Nano Today最新文献

{"title":"Graphene-based origami with bidirectional bending and folding","authors":"Jiwoo Kim ,&nbsp;Donghoon Moon ,&nbsp;Yoona Kim ,&nbsp;Jae Hwan Jeong ,&nbsp;Jaehyung Yu ,&nbsp;Jangyup Son ,&nbsp;Arend M. van der Zande ,&nbsp;Gwan-Hyoung Lee","doi":"10.1016/j.nantod.2025.102955","DOIUrl":"10.1016/j.nantod.2025.102955","url":null,"abstract":"<div><div>The precise fabrication and deformation of three-dimensional (3D) microstructures, such as origami and kirigami with folded features typically ranging from a few to several tens of micrometers, have gained significant interest owing to their versatility in advanced microfabrication processes. However, conventional approaches relying on flexible polymers or thin metals face limitations, such as unidirectional bending and poor spatial resolution in localized deformation. Here, we present a strategy to construct graphene-based origami structures by harnessing the mechanical properties of graphene and exploiting electron beam (e-beam)–induced deformation of graphene-polymer double layer. Poly(methyl methacrylate) (PMMA)/graphene bilayer films exhibit a significant shift in the neutral axis due to the high in-plane stiffness of graphene, enabling controlled bidirectional bending under selective e-beam irradiation. By sequential e-beam exposure on PMMA-based structures with spatially patterned graphene, we achieve complex 3D geometries, including flower- and crown-like motifs, as well as folding mechanisms such as chair-like pop-up designs and box-shaped enclosures. Furthermore, we demonstrate rotational motion in wheel-shaped structures, translating out-of-plane bending into in-plane rotation by the shortening effect. Our approach expands the design freedom and functional capabilities of microfabricated systems, offering a powerful platform for programmable, reconfigurable 3D architectures in microelectromechanical systems (MEMS), robotics, and soft materials.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102955"},"PeriodicalIF":10.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682141","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}

{"title":"Two-step screening of lipid-polymer nanoparticles for efficient mRNA vaccine delivery and cancer immunotherapy","authors":"Mengwen Huang ,&nbsp;Chuhao Wang ,&nbsp;Xiaojuan Wang ,&nbsp;Dandan Chen ,&nbsp;Jin Ling ,&nbsp;Yue Yu ,&nbsp;Miaomiao Zhang ,&nbsp;Yucai Wang ,&nbsp;Congfei Xu ,&nbsp;Song Shen ,&nbsp;Xianzhu Yang ,&nbsp;Xiaojiao Du ,&nbsp;Jun Wang","doi":"10.1016/j.nantod.2025.102943","DOIUrl":"10.1016/j.nantod.2025.102943","url":null,"abstract":"<div><div>Messenger RNA (mRNA) vaccine is undoubtedly a medical breakthrough in drug development, however, its clinical application remains limited by inefficient delivery to target tissues and cells. In this study, we proposed a two-step screening strategy to optimize in vivo mRNA delivery system. First, we used the clinically approved cationic lipid, ionizable lipid and amphiphilic polymer to construct an initial library of lipid-polymer particles (LPP) with 60 various formulations for in vivo evaluation of their transfection efficiencies. Based on the results, we further constructed another library of 15 formulations to screen more effective LPPs. Then, the optimized LPP was selected and proved to be capable of effectively delivering mRNA to antigen-presenting cells (APCs), activating immune effector cells to trigger Th1/Th2 immune response, and promoting the formation of antigen-specific immune memory T cells. More importantly, LPP loaded with mRNA vaccine exhibited potent antitumor effects in both B16F10-OVA tumor model and human papillomavirus (HPV)-related TC-1 tumor model, exhibited comparable therapeutic activity to that of lipid nanoparticles (LNP) following intravenous injection. This study provides an innovative paradigm for the development of efficient mRNA delivery systems with high efficacy, safety, and clinical translation potential.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102943"},"PeriodicalIF":10.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682142","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}

