IF 17.1 1区材料科学

ACS Nano Pub Date : 2025-09-15 DOI: 10.1021/acsnano.5c09100

Chen Chen, Ana Marie Perea Del Angel, Ramya Sridharan, Daniel A. Heller

{"title":"Endolysosomal Sequestration Effects Controlled Release of BRAF Paradox Breaker Nanoparticles","authors":"Chen Chen, Ana Marie Perea Del Angel, Ramya Sridharan, Daniel A. Heller","doi":"10.1021/acsnano.5c09100","DOIUrl":"https://doi.org/10.1021/acsnano.5c09100","url":null,"abstract":"BRAF remains one of the most important therapeutic targets in cancer, but BRAF inhibitors can cause “paradoxical” pathway activation and drug resistance through RAF dimerization. A clinical “paradox breaker” inhibitor of BRAF monomers and dimers can potentially evade drug resistance. However, patients are required to receive a high oral daily drug dose to achieve the target therapeutic window. Co-administration of a cytochrome P450 blocker can improve drug exposure, but the combination can lead to drug–drug interactions. We investigated delivery via fucoidan-based nanocarriers to improve pharmacologic properties. We found that the nanoparticles extended BRAF inhibition in cancer cells due to sequestration into endolysosomes, followed by controlled release from a lysosomal depot. Following intraperitoneal administration, nanoparticles improved drug pharmacokinetics in vivo without inhibiting cytochrome P450 and also resulted in substantial improvements in antitumor efficacy. This work describes a general nanotherapeutic strategy to improve the pharmacologic properties of drugs via intracellular depot formation.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"26 1","pages":""},"PeriodicalIF":17.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Giant Photostriction and Optically Modulated Ferroelectricity in BiFeO3 BiFeO3的巨光伸缩和光调制铁电性

IF 17.1 1区材料科学

ACS Nano Pub Date : 2025-09-15 DOI: 10.1021/acsnano.5c05203

H. Zhang, M. C. Nagashree, R. F. Webster, J. Edwards, B. V. Rajendra, S. D. Kulkarni, T. Yousaf, D. Zhang, A. Gruverman, J. Seidel, P. Sharma

{"title":"Giant Photostriction and Optically Modulated Ferroelectricity in BiFeO3","authors":"H. Zhang, M. C. Nagashree, R. F. Webster, J. Edwards, B. V. Rajendra, S. D. Kulkarni, T. Yousaf, D. Zhang, A. Gruverman, J. Seidel, P. Sharma","doi":"10.1021/acsnano.5c05203","DOIUrl":"https://doi.org/10.1021/acsnano.5c05203","url":null,"abstract":"BiFeO3 thin films, with their intertwined lattice, charge, and spin orders, hold immense potential for next-generation optomechanical applications. However, their photostrictive response remains underexplored and typically demands high optical power. Here, we demonstrate a strong photostriction effect in nanocrystalline BiFeO3 thin films synthesized via scalable chemical spray pyrolysis─activated under relatively low optical powers (∼1.7 × 104 W m–2). This phenomenon is accompanied by light-driven enhancements in piezoelectricity and polarization switching together with a dense network of domain walls promoting efficient exciton separation in unconstrained nanocrystalline BiFeO3 films. The nanostructured films exhibit a photostriction coefficient of ∼4.5 × 10–7 m2 W–1─five times higher than bulk BiFeO3 single crystals and rivaling state-of-the-art halide perovskites. These findings offer valuable insights and provide a way forward for integrating solution-processed bismuth ferrite films into advanced photosensors, wireless optomechanical and multifunctional devices.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"63 1","pages":""},"PeriodicalIF":17.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Realizing Boltzmann Switching Limit in Carbon Nanotube Transistors through Combating Intertube Electrostatic Coupling 克服管间静电耦合实现碳纳米管晶体管玻尔兹曼开关极限

