ACS Applied Bio Materials最新文献

{"title":"Advanced Nanoenabled Microalgae Systems: Integrating Oxidative Stress-Induced Metabolic Reprogramming and Enhanced Lipid Biosynthesis for Next-Generation Biofuel Production.","authors":"Luis Pablo Salmeron Covarrubias, Kavitha Beluri, Yasaman Mohammadi, Nusrat Easmin, Oskar A Palacios, Hamidreza Sharifan","doi":"10.1021/acsabm.5c00300","DOIUrl":"https://doi.org/10.1021/acsabm.5c00300","url":null,"abstract":"<p><p>The growing demand for renewable energy has positioned microalgae, such as <i>Chlorella vulgaris</i>, as a promising feedstock for sustainable biofuel production. Leveraging nanotechnology, this study explores the multifaceted impacts of zinc oxide (ZnO) nanoparticles (NPs) on <i>C. vulgaris</i>, focusing on lipid biosynthesis, oxidative stress, biomass productivity, and photosynthetic pigment retention. The morphology of NPs and algae and their interactions were extensively studied using scanning electron microscopy (SEM), confocal microscopy, energy-dispersive X-ray spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). The ZnO NP-enabled microalgae system enhanced lipid accumulation to as high as 48% at 50 mg/L. Biomass production and pigment content remained stable within the applied dose of NPs (20-50 mg/L), highlighting the resilience of <i>C. vulgaris</i> under NP exposure. However, at 100 mg/L, photosynthetic efficiency was disrupted, pigment content was reduced, and lipid yield declined to 30%. The enzymatic activity of catalase (CAT) revealed significant upregulation at higher ZnO NP concentrations, further corroborating the stress-induced metabolic shifts. This study also introduced a model for the Biofuel Suitability Score (BSS), which integrates lipid content, biomass productivity, oxidative stress levels, and pigment retention to identify the optimal conditions for biofuel production. The BSS peaked at moderate ZnO NP concentrations (30-50 mg/L), indicating a balance between lipid biosynthesis and cellular integrity. Beyond this threshold, oxidative damage compromises the biofuel potential, emphasizing the critical need for precise control of NP exposure. These findings highlight the potential of ZnO NPs to induce lipid accumulation through targeted stress modulation while maintaining biomass quality, advancing the application of nanotechnology in sustainable bioenergy systems. This study provides a scalable framework for integrating nanotechnology into renewable energy.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810020","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":"Redefining Medical Applications with Safe and Sustainable 3D Printing.","authors":"Sadaf Bashir Khan, Syed Irfan, Zhengjun Zhang, Weifeng Yuan","doi":"10.1021/acsabm.4c01923","DOIUrl":"https://doi.org/10.1021/acsabm.4c01923","url":null,"abstract":"<p><p>Additive manufacturing (AM) has revolutionized biomedical applications by enabling personalized designs, intricate geometries, and cost-effective solutions. This progress stems from interdisciplinary collaborations across medicine, biomaterials, engineering, artificial intelligence, and microelectronics. A pivotal aspect of AM is the development of materials that respond to stimuli such as heat, light, moisture, and chemical changes, paving the way for intelligent systems tailored to specific needs. Among the materials employed in AM, polymers have gained prominence due to their flexibility, synthetic versatility, and broad property spectrum. Their adaptability has made them the most widely used material class in AM processes, offering the potential for diverse applications, including surgical tools, structural composites, photovoltaic devices, and filtration systems. Despite this, integrating multiple polymer systems to achieve multifunctional and dynamic performance remains a significant challenge, highlighting the need for further research. This review explores the foundational principles of AM, emphasizing its application in tissue engineering and medical technologies. It provides an in-depth analysis of polymer systems, besides inorganic