damage, improve clinical outcomes, and provide a more holistic treatment option for TB.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":"1533-1546"},"PeriodicalIF":4.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995973","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}