IF 17.1 1区材料科学

ACS Nano Pub Date : 2025-09-15 DOI: 10.1021/acsnano.5c11504

Jinshuai Lv, Hang Zhou, Zhiyi Cui, Fei Liu, Lian-Mao Peng, Chenguang Qiu

{"title":"Realizing Boltzmann Switching Limit in Carbon Nanotube Transistors through Combating Intertube Electrostatic Coupling","authors":"Jinshuai Lv, Hang Zhou, Zhiyi Cui, Fei Liu, Lian-Mao Peng, Chenguang Qiu","doi":"10.1021/acsnano.5c11504","DOIUrl":"https://doi.org/10.1021/acsnano.5c11504","url":null,"abstract":"High-density aligned carbon nanotubes (A-CNTs), with ultrahigh carrier mobility and atomically thin bodies, hold great promise for next-generation field-effect transistors (FETs), offering significant potential for high speed and energy efficiency. These unique properties position A-CNTs as a leading candidate for future very-large-scale integration technologies in the post-Moore era. However, fabricated short-channel A-CNT transistors suffer from significant off-state degradation, falling short of the requirements for sub-1 nm node technology. The underlying mechanisms for performance degradation in aligned carbon nanotube transistors are poorly understood. This study reveals that stacking in A-CNTs induces significant bandgap narrowing (BGN) in conventional single-gate transistor configurations. This effect compromises the inherent quasi-one-dimensional electrostatic advantages of A-CNTs. We propose an efficient dual-gate architecture to resist BGN and enable subthreshold swing in A-CNT transistors to reach the Boltzmann thermionic limit of 60 mV/decade, while achieving an on/off current ratio exceeding 106. Additionally, our fabricated 10 nm ultrashort-gate A-CNT DG-FETs exhibit high performance, including a saturation current exceeding 1.8 mA/μm, a peak transconductance of 2.1 mS/μm, and low static power consumption of 10 nW/μm. DG A-CNT FETs exhibit performance merits that meet the requirements of state-of-the-art integrated circuits.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"9 1","pages":""},"PeriodicalIF":17.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Edge-Selected Selenization of Subnanometer Amorphous NiFe Hydroxides for Efficient Alkaline Oxygen Evolution 亚纳米非晶NiFe氢氧化物的边选硒化研究

IF 17.1 1区材料科学

ACS Nano Pub Date : 2025-09-15 DOI: 10.1021/acsnano.5c09887

Teng Wang, Hao Wei, Renquan Hu, Nan-Nan Liang, Zhen Sun, Jiaqian Qin, Mingchuan Luo, Yong Yang

{"title":"Edge-Selected Selenization of Subnanometer Amorphous NiFe Hydroxides for Efficient Alkaline Oxygen Evolution","authors":"Teng Wang, Hao Wei, Renquan Hu, Nan-Nan Liang, Zhen Sun, Jiaqian Qin, Mingchuan Luo, Yong Yang","doi":"10.1021/acsnano.5c09887","DOIUrl":"https://doi.org/10.1021/acsnano.5c09887","url":null,"abstract":"Crystalline–amorphous (c-a) heterointerfaces are a promising strategy to upgrade nanomaterials for catalysis. However, achieving precise control over c-a heterointerfaces at the subnanometer (subnm) scale for maximizing catalytic sites remains a formidable challenge. Here, we report a dual ligand-assisted synthesis strategy to engineer a hierarchically c-a heterostructure on subnanometer NiFe hydroxide, synergizing atomic-scale structural refinement with interfacial optimization for enhanced oxygen evolution reaction (OER) performance. Through the selective selenization of unstable edge sites in amorphous materials, the resulting crystalline Ni0.85Se@amorphous NiFe hydroxide catalysts, featuring edge-enriched Ni0.85Se domains and mismatched crystalline–amorphous heterointerfaces, deliver exceptional OER activity with an ultralow overpotential of 225 mV at 10 mA cm–2, surpassing most state-of-the-art NiFe-based catalysts. Spectroscopic techniques and theoretical calculations reveal that the crystalline Ni0.85Se outer layer modulates the d-band center of Ni/Fe active sites, enhances charge transfer kinetics, and optimizes oxygen intermediate adsorption, thereby accelerating the OER process. Furthermore, in the anion exchange membrane water electrolyzer (AEMWE), standout performance with an ultralow cell voltage of 1.78 V at a current density of 1.0 A cm–2 is achieved. This work establishes a universal blueprint for integrating atomic-level structural design with interfacial engineering to unlock high-performance c-a heterocatalysts for energy conversion technologies.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"48 1","pages":""},"PeriodicalIF":17.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Manufacturing mRNA-Loaded Lipid Nanoparticles with Precise Size and Morphology Control 制造装载mrna的脂质纳米颗粒具有精确的尺寸和形态控制