oxides and bioinks, and examines their unique properties, advantages, and limitations within the context of AM. Additionally, the review highlights emerging techniques like rapid prototyping and 3D printing, which hold promise for advancing biomedical applications. By addressing the critical factors influencing AM processes and proposing innovative approaches to polymer integration, this review aims to guide future research and development in the field. The insights presented here underscore the transformative potential of AM in creating dynamic, multifunctional systems to meet evolving biomedical and healthcare demands.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810070","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":"Near-Infrared Light-Controlled Nitric Oxide Delivery Combined with In Situ Activated Chemotherapy for Enhanced Multimodal Therapy.","authors":"Bing Ren, Jing Liu, Yi Wang, Qi Tang, Jian Fang, Shiping Yang, Jin-Gang Liu","doi":"10.1021/acsabm.5c00175","DOIUrl":"https://doi.org/10.1021/acsabm.5c00175","url":null,"abstract":"<p><p>Development of nanoplatforms with in situ activation for chemotherapy represents a promising modality for biomedical application. Herein, a multifunctional nanoplatform, CMS@DTC@PDA@RuNO@FA (abbreviated as CDPNF NPs), was developed for highly efficient antitumor therapy, in which diethyldithiocarbamate (DTC)-loaded mesoporous Cu₂MoS₄ (CMS) nanoparticles were covered by polydopamine (PDA) layers and further covalently modified with a NO donor (RuNO) and a folic acid (FA)-directing moiety. Under the mild acidic tumor microenvironment (TME), the CDPNF NPs co-liberated DTC and Cu²⁺ in the tumor site, where in situ formation of the highly cytotoxic Cu(DTC)₂ complex effectively killed tumor cells. Furthermore, under near-infrared (NIR) light irradiation, the CDPNF NPs could deliver nitric oxide (NO) and produce superoxide anions (O₂^•-), followed by the formation of more toxic peroxynitrite (ONOO^-), which led to promoted cell apoptosis. Under 1064 nm NIR light irradiation, in vivo experiments with CDPNF NPs demonstrated an impressively high tumor inhibition rate (∼97%) while with good biocompatibility. This work represents an in situ activated approach for precision medicine that might imply its promising potential for clinical applications.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801985","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":"Unravelling the Biomolecular Interactions Between Hemoglobin and 2D MXenes: A Breakthrough in Biomedical Approach.","authors":"Pooja Yadav, Muruganantham Rethinasabapathy, Diksha Dhiman, Yu Jung Choi, Yun Suk Huh, Pannuru Venkatesu","doi":"10.1021/acsabm.5c00068","DOIUrl":"https://doi.org/10.1021/acsabm.5c00068","url":null,"abstract":"<p><p>Taking the potential applications of two-dimensional transition metal carbides, such as MXenes, in biomedical fields, it is crucial to explore the impact of MXenes on various blood proteins. The study of the interaction of these 2D materials with proteins is scarce. Owing to the potential of absorbing proteins on the MXene surface, it is crucial to investigate the biocompatibility of these materials with proteins . In this regard, we successfully investigated the biomolecular interactions between hemoglobin (Hb) and single-layered titanium carbide (Ti₃C₂T<i>_x</i>-SL), multilayered titanium carbide (Ti₃C₂T<i>_x</i>-ML), and multilayered vanadium carbide (V₂CT_<i>x</i>-ML) MXenes for protein-MXene corona formation. The conformational, thermal, and colloidal stabilities of Hb were investigated after exposing MXenes to Hb for 30 min at Hb/MXene ratios of 12:1, 10:1, 8:1, and 6:1 using a combination of spectroscopic techniques, electron microscopy, and thermodynamic stability studies. Our results reveal that Hb adsorption onto MXene surfaces is primarily driven by electrostatic interactions and hydrogen bonding, leading to significant changes in the secondary and tertiary structures of the protein and further disruption in the colloidal stability of Hb. Explicitly, the hierarchy of interactions between Hb