搜索结果：Biomolecules & biomedicine

Electrostatic Force Microscopy (EFM), an extension of Atomic Force Microscopy (AFM), characterizes electrical properties at the nanoscale by detecting long range electrostatic force gradients. It enables simultaneous acquisition of topography and electrostatic information from biological samples. Dynamic electrical changes are fundamental across all life processes, from biomolecular charge transport to cellular electrophysiology. EFM's high resolution and nondestructive nature make it essential for revealing the physical mechanisms at biological interfaces. This review systematically elaborates the evolution of EFM principles, including optimized working modes tailored for biology, and analyzes its hierarchical applications, from biomolecules and subcellular structures to cells and pathological diagnosis. Cross scale dielectric correlations and current technical challenges are discussed, alongside advanced solutions such as heterodyne high harmonic detection and multimodal integration, offering a systematic perspective for EFM's translational development in biomedicine.

Once known only for its deadly effects, venom is now valued for its medicinal potential. The transformation of venomous substances into therapeutic agents, focusing on the synergy between natural toxins and drugs, is a recent topic of interest to the scientific community worldwide. Venom is a concoction of various biomolecules, including proteins, enzymes, peptides, protease inhibitors, and more. This review focuses on different categories of venomous species, their venom composition, the mechanism of venom deployment, and the pharmacokinetics. Besides this, it also focuses on the technological innovations while tracing venom's medical use from ancient practices to modern therapies. Additionally, it addresses the challenges and future directions, such as regulatory obstacles related to the approval processes for venom-derived drugs, illustrating the ongoing evolution from toxins to cure.

Carbon dots are quasi-spherical zero-dimensional nanomaterials. Small size and tunable optical properties render carbon dots with excellent biosensing ability. They exhibit fascinating excitation-wavelength-dependent emission properties, attributed to their sp2-carbon core. Presence of dopants alters the energy levels of carbon dots, improving their optical properties and their facile surface functionalization with suitable electron donor/acceptor groups or biomolecules results in modification of their electronic properties, which in turn facilitates fluorescence-based detection of significant biomarkers. Biocompatibility and hydrophilicity, along with their captivating optical properties, inspired researchers worldwide to utilize carbon dots in the timely detection of diabetes biomarkers. Diabetes has long been one of the more concerning diseases. It shows long-term adverse effects, harming vital organs like kidney, heart, eyes, etc. Therefore, it must be diagnosed at its inception stage. Impaired metabolism of insulin in diabetic patients elevate concentrations of several biomolecules like glucose, reactive oxygen species, etc., which can be detected by fluorescence. The widespread application of fluoresce sensing in biomedicine stems from its non-invasive nature and precision. This review article highlights the influence of doping and surface functionalization of carbon dots on their improved selectivity and biocompatibility toward biosensing of diabetes markers.