IF 17.1 1区材料科学

ACS Nano Pub Date : 2025-09-15 DOI: 10.1021/acsnano.5c09800

Cedric Devos, Aniket Udepurkar, Peter Sagmeister, Ariana S. Hodlewsky, Julie Chen, Andrew Hatas, Nicole Ostrovsky, Mushriq Al-Jazrawe, Joy I. Ren, Andy Y. Liu, Richard D. Braatz, Allan S. Myerson

{"title":"Manufacturing mRNA-Loaded Lipid Nanoparticles with Precise Size and Morphology Control","authors":"Cedric Devos, Aniket Udepurkar, Peter Sagmeister, Ariana S. Hodlewsky, Julie Chen, Andrew Hatas, Nicole Ostrovsky, Mushriq Al-Jazrawe, Joy I. Ren, Andy Y. Liu, Richard D. Braatz, Allan S. Myerson","doi":"10.1021/acsnano.5c09800","DOIUrl":"https://doi.org/10.1021/acsnano.5c09800","url":null,"abstract":"Lipid nanoparticles (LNPs) are the leading platform for delivering nucleic acid therapeutics, produced by rapidly mixing lipids in ethanol with nucleic acid cargo in an aqueous buffer. LNP production is often approached with a mixing-focused mindset that reduces the entire self-assembly process to a single step, obscuring the relationship between the process inputs and LNP properties. Here, we present a method for producing mRNA-loaded LNPs, with independent and predictive control over both the size and morphology and without compromising other quality attributes. By decoupling particle design from mixing and formulation changes, this method enables the rational engineering of LNPs with defined properties. The method leverages mixing under high fusogenicity conditions, achieved by modulating the solvent composition, followed by timed postinjection of an aqueous buffer to kinetically arrest LNPs at the desired properties. We demonstrate the method using benchmark LNP formulations in an impinging jet mixer, a state-of-the-art technology for LNP manufacturing. The resulting LNPs exhibit up to an 8-fold increase in in vitro transfection efficacy compared to those produced by the conventional method. In addition, the method facilitates quality control and supports predictive modeling and rational process translation.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"34 1","pages":""},"PeriodicalIF":17.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Wet and Wild: Adventurous Wetting Expeditions on Tailored Surfaces of Self-Assembled Monolayers 潮湿和野生：在自组装单层的定制表面上冒险的潮湿探险

IF 17.1 1区材料科学

ACS Nano Pub Date : 2025-09-15 DOI: 10.1021/acsnano.5c11161

Zhuoyuan Ma, Zhuohuan Guo, Dayang Wang

引用次数: 0

Revealing the Role of Actin Cytoskeleton in Herpes Simplex Virus Type 1–Endosome Membrane Fusion by Single-Virus Tracking 通过单病毒追踪揭示肌动蛋白细胞骨架在单纯疱疹病毒1型核内体膜融合中的作用

IF 17.1 1区材料科学

ACS Nano Pub Date : 2025-09-15 DOI: 10.1021/acsnano.5c09935

Lei Du, Ai-Xin Ma, Jia-Xuan Chen, Jing Li, Zhi-Gang Wang, Dai-Wen Pang

{"title":"Revealing the Role of Actin Cytoskeleton in Herpes Simplex Virus Type 1–Endosome Membrane Fusion by Single-Virus Tracking","authors":"Lei Du, Ai-Xin Ma, Jia-Xuan Chen, Jing Li, Zhi-Gang Wang, Dai-Wen Pang","doi":"10.1021/acsnano.5c09935","DOIUrl":"https://doi.org/10.1021/acsnano.5c09935","url":null,"abstract":"The actin cytoskeleton is critical for viral membrane fusion and subsequent release of internal components. However, the actin cytoskeleton’s specific role in viral membrane fusion is poorly understood due to its involvement in multiple infection steps and methodological limitations. Here, we achieved dual quantum dot (QD) labeling of both the envelope and capsid of herpes simplex virus type 1 (HSV-1) by combining the streptavidin–Strep-tag II system with a biotinylated phospholipid-incorporated viral membrane labeling strategy. QD-based single-virus tracking revealed that HSV-1 enters MDCK cells via actin-dependent endocytosis, followed by microtubule-mediated transport to the perinuclear region. Critically, actin assembly was dispensable for virus-endosome membrane fusion. And myosin IIB on the actin cytoskeleton provided the mechanical force required for this process. These findings directly demonstrate the role of the actin cytoskeleton in HSV-1 endocytic uptake and subsequent fusion with endosomal membranes. This study provides important insights into the HSV-1 infection mechanism and intracellular membrane fusion processes.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"24 1","pages":""},"PeriodicalIF":17.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hybrid Exosome-Liposome Nanoparticles for Dual Modulation of Neuroinflammation and Lipid Metabolism in Ischemic Stroke. 混合外泌体-脂质体纳米颗粒对缺血性卒中中神经炎症和脂质代谢的双重调节。

