ACS nano medicine最新文献

{"title":"Precision Temperature Control of Volume Phase Transition in Biocompatible PEG-Based Nanogels for Triggered Drug Release.","authors":"Sofia Patri, Saanchi Agrawal, Paul Joseph Kempen, Nguyen Thi Kim Thanh, Nazila Kamaly","doi":"10.1021/acsnanomed.6c00111","DOIUrl":"10.1021/acsnanomed.6c00111","url":null,"abstract":"<p><p>Thermoresponsive nanogels (NGs) can reversibly alter their structure in response to temperature changes. This enables controlled drug release, targeted therapy, and improved treatment precision under physiological or externally applied thermal conditions. Despite these advantages, few studies have systematically tuned the volume phase transition temperature (VPTT) of oligo-(ethylene glycol) methacrylates (OEGMA)-based NGs across physiologically relevant temperatures while maintaining stability and biodegradability. In this work, NGs were synthesized using di-(ethylene glycol) methyl ether methacrylate (DEGMA), tri-(ethylene glycol) methyl ether methacrylate (TEGMA), and 2-methoxyethyl methacrylate (MOEMA) monomers, achieving finely tuned VPTT with a precision within 1 °C. The NGs exhibited diameters ranging from 200 to 350 nm and a negative ζ-potential. Upon reaching the VPTT, the NGs shrank to sizes below 100 nm while becoming monodisperse. Specifically, NG@TEGMA exhibited VPTT between 50-60 °C, NG@DEGMA between 30-45 °C, and NG@TEGMA_DEGMA between 64-66 °C, and NG@TEGMA_MOEMA with molar ratios of 40%, 30%, and 20% displayed VPTT of 37, 47, and 52 °C, respectively. NG@TEGMA NGs were further polymerized with a methacrylated docetaxel derivative, achieving an encapsulation efficiency of 93 ± 4%. These NGs released approximately 90% of the drug upon reaching the VPTT, while nonthermoresponsive controls only released about 20% of the drug. Furthermore, NG@TEGMA demonstrated negligible cytotoxicity and efficient cellular uptake. This study demonstrates a biocompatible and degradable platform of OEGMA-based thermoresponsive NGs for biomedical applications such as hyperthermia-driven drug delivery for cancer therapy with superior thermoresponsive behavior to previously reported OEGMAs-, NIPAM-, or VCL-based NGs.</p>","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 6","pages":"1469-1483"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428664","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}

{"title":"Micro/Nanorobots (MNRs) at the Intersection of Mechanobiology and Artificial Intelligence: An Emerging Frontier for Precision Nanomedicine.","authors":"Tahniat Afsari, Jamile Harmouch, Rahul Sharma, Ruisheng Liu, Subhra Mohapatra, Shyam S Mohapatra","doi":"10.1021/acsnanomed.5c00168","DOIUrl":"10.1021/acsnanomed.5c00168","url":null,"abstract":"<p><p>Micro/nanorobots (MNRs) are emerging as active precision-nanomedicine platforms that convert physical energy into propulsion and localized cellular or tissue mechanotransduction. Yet, the ways in which MNR-mediated forces and flows reprogram cell behavior, activate mechanotransduction pathways, or drive tissue remodeling remain poorly understood. Unlike passive nanocarriers that rely on diffusion and vascular permeability, MNRs enable directional transport, barrier penetration, and spatiotemporal control. Beyond locomotion, propulsion-induced stresses act as mechanical cues that engage cellular mechanosensing pathways, including membrane-tension regulation, ion-channel activation, cytoskeletal remodeling, and downstream intracellular transcriptional signaling. Here, we review MNRs as mechanobiology-driven systems in which propulsion physics is intentionally coupled to force-sensitive biological responses. Rather than categorizing MNRs solely by actuation modality, we propose force-to-function coupling as a unifying design principle linking propulsion dynamics to defined mechanotransduction outcomes at the nano-bio interface. We further discuss how artificial intelligence (AI) introduces predictive modeling, imaging-guided feedback, and closed-loop optimization to achieve programmable biological outputs under physiological uncertainty. This review establishes a framework for biology-aware and intelligent MNRs by integrating propulsion engineering, mechanobiology, and computational control, and highlights key translational challenges that must be addressed to realize precision nanomedicine.</p>","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 8","pages":"1706-1724"},"PeriodicalIF":0.0,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13564963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957812","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}