and MXenes follows the order: Ti₃C₂T<i>_x</i>-SL > V₂CT_<i>x</i>-ML > Ti₃C₂T<i>_x</i>-ML. The morphological study of Hb with MXenes was studied through transmission electron microscopy (TEM) and atomic force microscopy (AFM). Further, it was found that at high loading concentrations that is above 8:1, the protein-corona formation tendency of Hb-MXene also increases. The biological and toxicological behavior of nanomaterials (NMs) is based on the effect of their interaction with proteins, which induces conformational changes in proteins and subsequently alters their biological functions. In this regard, this article provides important insights for using these MXenes biomedically and for the rational design of nanoproducts based on MXenes in the near future.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810097","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":"Near-Infrared Multifunctional Antitumor Nanomaterial of Bismuth Sulfide Heterojunction Coupled with Mesoporous Polydopamine.","authors":"Juanxuan Guo, Biling Chen, Menglong Zhao, Wenbin Chen, Siqi Qiu, Ming-De Li, Li Dang","doi":"10.1021/acsabm.5c00313","DOIUrl":"https://doi.org/10.1021/acsabm.5c00313","url":null,"abstract":"<p><p>Bismuth sulfide@bismuth nanorods (Bi₂S₃@Bi NRs) have emerged as promising photodynamic therapeutic agents due to Bi₂S₃@Bi being able to produce reactive oxygen species from self-supplied O₂. Combining photothermal and photodynamic therapies with chemotherapy is attractive but difficult to achieve. Here, we develop a subtle method to wrap Bi₂S₃@Bi NRs with photothermal mesoporous polydopamine, where chemotherapy drug doxorubicin hydrochloride can be loaded, thus providing multifunctional antitumor nanospheres. To our delight, the prepared triple-functional material exhibits excellent antitumor efficacy toward tumor cells under near-infrared light irradiation. This multifunctional antitumor nanomaterial is not only biocompatible but also suitable for tumor hypoxic microenvironments, having much better efficacy than single- or double-functional materials. This study highlights the great potential of combining photothermal, photodynamic, and chemotherapies.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810046","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":"Deep-Red Cyanine-Based Fluorescent Probes with 6-Quinolinium Acceptors for Mitochondrial NAD(P)H Imaging in Live Cells and Human Diseased Kidney Tissues.","authors":"Dilka Liyana Arachchige, Sushil K Dwivedi, Peter Agyemang, Henry Lanquaye, Joseph Peters, Grace Rickauer, Ashlyn Colleen Beatty, Matthew Plansinis, Yan Zhang, Athar Ata, Thomas Werner, Haiying Liu","doi":"10.1021/acsabm.5c00015","DOIUrl":"https://doi.org/10.1021/acsabm.5c00015","url":null,"abstract":"<p><p>We developed two deep-red cyanine chromophores, probes <b>A</b> and <b>B</b>, for selective mitochondrial NAD(P)H detection in live cells. Probe <b>A</b> features a 1,2,3,3-tetramethyl-3H-indolium core, while probe <b>B</b> incorporates a 1,1,2,3-tetramethyl-1H-benzo[e]indol-3-ium moiety, both linked to quinolinium via a vinyl bond to enable fluorescence modulation upon NAD(P)H reduction of probes <b>A</b> and <b>B</b>. To explore the role of electron-withdrawing groups in probe sensitivity, we synthesized three additional cyanine dyes (probes <b>C</b>, <b>D</b>, and <b>E</b>) via condensation of 6-quinolinecarboxaldehyde with 2,3-dimethyl-1,3-benzothiazolium acceptor and malononitrile derivatives, followed by methylation. Under NAD(P)H-deficient conditions, probe <b>A</b> showed absorption at 382 nm with weak fluorescence at 636 nm, while probe <b>B</b> absorbed at 443 nm with weak fluorescence at 618 nm. Upon NAD(P)H reduction, probe <b>A</b> exhibited red-shifted absorption at 520 nm with enhanced emission at 589 nm, and probe <b>B</b> at 550 nm with strong emission at 610 nm. Probe <b>C</b> showed absorption at 524 nm with enhanced emission at 586 nm, while probes <b>D</b> and <b>E</b> exhibited no detectable NAD(P)H response, highlighting the critical role of quinolinium acceptors. Probe <b>B</b> demonstrated