IF 17.1 1区材料科学

ACS Nano Pub Date : 2025-09-15 DOI: 10.1021/acsnano.5c11417

Xixiang Xie,Xing Zhou,Wan Chen,Xu Deng,Jiajun Jiang,Zhongqing Wen,Chunmei Chen,Xiaoyu Chen,Chunxia Chen

{"title":"Hybrid Exosome-Liposome Nanoparticles for Dual Modulation of Neuroinflammation and Lipid Metabolism in Ischemic Stroke.","authors":"Xixiang Xie,Xing Zhou,Wan Chen,Xu Deng,Jiajun Jiang,Zhongqing Wen,Chunmei Chen,Xiaoyu Chen,Chunxia Chen","doi":"10.1021/acsnano.5c11417","DOIUrl":"https://doi.org/10.1021/acsnano.5c11417","url":null,"abstract":"Ischemic stroke, often modeled by middle cerebral artery occlusion and reperfusion (MCAO/R), involves severe neuroinflammation and lipid metabolic dysregulation that exacerbate neuronal damage. To address these dual pathological processes, we engineered a hybrid nanoplatform (Exo-Lip) by fusing neural stem cell-derived exosomes (Exo) with liposomes loaded with Yulangsan polysaccharide (Lip). Exosomes provide blood-brain barrier (BBB) permeability and intrinsic anti-inflammatory activity, while liposomes confer antioxidant and immunoregulatory effects. The resulting Exo-Lip exhibited improved colloidal stability and synergistic therapeutic potential. In MCAO/R mice, Exo-Lip markedly attenuated neuroinflammation by decreasing TNF-α and IL-6 while upregulating IL-10 and TGF-β. It restored lipid metabolism, alleviated oxidative stress, and preserved membrane integrity. TTC staining revealed a reduced infarct volume, and behavioral testing confirmed the recovery of motor and cognitive functions. Histological analyses further demonstrated neuronal survival and structural preservation. Transcriptomic profiling revealed that Exo-Lip modulated gene networks associated with inflammation and lipid regulation, including activation of the AKT/Nrf2/HO-1 signaling pathway. Collectively, these findings suggest that Exo-Lip represents a multifunctional, biomimetic nanotherapeutic capable of targeting both inflammatory and metabolic pathways in ischemic stroke. This work highlights a precision nanomedicine strategy with translational potential for central nervous system disorders.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"63 1","pages":""},"PeriodicalIF":17.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Full-Ocean-Depth-Oriented Poly(oxime-urethane) Coating: Construction and Protective Mechanism for Integrated Antifouling and Anticorrosion. 面向全海洋深度的聚肟聚氨酯涂料：防污防腐蚀一体化的结构与防护机理。