{"title":"Intrathecal Delivery of Macromolecules to the Spinal Cord Enabled by Laser-Activated Perfluorocarbon Nanodroplets.","authors":"Robert J Nikolai, Anthony Donsante, Jason J Lamanna, Melissa Cadena, Anamik Jhunjhunwala, David Qin, Elena V Vassilieva, Arya T Oak, Shreya Vavilala, Matthew Byrne, Nicholas M Boulis, Stanislav Y Emelianov","doi":"10.1021/acsnanomed.5c00207","DOIUrl":"10.1021/acsnanomed.5c00207","url":null,"abstract":"<p><p>The lack of safe, minimally invasive strategies for targeted drug delivery to the spinal cord remains a major barrier to treating neurodegenerative disease and spinal injury. Intrathecally administered macromolecules, including gene therapy vectors, rarely penetrate spinal tissue at therapeutically relevant concentrations due to cellular barriers at the cerebrospinal fluid-spinal cord interface. Here, we demonstrate the application of laser-activated perfluorocarbon nanodroplets (PFCnDs) for nonsurgical, spatially controlled delivery from the subarachnoid space into spinal cord parenchyma. Following intrathecal injection in rats, transdermal laser irradiation produced a 7-fold increase in photoacoustic signal within the spinal cord parenchyma compared to nonirradiated controls, confirming spatially selective intraparenchymal nanodroplet delivery. Codelivery of 500 kDa FITC-dextran demonstrated approximately 1 mm penetration into the dorsal horn at irradiated sites, while nonirradiated regions showed only superficial perivascular accumulation. Neither nanodroplets alone nor laser irradiation alone produced intraparenchymal delivery, indicating that vaporization-induced cavitation is necessary for penetration. The PFCnDs (∼300 nm diameter) were engineered with a lipid shell, perfluorohexane core, and near-infrared absorbing dye for transdermal activation at 1064 nm. These results demonstrate that laser-activated nanodroplets can deliver macromolecular cargo into the spinal cord via lumbar puncture and transdermal irradiation, without surgical exposure.</p>","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 6","pages":"1447-1455"},"PeriodicalIF":0.0,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428650","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}

{"title":"A Dual-Pronged Hafnia-Prodrug-Lipid Nanoplatform Coupling Radiosensitization and DNA Homologous Recombination Inhibition.","authors":"David Skrodzki, Pranay Saha, Matthew Molinaro, Nada Maher, Shraddha Krishnakumar, Nivetha Gunaseelan, Mecit Altan Alioglu, Oguzhan Colak, Gabriela Cepeda, Parikshit Moitra, Timothy M Fan, Dipanjan Pan","doi":"10.1021/acsnanomed.6c00022","DOIUrl":"10.1021/acsnanomed.6c00022","url":null,"abstract":"<p><p>Emerging nanomedicine strategies have established clinical translation and the ability to offset conventional therapeutic challenges. This study aimed to report the development and analysis of a nanoscale material that functioned as both a high-Z radiosensitizer and a prodrug delivery system. In this study, a nanoscale platform using two complementary radiosensitizing mechanisms was designed and developed to overcome nonspecific toxicity, which is a challenge in both chemotherapy and radiotherapy. High-Z physical radiosensitization was coupled with the inhibition of a critical DNA double-strand break repair mechanism, homologous recombination, through a lipid nanoparticle decorated with ultrasmall Hafnia nanoparticles and loaded with an amphiphilic prodrug. In vitro and in vivo studies demonstrated significant enhancement of therapeutic effects, cell killing, or tumor regression, respectively, versus radiation alone. These results support the use of this combination system as a practical strategy for maintaining treatment efficacy at modest doses of radiation and offset associated adverse effects.</p>","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 6","pages":"1456-1468"},"PeriodicalIF":0.0,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13352939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148428615","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}