{"title":"Endogenous enzyme-activatable catalytic DNA nanodevice for cancer cell-selective piRNA imaging and regulation","authors":"Ke Qin,&nbsp;Jiayin Zhao,&nbsp;Fei Ma,&nbsp;Chun-yang Zhang","doi":"10.1016/j.nantod.2025.102950","DOIUrl":"10.1016/j.nantod.2025.102950","url":null,"abstract":"<div><div>As the newly identified epigenetic regulators, piwi-interacting RNAs (piRNAs) are garnering increasing attention due to their potential implications in tumorigenesis. However, cancer cell-selective detection and regulation of cancer-associated piRNAs remains a significant challenge because of their broad distribution in both malignant and normal cells. Herein, we develop an endogenous enzyme-activatable catalytic DNA nanodevice (EE-CDN) for cell-selective imaging and regulation of piRNA. The EE-CDN remains inert in normal cells, which minimizes nonspecific background signal and avoids unwanted side effects. The EE-CDN can be activated only in cancer cells to enable cell-specific piRNA recognition. By anchoring the sensing elements onto a tetrahedral DNA scaffold, the EE-CDN allows amplified detection of piRNA with accelerated kinetics via spatially confined catalytic DNA assembly. Taking advantage of single-molecule detection, the EE-CDN can achieve attomolar sensitivity, enabling accurate discrimination and molecular subtyping of breast cancer in both cellular models and clinical tissue specimens. Importantly, the EE-CDN can facilitate in vivo tracking of piRNA in living breast cancer cells and breast cancer-bearing mice with superior spatial specificity, and it can efficiently suppress tumor growth in cells and mice models via depletion of endogenous piRNA, offering a powerful platform for precise diagnosis of cancer and targeted therapy.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102950"},"PeriodicalIF":10.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145682133","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}

{"title":"PNA aptamer-based bioreceptors for cardiac biomarker (cTnI) detection: Insight into the structural and stability-related aspects","authors":"Francesco Basini ,&nbsp;Abdellah Hambli ,&nbsp;Subhankar Sahu ,&nbsp;Rupali Bagale ,&nbsp;Manova Santhosh Yesupatham ,&nbsp;Christophe Ritzenthaler ,&nbsp;David Montaigne ,&nbsp;Eloise Woitrain ,&nbsp;Henri Happy ,&nbsp;Rabah Boukherroub ,&nbsp;Wolfgang Knoll ,&nbsp;Sabine Szunerits ,&nbsp;Roberto Corradini","doi":"10.1016/j.nantod.2025.102957","DOIUrl":"10.1016/j.nantod.2025.102957","url":null,"abstract":"<div><div>Aptamers, nucleic acid molecules that fold into specific three-dimensional structures, have been extensively used in the biosensing field to accomplish sensitive and specific monitoring of a wide range of biomarkers. Peptide nucleic acid (PNA), in this context, can be considered as a potential next-generation scaffold for aptamer synthesis and biomarker sensing, owing to its high stability in comparison to DNA counterparts. In this work, we investigated the performance of a series of PNA aptamers for monitoring of a prominent cardiac biomarker, cardiac troponin I (cTnI), using surface plasmon resonance (SPR) and showed that PNA sequences shorter than those previously reported for DNA can exhibit picomolar affinity, provided the essential structural features are preserved. Two different immobilization strategies (covalent and non-covalent) are validated in parallel for PNAs. The stability of sensor response in the presence of endonucleases such as DNase I was investigated further, as their occurrence in blood, plasma, and serum hydrolyses phosphodiester bonds and could be a limiting factor for point-of-care (PoC) application of DNA aptamers. Owing to their unnatural backbone, PNAs exhibited higher stability against DNase I in comparison to their DNA aptamer counterpart. Additionally, molecular dynamics (MD) simulations of DNA and PNA aptamers revealed similarities in their secondary structures, as well as distinctions in their propensity to adopt compact conformations. Overall, our findings not only provided a comprehensive framework for PNA design, surface functionalization, and cTnI biomarker detection using PNA-based bio-recognition scaffolds but also substantiated the biostability of PNAs, suggesting their high relevance for future PoC diagnostic applications.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102957"},"PeriodicalIF":10.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734042","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}