IF 17.1 1区材料科学

ACS Nano Pub Date : 2025-09-15 DOI: 10.1021/acsnano.5c09595

Peng Zhang,Shu Tian,Ruiqi Li,Guangming Lu,Qunji Xue,Liping Wang

{"title":"Full-Ocean-Depth-Oriented Poly(oxime-urethane) Coating: Construction and Protective Mechanism for Integrated Antifouling and Anticorrosion.","authors":"Peng Zhang,Shu Tian,Ruiqi Li,Guangming Lu,Qunji Xue,Liping Wang","doi":"10.1021/acsnano.5c09595","DOIUrl":"https://doi.org/10.1021/acsnano.5c09595","url":null,"abstract":"Full-ocean-depth (FOD) environment, characterized by extreme pressure, salinity, and biological complexity, presents severe challenges for surface antifouling and anticorrosion. High-performance coatings capable of withstanding such coupled extreme conditions are urgently needed. Herein, an integrated antifouling/anticorrosion poly(oxime-urethane) (PUDF) coating with a tunable microphase-separated structure was developed by incorporating the intrinsically antifouling unit (2,5-diformylfuran dioxime, DFFD) and the reactive high-barrier nanosheets (carboxyl-functionalized graphene oxide GO-COOH). The coating showed excellent biointerface resistance, suppressing protein and bacterial biofilm adhesion by 98 and 99%, respectively, and achieving 100% bactericidal efficacy against marine bacteria. After 2 months of immersion at both shallow-sea (2 m, East China Sea) and deep-sea (7730 m, Philippine Sea) sites, no macrofouling organisms or deep-sea microbial adhesion were observed. Cross-linking GO-COOH within the PUDF matrix enhanced microphase separation and mechanical robustness, enabling exceptional resistance to coupled corrosion. Under a combined condition of 15 MPa, 3.5 wt % NaCl, and 106 cells mL-1 Pseudomonas aeruginosa, the coating exhibited impedance two orders of magnitude higher than pristine PUDF. Microbial community analysis and density functional theory (DFT) simulations further elucidated the disruption of purine biosynthesis/nucleotide metabolism antifouling and low-adsorption/high-barrier anticorrosion synergistic protection mechanisms. This study offers a theoretical and practical basis for designing integrated protection materials for FOD applications.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"45 1","pages":""},"PeriodicalIF":17.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biomimetic Nanoregulators Mediated Tyrosine Hydroxylase mRNA and Stimulator of Interferon Genes Antagonist Codelivery for Synergistic Therapy on Parkinson's Disease. 仿生纳米调节剂介导的酪氨酸羟化酶mRNA和干扰素基因拮抗剂共递送协同治疗帕金森病

IF 17.1 1区材料科学

ACS Nano Pub Date : 2025-09-15 DOI: 10.1021/acsnano.5c00694

Lizhi Yang,Shuo Li,Chao Hou,Yukang Zhang,Linggang Cheng,Zihua Wang,Wen He,Wei Zhang

{"title":"Biomimetic Nanoregulators Mediated Tyrosine Hydroxylase mRNA and Stimulator of Interferon Genes Antagonist Codelivery for Synergistic Therapy on Parkinson's Disease.","authors":"Lizhi Yang,Shuo Li,Chao Hou,Yukang Zhang,Linggang Cheng,Zihua Wang,Wen He,Wei Zhang","doi":"10.1021/acsnano.5c00694","DOIUrl":"https://doi.org/10.1021/acsnano.5c00694","url":null,"abstract":"Degeneration of dopaminergic neurons in substantia nigra and neuroinflammation caused by microglia is one of the basic pathological features of Parkinson's disease (PD). Currently, therapeutic strategies that enhance dopaminergic neuronal function while simultaneously mitigating neuroinflammation hold great promise but face significant challenges in clinical application. To address these challenges, we developed a neuron-derived exosome biomimetic multifunctional nanoregulator codelivered tyrosine hydroxylase (TH) mRNA and stimulator of interferon genes (STING) antagonist. This nanoregulator system simultaneously delivers TH mRNA to enhance dopaminergic neuronal function and activity while incorporating the STING antagonist H-151 to promote microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, effectively suppressing neuroinflammation. Both in vitro and in vivo studies demonstrate that via mRNA therapy can precisely target and regulate dopamine (DA) synthesis, and that combined anti-inflammatory treatment effectively enhances this effect, significantly alleviating motor dysfunction in PD mice. Our findings present an effective approach for the development of PD medications and the advanced delivery of mRNA nanomedicines. This innovative nanoregulator represents a promising therapeutic strategy for managing neuroinflammation and improving dopaminergic neuronal function in PD by merging mRNA-based gene therapy with neuroinflammation modulation, addressing DA deficiency at its root and overcoming the current treatment obstacles in PD.","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"36 1","pages":""},"PeriodicalIF":17.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145059048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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