Molecularly imprinted technology （MIT） represents an advanced synthetic strategy that emulates biological recognition mechanisms， such as antigen-antibody or enzyme-substrate interactions， by creating three-dimensional cavity-like structures through the directional assembly of functional monomers around a template molecule. This process generates spatial and functional complementarity， enabling highly selective recognition of target species. Molecularly imprinted polymers （MIPs）， often described as "synthetic antibodies"， overcome the intrinsic limitations of natural biomolecules by offering superior selectivity， robustness， cost-effectiveness， and structural tunability. These features position MIPs as promising alternatives to natural antibodies in targeted sensing and drug delivery， with broad applications across biomedical， environmental， and pharmaceutical domains， including pollutant detection， and food safety monitoring. Despite substantial progress， key challenges remain， such as uneven imprinting layers， template residue， and limited aqueous compatibility in macromolecular imprinting. Furthermore， issues of industrial scalability， unclear recognition mechanisms， and insufficient integration with emerging fields such as microfluidics and artificial intelligence have hindered large-scale translation. In recent years， our research team has systematically advanced MIT through a tri-dimensional strategy encompassing high-throughput monomer screening， mechanistic elucidation of molecular recognition， and directional assembly of functional units. By establishing a standardized monomer library and integrating molecular dynamics simulations， we achieved precise material design under complex conditions. Through process optimization and material innovation， we developed a highly efficient solid-phase surface imprinting method that enables the fabrication of smart MIPs with stimuli-responsive properties （e.g.， temperature and pH）. These MIPs exhibit markedly enhanced binding affinity， with equilibrium dissociation constant （KD） reaching 10-12 mol/L， over four orders of magnitude higher than those of non-imprinted polymers （NIPs）. Building on these advances， we established cross-disciplinary application platforms， including affinity-based protein separation and purification systems capable of efficient dual-enzyme cascade immobilization and inactivated enzyme renaturation. In the biomedical domain， we developed ultrasensitive biosensing methods achieving picogram-level detection of heart failure biomarkers and single-digit （≈5 cells/mL） detection of cancer cells in whole blood， extending these methods toward integrated tumor theranostics and microbial community regulation. This paper comprehensively summarizes our team's recent innovations in the rational design， functionalized fabrication， and cross-disciplinary applications of MIPs， spanning biosensing， biocatalysis， and biomedical diagnostics/therapeutics， while contextualizing these within the latest global advances in biomedicine and catalysis. Looking forward， we identify three strategic research frontiers for next-generation MIT. （i） Smart responsive material systems： design MIPs capable of multi-stimuli responsiveness （e.g.， magnetic， photothermal， and pH cues） to enable programmable drug release， real-time signal monitoring， and dynamic feedback regulation. （ii） Quantitative modeling of dynamic recognition： establish multi-scale theoretical frameworks to elucidate coupling between cavity flexibility and target conformational dynamics， guiding structure optimization and function-oriented design of adaptive MIPs. （iii） Integrated intelligent theranostic platforms： integrate microfluidics and biomimetic recognition modules into closed-loop systems capable of biomarker detection， targeted delivery， and real-time therapeutic feedback， bridging the gap between in vitro sensing and in vivo precision intervention. Synergistic advancement along these trajectories will empower MIT to transcend its role as a "static recognition material" and evolve into an intelligent， adaptive， and systematic biomedical platform. Such evolution will accelerate the translation of MIT innovations from laboratory to clinic and industry， propelling progress in personalized medicine， point-of-care diagnostics， and synthetic biology， and yielding profound scientific and societal impact. 分子印迹技术（MIT）因设计灵活、适用广泛，已在疾病诊断、环境监测与食品安全等领域展现出重要应用潜力。然而，传统本体聚合法仍存在传质效率低、模板残留严重及大分子印迹效率不足等问题，同时受制于成本、标准化及跨学科融合等因素，限制了MIT的规模化应用。针对上述问题，本团队围绕功能单体的高通量筛选与识别机制解析，建立了标准化功能单体库，并结合粗粒化模拟，实现了复杂体系中印迹聚合物（MIPs）的精准设计与可控合成。通过技术路径优化与材料体系升级，开发出高效固相模板表面印迹及具温度/pH响应特性的智能印迹材料，其结合亲和力显著提升，平衡解离常数（K D）可达10-12 mol/L，较非印迹聚合物提升逾万倍。在应用层面，团队构建了MIPs的多维交叉体系：在生物分离纯化中实现复杂体系中蛋白质的高效富集；在生物催化中搭建双酶级联系统以提升催化效率与酶活复性；在生物医学方向开发出皮克（pg）级灵敏度的生物标志物检测与超低浓度肿瘤细胞（5个细胞/mL全血）识别平台，拓展至肿瘤诊疗一体化与微生物群落干预等前沿领域。本文综述了近5年MIT在生物医学与生物催化领域的研究进展，系统总结了本团队在MIPs理性设计、制备方法及交叉应用方面的成果，并展望其在智能响应材料与集成化诊疗系统中的发展方向。