{"title":"Gas therapy in combating antimicrobial resistance: Mechanisms, synergistic strategies, and clinical translation challenges","authors":"Hongyang Lu ,&nbsp;Wei He ,&nbsp;Jiayu Li ,&nbsp;Lingjun Zhang ,&nbsp;Buyun Zhou ,&nbsp;Qiang Zhou ,&nbsp;Xiaowen Hu ,&nbsp;Quazi T.H. Shubhra ,&nbsp;Xiaosong He ,&nbsp;Xiaojun Cai","doi":"10.1016/j.nantod.2025.102960","DOIUrl":"10.1016/j.nantod.2025.102960","url":null,"abstract":"<div><div>The escalating prevalence of antimicrobial resistance (AMR), largely driven by the misuse and overuse of antibiotics, underscores the urgent need to explore alternative non-antibiotic therapeutic strategies. Gas therapy (GT), which utilizes gaseous signaling molecules (GSMs) such as carbon monoxide (CO), nitric oxide (NO), hydrogen sulfide (H₂S), oxygen (O₂), and hydrogen (H₂), has emerged as a promising antimicrobial strategy. These GSMs possess several distinctive advantages, including rapid and unimpeded diffusion into bacterial cells and biofilms, diverse antimicrobial mechanisms—such as reactive species generation, metabolic interference, and immune modulation—and a minimal risk of inducing AMR. This review systematically elucidates the antibacterial and anti-biofilm mechanisms of GSMs, emphasizing their integration with advanced modalities such as photodynamic therapy (PDT), photothermal therapy (PTT), sonodynamic therapy (SDT), and chemodynamic therapy (CDT) to enhance efficacy. We focus on how these strategies enable the precise delivery and controlled release of GSMs, how the released gases synergistically enhance therapeutic efficacy, and how these therapeutic platforms exhibit strong potential in combating infections caused by MDR bacteria and biofilm-associated pathogens. Despite preclinical success, critical barriers—including gas toxicity risks, biofilm penetration limitations, and regulatory hurdles—impede clinical translation. We further discuss future directions, advocating for engineered gas-releasing biomaterials, multimodal synergistic platforms, and artificial intelligence-driven design to optimize therapeutic outcomes. By bridging microbiology, nanotechnology, and clinical practice, this work underscores the potential of GT to redefine infection management in the post-antibiotic era.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"67 ","pages":"Article 102960"},"PeriodicalIF":10.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786544","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}

{"title":"Spatially confined multivalent aptamers in the cavity of a DNA nanocage against bacterial superantigens infection","authors":"Mengxia Duan ,&nbsp;Man Ding ,&nbsp;Kuaile Wu ,&nbsp;Zhouping Wang ,&nbsp;Shijia Wu ,&nbsp;Nuo Duan","doi":"10.1016/j.nantod.2025.102899","DOIUrl":"10.1016/j.nantod.2025.102899","url":null,"abstract":"<div><div>Aptamers as single-strand oligonucleotides obtained through <em>in vitro</em> screening techniques exhibit significant application potential due to their high target specificity, strong binding affinity, and inherent inhibitory capabilities. However, the easy entanglement among single-strand aptamers and excessive flexibility remains a huge challenge for keep high binding capabilities and dispersed spatial positioning in practical applications. Herein, we rationally designed a DNA nanocage structure loaded with multiple neutralizing aptamers (DNC-Apt). The programmability and the spatial confinement effect of DNC enable multiple single-strand aptamers to be reasonably fixed in the ideal spatial positions and achieve enhanced structural stability. Taking the enterotoxin A and B (SEs) secreted by <em>Staphylococcus aureus</em> as model target, both molecular docking and the ELONA experiment confirmed that the neutralizing aptamers integrated by this strategy achieved binding to different antigenic epitopes on SEs rely on spatially dispersed positioning, and exhibited enhanced binding ability (∼ 6 fold). The PBMC cell proliferation experiment demonstrated that this strategy could mediate the binding of SEs to receptors, thereby reducing the proliferation of T cells and the release of pro-inflammatory factors. Furthermore, the application of DNC-Apt in mice significantly reduced the inflammatory response and tissue damage caused by SEs. In conclusion, our research provided a reference for enhancing the application ability of aptamers and offered new strategies for alleviating the toxicity of bacterial toxins.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"66 ","pages":"Article 102899"},"PeriodicalIF":10.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145047333","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}