superior sensitivity, successfully tracking NAD(P)H fluctuations in HeLa cells under glycolysis stimulation (glucose, lactate, pyruvate) and treatments with LPS and methotrexate. It also visualized NAD(P)H in <i>Drosophila</i> larvae, revealing increased levels after drug treatments. Notably, probe <b>B</b> distinguished between healthy and diseased human kidney tissues, detecting significantly elevated NADH levels in autosomal dominant polycystic kidney disease (ADPKD) samples, emphasizing its diagnostic potential. This study introduces probe <b>B</b> as a versatile and reliable NAD(P)H sensor for metabolic research and disease diagnostics, offering valuable insights into redox processes in live cells, organisms, and clinical samples.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801954","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":"Methemoglobin-Encapsulating Liposome: A Low-Risk Intravascular Contrast Agent for Magnetic Resonance Imaging.","authors":"Kazuaki Taguchi, Akira Sumiyoshi, Yuto Suzuki, Yoshikazu Ozawa, Megumi Iiyama, Shan Gao, Hiromi Sakai, Kensuke Osada, Kazuaki Matsumoto, Ichio Aoki","doi":"10.1021/acsabm.4c01451","DOIUrl":"https://doi.org/10.1021/acsabm.4c01451","url":null,"abstract":"<p><p>Hemoglobin shows different contrasts on magnetic resonance imaging (MRI) depending on the iron and oxygenation states of heme. Functional brain MRI utilizes the differences in the concentrations of oxyhemoglobin and deoxyhemoglobin in cerebral blood vessels; blood clots produce strong magnetic susceptibility effects. We hypothesized that methemoglobin (MetHb)-based nanoparticles can act as MRI contrast agents because MetHb levels in red blood cells affect relaxivity and are strictly regulated to <1% in the blood. Herein, we describe the synthesis of methemoglobin-encapsulated liposomes (Met-HbVs) as contrast agents for MRI. Met-HbV, with a size of approximately 200 nm, increased longitudinal relaxivity (<i>r</i>₁) by 2.44-fold compared with hemoglobin-encapsulated liposomes <i>in vitro</i>. In contrast, the transverse relaxation capacity (<i>r</i>₂) of Met-HbVs was similar to that of the hemoglobin-encapsulated liposomes. Owing to its relaxivity, Met-HbV enhanced the signal intensity on T1-weighted images and angiography, especially in the veins. Furthermore, deleterious biological responses were seldom observed after Met-HbV administration in mice with chronic renal failure. In conclusion, Met-HbV possesses potential as a vascular contrast agent in MRI for angiography, with advantages over gadolinium-based contrast agents in terms of safety for patients with renal failure. To the best of our knowledge, this is the first report demonstrating the potential of MetHb as a biomaterial for contrast agents in MRI.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801981","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":"Multilayer Film with Bioactive and Antiadhesive Layers for Accelerated Tendon Regeneration.","authors":"Ho Yong Kim, Seung Hyeon Cho, Min Ji Kim, Myung-Keun Song, Sang-Youn Song, Dong-Hee Kim, Se Heang Oh","doi":"10.1021/acsabm.5c00131","DOIUrl":"https://doi.org/10.1021/acsabm.5c00131","url":null,"abstract":"<p><p>Despite advances in surgical techniques for tendon injuries and improvements in rehabilitation, the challenge of achieving sufficient tendon regeneration and preventing postoperative tissue adhesions persists for orthopedic surgeons. In this study, we developed a multilayer film with a platelet-derived growth factor-BB (PDGF-BB)-immobilized leaf-stacked structure (LSS) layer (bioactive layer) and an alginate layer (antiadhesive layer) on both sides of a PCL film (<i>PDGF/FLSS-Alg</i>). The porous LSS layer on the PCL film was fabricated using a heating-cooling method with tetraglycol, where PDGF-BB was adsorbed onto the LSS layer. An alginate coating was applied on the opposite side to form the antiadhesion layer. The PDGF-BB loaded on the LSS layer provided a sustained release at effective concentrations for over 29 days. From in vitro cell culture and in vivo animal studies, the alginate layer proved effective in preventing cell/tissue adhesion; meanwhile, the bioactive layer facilitated tenogenic differentiation in <i>h</i>BMSCs and supported tendon regeneration. Accordingly, we propose that <i>PDGF/FLSS-Alg</i> offers a viable strategy for effective tendon regeneration in clinical practice.