{"title":"Nanotechnology in Cancer Therapy: How Nanoparticles Are Shaping the Future of Personalized Treatment.","authors":"Indrianita Lionadi, Amir Farokh Payam","doi":"10.1021/acsnanomed.5c00117","DOIUrl":"10.1021/acsnanomed.5c00117","url":null,"abstract":"<p><p>Nanotechnology has transformed cancer research, with nanoparticles emerging as powerful platforms for therapy and diagnosis due to their tunable physicochemical properties and biocompatibility. Nanoparticles enable targeted drug delivery, improved pharmacokinetics, and reduced systemic toxicity compared with conventional therapies while also supporting molecular imaging and theragnostic applications. More than eight nanoparticle-based formulations are currently FDA/EMA approved for oncology, highlighting the clinical relevance of nanomedicine. Despite these advances, clinical translation remains limited by biological and technical challenges, including variability in the enhanced permeability and retention effect, insufficient tumor penetration, and low manufacturing scalability. This review primarily focuses on preclinical and translational nanomedicine with selected clinical examples. We summarize recent progress in major nanocarrier classes, including liposomes and polymeric, inorganic, and hybrid nanoparticles, and their roles in cancer therapy. These findings underscore that effective nanotherapeutic strategies must be informed by tumor biology rather than relying on passive targeting alone, that combination and stimuli-responsive platforms represent the most promising therapeutic avenues, and that meaningful clinical translation will depend on overcoming tumor heterogeneity with patient-specific treatment options and achieving robust, reproducible manufacturing.</p>","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 4","pages":"871-911"},"PeriodicalIF":0.0,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13178138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966831","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}

{"title":"Nested Nanowell Arrays for High-Throughput Quantitative Analysis of Cytokines from Single Macrophages.","authors":"Claudius L Dietsche, Lucien R Stöcklin, Robert Strutt, Petra S Dittrich","doi":"10.1021/acsnanomed.5c00149","DOIUrl":"10.1021/acsnanomed.5c00149","url":null,"abstract":"<p><p>Macrophages play a critical role in the development of the tumor microenvironment (TME). Recruited macrophages in the TME differentiate into various phenotypes, each with a distinct profile of secreted cytokines. To describe and understand this large heterogeneity, we developed nested nanowell arrays for the multiplexed analysis of secreted proteins at the single cell level. The array consists of more than 100,000 wells on a cyclic olefin copolymer (COC) substrate. Each well contains seven smaller indents for cocapturing functionalized beads and can be operated with standard laboratory equipment such as pipettes and microscopes. The barcoded beads capture cytokines of interest and allow their quantification via sandwich immunoassays. We developed an image analysis tool and quantified 10 proteins secreted from single macrophages and investigated the effects of stimulation and drug treatment. We found that interleukin (IL)-1β, IL-8, and macrophage inflammatory protein 1α (MIP-1α) were highly secreted by more than 43% of the macrophages, with an increase of MIP-1α secretion under treatment with the chemotherapeutic drugs paclitaxel or docetaxel. Pairwise protein analysis confirmed cosecretion of IL-1β and IL-6 in macrophages stimulated with IL-4/IL-13, which were identified as part of a critical pathway in multiple myeloma before. We also demonstrate further multiplexing with three and four cosecreted proteins, together with assessing the cell viability as an additional parameter important for drug testing. In summary, we have shown that our nested nanowell arrays are an easy-to-use analytical tool for basic research, and we believe that it can be employed for diagnostics and personalized medicine, e.g., for investigation of cancer and immune cells from a biopsy or circulating tumor cells obtained from a liquid biopsy.</p>","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 5","pages":"1227-1238"},"PeriodicalIF":0.0,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13262127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148255490","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}