The development of analytical approaches capable of detecting subtle protein conformational changes is of significant interest in biomedicine, particularly for disease diagnostics and biomolecular characterization. In this work, the tumor suppressor p53 protein was selected as a model system to evaluate an analytical platform based on Raman spectroscopy combined with surface-enhanced Raman spectroscopy (SERS) and supervised machine learning for the classification of closely related protein variants. Label-free Raman and SERS spectra of recombinant wild-type p53 and its hotspot mutants R175H and R273H were acquired on bare Al and Al coated with gold nanospheres, gold nanorods, and silver nanoparticles. Principal Component Analysis (PCA) revealed distinct spectral fingerprints among the p53 variants, with relevant contributions in the amide III and CH stretching regions, indicating subtle conformational differences. Supervised classification was performed using several machine learning algorithms under a nested, group-disjoint cross-validation protocol (holding out entire acquisition lines) to account for within-line spectral correlation. Among tested models, a linear Support Vector Machine (Linear-SVM) achieved the highest performance, reaching an accuracy of 92.9 ± 6.9% on AuNS@Al substrates. These results demonstrate that the integration of optimized nanostructured SERS substrates, Raman spectroscopy, and machine learning constitutes a robust analytical platform for the structural classification of wild-type and mutant p53 proteins. The proposed approach provides a versatile framework for studying conformational changes in biomolecules of biomedical relevance and supports its potential application in cancer biomarker detection and protein misfolding studies.

Bacterial Extracellular Vesicles (bEVs) are lipid (single- or double-bilayer) nanostructures secreted by virtually all bacteria that play fundamental roles in intercellular communication and have emerged as powerful, multifunctional tools in biomedicine. Their intrinsic ability to encapsulate and protect diverse biomolecules (including proteins, nucleic acids, lipids, metabolites and immunomodulatory factors) makes them highly attractive for therapeutic and diagnostic applications. Recent advances in molecular and synthetic biology have further expanded the biomedical potential of bEVs through targeted bioengineering strategies such as genetic manipulation, surface functionalisation, glycoengineering and modular display technologies, enabling the scalable production of customised bEVs with enhanced safety, stability, targeting precision and functional versatility. These innovations have unlocked a broad range of applications, including licenced and experimental vaccines, immune modulation strategies, drug delivery systems, diagnostic tools and regenerative medicine approaches. Despite this progress, key translational challenges remain, particularly regarding scalability, safety, standardisation and regulatory frameworks and addressing these issues will be critical for the successful integration of bEV-based technologies into novel therapeutic and diagnostic platforms.

Mannans are a major component of gymnosperm wood and are found in the seed of various non-leguminous plants. This group of polymers have received great attention because of their physico-chemical properties, such as their viscosity, polymerization, solubility, and gelling ability, as well as their biocompatibility, biodegradability, and non-toxicity. Mannans can be conjugated with different molecules, including drugs, carriers, and biomolecules such as proteins and antigens, in order to enhance the efficacy and potency of these molecules. Such conjugates are fabricated by methods such as reductive amination, aminoxyligation, carbodiimide coupling, mannosylation, and cyanylation. This review highlights different strategies for the synthesis of mannans, the various fabrication methods, and the wide applications of mannan conjugates in various fields such as tissue engineering, diagnostics, vaccine delivery, therapeutics, and biomedicine.