{"title":"Non-invasive CRISPR/Cas9 nanocapsules specifically edit α-synuclein for effective Parkinson’s disease treatment","authors":"Qingshan Yang ,&nbsp;Yujing Sang ,&nbsp;Nan Geng ,&nbsp;Yang Liu ,&nbsp;Dongya Zhang ,&nbsp;Yan Zou ,&nbsp;Meng Zheng","doi":"10.1016/j.nantod.2025.102903","DOIUrl":"10.1016/j.nantod.2025.102903","url":null,"abstract":"<div><div>Parkinson’s disease (PD) is the most common movement disorders, affecting more than 1 % of the elderly population aged over 60 years old. Targeting the accumulation of the toxic protein α-synuclein (α-Syn) (<em>SNCA</em>) is a common therapeutic strategy for PD. CRISPR/Cas9 gene technology could provide an avenue to achieve reduced levels of this protein. However, the lack of effective and safe brain delivery vectors greatly hampers its applications for brain disorders. In this paper, we developed glucose directed single-particle nanocapsules that efficiently delivers CRISPR/Cas9 into targeted brain lesions to specifically edit the <em>SNCA</em> gene. Our CRISPR/Cas9 nanocapsules have a small size of 32 nm and formed with a polymeric shell which protects Cas9/sgRNA from enzymatic degradation. Benefitting from surface glucose decoration, our nanocapsules exhibited blood brain barrier (BBB) permeability and accumulation in brain lesions after intravenous administration. Additionally, CRISPR/Cas9 nanocapsules selectively reduced expression of the <em>SNCA</em> leading to down regulation of α-Syn protein, M1/M2 microglial re-polarization, amelioration of neuroinflammation and recovery of tryptophan hydroxylase (TH) in A53T transgenic mice. Importantly, CRISPR/Cas9 nanocapsules significantly improved performance of mice in a variety behavioral test with negligible side effects. Therefore, the CRISPR/Cas9 nanocapsules provides a versatile but potent platform for genetic engineering in brain disorders, especially genome mutations relevant to neuronal disease.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"66 ","pages":"Article 102903"},"PeriodicalIF":10.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145217729","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}

{"title":"Polyelectrolyte nanocomplexes responsive to pathological neuronal discharge realize precise drug delivery for treating acute epilepsy via neurotransmitter homeostasis modulation","authors":"Xinrui Zhao ,&nbsp;Rong Yang ,&nbsp;Yage Sun ,&nbsp;Wenguang Liu","doi":"10.1016/j.nantod.2025.102916","DOIUrl":"10.1016/j.nantod.2025.102916","url":null,"abstract":"<div><div>Abnormal neuronal discharge due to disordered neurotransmitter homeostasis and harsh inflammation in epileptic focus is prone to cause recurrent seizures. However, current difficulties in drug delivery across blood-brain barrier (BBB) and regulation of complex pathological microenvironment hinder complete control of epilepsy with clinical therapies. Herein, a novel microenvironment-responsive drug-loaded polyelectrolyte nanocomplex (HCT-Fu@VB₆) formed by electrostatic self-assembly between tryptophan-modified hydroxypropyl chitosan (HCT) and fucoidan (Fu) with efficient vitamin B₆ (VB₆) loading, is developed for potent epilepsy treating, innovatively aiming to modulate neurotransmitters balance and attenuate the neuroinflammatory responses. Specifically, HCT confers the nanoparticles with specific binding affinity towards L-type amino acid transporter 1 expressed on brain endothelial cells, thereby significantly contributing to enhanced trans-BBB drug delivery efficiency. The fucoidan-containing polyelectrolyte nanocomplexes serve to provide intrinsic antioxidant property. Notably, the prepared polyelectrolyte nanocomplexes are dissociated in response to the mimic pathological neuronal discharges due to disturbed electrostatic equilibrium, facilitating accelerated VB₆ release for enhanced oxidative stress mitigation and effective neurotransmitter homeostasis modulation, acting as a competitive antagonist of ATP-gated purinergic P2RX7. The developed HCT-Fu@VB₆ nanoparticles demonstrate significant therapeutic efficacy as an electrically responsive trans-BBB drug delivery system, remarkably reducing seizure in epileptic rats while maintaining an excellent safety profile.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"66 ","pages":"Article 102916"},"PeriodicalIF":10.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145321238","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}