{"title":"Engineering Optimized EV-Mimetic Carriers for Efficient Tumor-Targeted Delivery of Functional RNA Nanoparticles.","authors":"Nathalia Leal Dovaizem, Laura P Rebolledo, Anh Ha, Roger Chammas, Luciana Nogueira de Sousa Andrade, Kirill A Afonin","doi":"10.1021/acsnanomed.6c00004","DOIUrl":"10.1021/acsnanomed.6c00004","url":null,"abstract":"<p><p>The therapeutic potential of RNAi is limited by the lack of safe, scalable, and efficient delivery systems. Although extracellular vesicles (EVs) are promising carriers for RNA therapeutics, poor scalability and low cargo-loading efficiency constrain their clinical translation. Here, we introduce fully synthetic EV-mimetic (EVM) carriers for the delivery of RNAi-inducing RNA nanoparticles to tumor cells. We systematically evaluated four different EVM cargo-loading strategies using representative RNA nanoparticles and appropriate controls. For each strategy, EVM size, concentration, and cargo encapsulation efficiency were assessed. Cellular uptake and RNA delivery were examined in melanoma 3D spheroids and compared with natural tumor-derived EVs, with EVMs demonstrating superior delivery efficiency. Functional RNAi activation was evaluated in tumor monolayers and 3D spheroids, where EVMs exhibited effective gene silencing with lower toxicity than conventional lipid-based carriers. Overall, our findings establish EVMs as safe and scalable biomimetic platforms for therapeutic nucleic acid delivery and identify optimal loading strategies and RNA nanoparticle designs for achieving maximal gene-silencing.</p>","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12965198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147380432","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}

{"title":"Injectable Protocatechualdehyde-Fe Nanocomposite Hydrogel Loaded with Au/Se Nanoparticles for Rapid Hemostasis and Wound Healing","authors":"Renkai Zhang, Nannan Zheng, Shuang Zhao, Q. C. Feng, Zhiyue Cao, Shuangli Zhu, K. Li, Liangcan He, Ruiwen Wang, Qiuyue Ma, Shaoqin Liu","doi":"10.1021/acsnanomed.5c00127","DOIUrl":"https://doi.org/10.1021/acsnanomed.5c00127","url":null,"abstract":"Effective wound healing remains a clinical challenge due to complications such as hemorrhage, oxidative stress, and the growing threat of antibiotic resistance. To overcome these obstacles, we have developed an injectable, dynamic hydrogel system constructed through a protocatechualdehyde-Fe3+ coordination network and adipic dihydrazide (ADH)-grafted gelatin cross-linking, further integrated with gold/selenium nanoparticles (Au/Se NPs). The dynamic catechol-Fe3+ interactions endow the hydrogel with self-healing properties and enable controlled release of embedded nanoparticles. This multifunctional hydrogel demonstrates potent antibacterial efficacy, achieving bactericidal rates exceeding 98% against E. coli and S. aureus under NIR. It also exhibits remarkable antioxidant capacity, with over 97% DPPH radical scavenging activity, alongside robust mechanical strength (withstanding 80% compressive strain at 1.09 MPa) and strong tissue adhesion (26.43 kPa). The incorporated Au/Se NPs exhibit cascade enzyme-mimetic activities, including catalase- and peroxidase-like functions, enabling continuous regulation of reactive oxygen species and oxygen generation within the wound microenvironment. This cascade catalytic behavior synergistically enhances antibacterial efficacy and mitigates oxidative stress during the early stages of wound healing. Notably, the hydrogel achieves rapid hemostasis within 50 s in a rat liver hemorrhage model. In a murine full-thickness skin wound model, the Au/Se NP-doped hydrogel promotes granulation tissue formation and collagen remodeling, significantly accelerating wound healing compared with the control group. The composite hydrogel exerts its therapeutic effects through two synergistic mechanisms: acting as a physical barrier and delivering active nanoparticles. These results highlight the potential of this hydrogel as a promising platform for rapid hemostasis and enhanced tissue regeneration in clinical wound care applications.","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 4","pages":"1000-1020"},"PeriodicalIF":0.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147877580","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":"Tumor radiosensitization with gold nanoparticles: evolving strategies to improve tumoral gold uptake and catalyze future clinical translation.","authors":"Prapannajeet Biswal, Geraldine V Vijay, Gabrielle Krouse, Phuoc Minh Quan Mai, Bhoomika Muruvekere Lakshmisha, Sanaz Keshavarz Shahbaz, Mahdieh Yousefi Taba, Aria Sabbagh, Lydia Wt Cheung, Yuri Mackeyev, Khadijeh Koushki, Sunil Krishnan","doi":"10.1021/acsnanomed.5c00110","DOIUrl":"10.1021/acsnanomed.5c00110","url":null,"abstract":"<p><p>Radiation therapy is integral to the treatment regimens of over 50% of cancer patients. However, it is not biologically targeted to just the tumor, leading to adverse effects in peritumoral normal tissue. Selective uptake of gold nanoparticles (AuNPs) by tumors realizes tumor-specific radiosensitization via increased secondary electron release from high atomic number gold atoms. Here, we review AuNP-mediated radiosensitization and outline strategies to optimize tumor-targeted AuNP delivery. Modifying the physicochemical characteristics of AuNPs, including size, shape, charge, and surface chemistry, can increase their ability to evade the reticuloendothelial system (RES) and penetrate the dense tumor stromal architecture, thereby promoting tumor accumulation. AuNPs of larger sizes readily accumulate peritumorally but are easily opsonized and cleared by the RES, whereas the smaller ones can passively internalize within tumor cells but are rapidly cleared by the kidneys. These contrasting size-dependent properties can be exploited through a size-switching strategy, whereby AuNPs reversibly aggregate or disaggregate in response to intrinsic tumor microenvironmental cues or extrinsic triggers, facilitating tumor uptake while remaining inert and RES-evasive in circulation. Stealth coatings on AuNPs like polyethylene glycol and zwitterions minimize opsonization and enhance RES evasion. Surface-functionalized AuNPs decorated with tumor-homing ligands boost selective uptake via tumor-specific receptors. Biomimetic membranes derived from native cells confer innate tumor-targeting capability and increase circulation time. These rationally designed AuNP platforms offers a promising pathway toward clinical translation.</p>","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12931844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147314746","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}