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801983","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":"Injectable Hydrogel Technologies for Bone Disease Treatment.","authors":"Ahmed M Salama, John G Hardy, Abdurohman Mengesha Yessuf, Jianbin Chen, Ming Ni, Cheng Huang, Qidong Zhang, Yong Liu","doi":"10.1021/acsabm.4c01968","DOIUrl":"https://doi.org/10.1021/acsabm.4c01968","url":null,"abstract":"<p><p>Injectable hydrogels represent a highly promising approach for localized drug delivery systems (DDSs) in the management of bone-related conditions such as osteoporosis, osteonecrosis, osteoarthritis, osteomyelitis, and osteosarcoma. Their appeal lies in their biocompatibility, adjustable mechanical properties, and capacity to respond to external stimuli, including pH, temperature, light, redox potential, ionic strength, and enzymatic activity. These features enable enhanced targeted delivery of bioactive agents. This mini-review evaluates the synthesis of injectable hydrogels as well as recent advancements for treating a range of bone disorders, focusing on their mechanisms as localized and sustained DDSs for delivering drugs, nanoparticles, growth factors, and cells (e.g., stem cells). Moreover, it highlights their clinical studies for bone disease treatment. Additionally, it emphasizes the potential synergy between injectable hydrogels and hydrogel-based point-of-care technologies, which are anticipated to play a pivotal role in the future of bone disease therapies. Injectable hydrogels have the potential to transform bone disease treatment by facilitating precise, sustained, and minimally invasive therapeutic delivery. Nevertheless, significant challenges, including long-term biocompatibility, scalability, reproducibility, and precise regulation of drug release kinetics, must be addressed to unlock their clinical potential fully. Addressing these challenges will not only advance bone disease therapy but also open new avenues in regenerative medicine and personalized healthcare.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143801979","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":"Noninvasive Transdermal Delivery of STING Agonists Reshapes the Immune Microenvironment of Melanoma and Potentiates Checkpoint Blockade Therapy Efficacy.","authors":"Junjie Zhang, Hui Yang, Liang Li, Changkun Peng, Jingying Li","doi":"10.1021/acsabm.4c02004","DOIUrl":"https://doi.org/10.1021/acsabm.4c02004","url":null,"abstract":"<p><p>The emergence of immunotherapy as a revolutionary therapeutic modality has fostered confidence and underscored its potent efficacy in tumor therapy. However, enhancing the therapeutic efficacy of immunotherapy by precise and judicious administration poses a significant challenge. In this context, we have developed a disulfide-bearing transdermal nanovaccine by integrating a thiol-reactive agent lipoic acid (LA) into a metal-coordinated cyclic dinucleotide nanoassembly, designated as LA-Mn-cGAMP (LMC) nanovaccines. Upon topical application to the skin with melanoma, the dithiolane moiety of LA enables thiol-disulfide dynamic exchange in the skin, hence facilitating penetration into both the skin and subcutaneous tumor tissues via the thiol-mediated uptake (TMU) mechanism. Our findings demonstrate that transdermal administration of LMC significantly enhances STING activation, mitigates the immunosuppressive tumor microenvironment (TME), and retards melanoma progression. Moreover, the remodeled TME amplifies the efficacy of immune checkpoint inhibitors. This advancement offers an administration strategy for existing STING agonist therapy, potentially improving the biosafety of immunotherapy.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794010","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}