{"title":"Cancer models in nanomedicine research: Rethinking in vitro models for translational nanomedicine","authors":"Lucy Wang ,&nbsp;Oluwatomilayo Ejedenawe ,&nbsp;Stephanie Lheureux ,&nbsp;Danielle Rodin ,&nbsp;Christine Allen","doi":"10.1016/j.nantod.2025.102911","DOIUrl":"10.1016/j.nantod.2025.102911","url":null,"abstract":"<div><div>The U.S. FDA’s recent move to ease mandatory animal testing requirements has renewed scrutiny of in vitro models used in preclinical drug development. In nanomedicine, platforms such as spheroids, organoids, and organ-on-chip have advanced mechanistic modeling, yet the predictive validity of these systems remains limited by the biological relevance of the cell lines they incorporate. This Perspective critically evaluates the translational implications of using a narrow set of immortalized cancer cell lines in nanomedicine research – many of which lack genetic, phenotypic, or demographic alignment with cancer disease biology. Through a literature review of the 50 most cited studies in gynecologic cancer nanomedicine, we reveal an overreliance on just three cell lines in over 60–80 % of surveyed publications. We further show that most available gynecologic cancer cell lines are of European ancestry, with limited representation of global populations, despite growing evidence of population-specific differences in nanomedicine clinical efficacy and toxicity. These findings underscore a critical bottleneck in the development pipeline: the overuse of preclinical models that lack the biological variability necessary for robust clinical translation. As regulatory frameworks increasingly prioritize in vitro data in preclinical evaluation, the need to widen our cancer cell model repertoire becomes increasingly urgent. We propose actionable strategies to improve model representativeness and foster early stakeholder engagement in preclinical research. By embedding these practices into nanomedicine development, the field can strengthen translational outcomes, potentially reducing late-stage failures while better meeting the needs of the global oncology market.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"66 ","pages":"Article 102911"},"PeriodicalIF":10.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145321239","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}

{"title":"Silico-driven drug discovery: A paradigm shift for nanomedicine science and industry","authors":"Yadong Jin ,&nbsp;Yiting Zhou ,&nbsp;Zhuo Xu ,&nbsp;Zhifei Jin ,&nbsp;Huan Meng ,&nbsp;Suping Li ,&nbsp;Liang Yan ,&nbsp;Hui Wang ,&nbsp;Jia-Jia Zheng ,&nbsp;Xingfa Gao ,&nbsp;Yuliang Zhao","doi":"10.1016/j.nantod.2025.102918","DOIUrl":"10.1016/j.nantod.2025.102918","url":null,"abstract":"<div><div>The integration of artificial intelligence (AI) into drug discovery has evolved from early computer-aided design to advanced AI-driven methodologies, laying the foundation for a transformative paradigm: Silico-driven Drug Discovery (SDD). Unlike conventional approaches where AI supports isolated stages, SDD treats the entire research process, including literature understanding, hypothesis generation, molecular design, and experimental validation, as a unified, potentially autonomous system. This review proposes the THINK–BUILD–OPERATE (TBO) architecture as a universal framework for implementing SDD and outlines its six-level automation pathway from human-led to fully autonomous discovery. We highlight nanomedicine as an optimal frontier for SDD due to its well-defined theoretical foundations, abundant multi-omics and pharmacological data, and supportive regulatory shifts. By integrating domain-specific toolchains, large-scale AI models, and orchestrated self-driving laboratories, SDD can accelerate complex, multidisciplinary research while reducing costs and timelines. We further identify key challenges including AI model reliability, infrastructure interoperability, and automated laboratory versatility that must be addressed to achieve this vision. Ultimately, the convergence of AI, advanced laboratory automation, and global research networking holds the potential to transform drug discovery into an industrial-scale, programmable scientific enterprise.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"66 ","pages":"Article 102918"},"PeriodicalIF":10.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412556","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}