{"title":"A Strontium-Engineered FAND with Ultrahigh NAD ⁺ Loading for Targeted Therapy of Acute Lung Injury","authors":"Ruixue Liu, Pingyi Yao, Weiyu Li, Meng Sun, Yueyun Fan, Jianyu Wang, Sa Wang, Chuang Zhang, Hui Li, Jun Yang, Y. F. Wang, Jinfeng Zhang","doi":"10.1021/acsnanomed.5c00090","DOIUrl":"https://doi.org/10.1021/acsnanomed.5c00090","url":null,"abstract":"Acute lung injury (ALI) remains a devastating respiratory syndrome, with high mortality and limited therapeutic options. Herein, we report the rational design of a lung epithelial cell membrane-camouflaged full-API nanodrug (FAND) that integrates three bioactive components─bioactive trace element strontium ions (Sr2+), essential coenzyme nicotinamide adenine dinucleotide (NAD+), and FDA-approved anti-inflammatory drug dexamethasone (DEX)─into a supramolecular nanoassembly (DSN FAND@LM) with 100 wt % active pharmaceutical ingredient (API) content. Within this architecture, Sr2+ functions as a pivotal coordination hub, bridging DEX and NAD+ to achieve an ultrahigh NAD+ loading of ∼66.5%, the highest reported to date for NAD+-based nanotherapeutics. The engineered lung epithelial membrane imparts an intrinsic inflammation-homing capability, enabling precise accumulation at injured pulmonary sites. Synergistic therapeutic actions are realized through Sr2+-mediated regulation of apoptosis-associated signaling, NAD+-driven restoration of mitochondrial bioenergetics and suppression of NF-κB activation, and DEX-induced attenuation of oxidative stress. Both in vitro and in vivo studies demonstrate pronounced suppression of inflammatory cascades and enhanced lung epithelial regeneration, culminating in the accelerated repair of injured alveolar tissue. This work establishes a paradigm for FAND that codeliver Sr2+ and NAD+ for targeted, multimodal therapy of ALI and highlights a broadly translatable platform for metal ion-enabled nanotherapeutics.","PeriodicalId":521232,"journal":{"name":"ACS nano medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381532","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}