Carbon dots (CDs) have emerged as highly promising fluorescent nanomaterials due to their exceptional optical properties, biocompatibility, and facile synthesis. These attributes position them as versatile platforms for bioimaging, biosensing, and diagnostic applications in modern biomedicine. Significant progress has been achieved in translating CDs from proof-of-concept studies toward practical biomedical tools, particularly in real-time bioimaging and sensing. This review summarizes recent advancements in the synthesis and fluorescence mechanisms of CDs, with a focus on their applications as targeted fluorescent probes for critical analytes (e.g., metal ions, reactive oxygen species, enzymes, biomolecules) and cellular organelles. We provide a comparative analysis of CDs classification and correlate synthesis parameters with optical performance. Additionally, we critically evaluate the role of CDs in key disease areas, including oncology, cardiovascular disorders, neurodegenerative conditions, pulmonary and inflammatory diseases, highlighting their capacity for early diagnosis, therapeutic monitoring, and intraoperative guidance. Furthermore, we discuss the transition toward sustainable, green synthesis and the emerging role of computational tools, such as machine learning and artificial intelligence, in optimizing CDs properties and enhancing image interpretation. Despite their transformative potential, challenges persist in achieving synthesis reproducibility, enhancing selectivity via "turn-on" mechanisms, and validating long-term biocompatibility in vivo. Addressing these limitations through interdisciplinary collaboration and advanced engineering strategies is essential for fully realizing the clinical potential of CD-based fluorescent probes in modern medicine.

Nanophotonics, an interdisciplinary field merging nanotechnology and photonics, has enabled transformative advancements across diverse sectors, including green energy, biomedicine, and optical computing. This review comprehensively examines recent progress in nanophotonic principles and applications, highlighting key innovations in material design, device engineering, and system integration. In renewable energy, nanophotonics allows the use of light-trapping nanostructures and spectral control in perovskite solar cells, concentrating solar power systems, and thermophotovoltaics. This has significantly enhanced solar conversion efficiencies, approaching theoretical limits. In biosensing, nanophotonic platforms achieve unprecedented sensitivity in detecting biomolecules, pathogens, and pollutants, enabling real-time diagnostics and environmental monitoring. Medical applications leverage tailored light-matter interactions for precision photothermal therapy, image-guided surgery, and early disease detection. Furthermore, nanophotonics underpins next-generation optical neural networks and neuromorphic computing, offering ultrafast, energy-efficient alternatives to von Neumann architectures. Despite rapid growth, challenges in scalability, fabrication costs, and material stability persist. Future advancements will rely on novel materials, AI-driven design optimization, and multidisciplinary approaches to enable scalable, low-cost deployment. This review summarizes recent progress and highlights future trends, including novel material systems, multidisciplinary approaches, and enhanced computational capabilities, paving the way for transformative applications in this rapidly evolving field.

The resistance to antibiotics and the appearance of super-resistant bacteria have become a serious public health problem all around the world. Antibiotics repositioning through the development of metal-antibiotic complexes could be a solution because they improve antibiotic therapeutic activity by increasing its electronic delocalization and lipophilic nature, easing its access into cells and improving interactions with biomolecules. An example of a commonly used antibiotic is levofloxacin (Levo), a third-generation quinolone which has been coordinated with different metal ions to enhance its antibacterial and anti-tumor properties. This work presents the synthesis, crystallography, and photophysical characterization of three coordination compounds based on Levo with Zn(II), Tb(III) and Eu(III), alongside their physicochemical properties under biological media. The most relevant result of this work is that Levo coordinates with Eu(III) and Tb(III) showing the so-called antenna effect through energy transfer from the drug as a ligand to the lanthanide ions in biological medium. This result opens new avenues for exploring its localization in cells and enabling future therapeutic applications in biomedicine, where the drug could act as an antenna ligand. Furthermore, experimental absorption and emission spectra were obtained, and Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TD-DFT) calculations were carried out to characterize their electronic and photophysical properties and confirm the sensitization of the lanthanide ions by the Levo drug.

In cellulo protein assemblies, spanning protein cages, filaments, crystals, and biomolecular condensates, provide cells with modular strategies to package, organize, and regulate biomolecules and biochemical reactions. Their genetic encodability, structural diversity, and tunable material properties have also made them attractive biomaterials, where in cellulo fabrication has underpinned their precise assembly and broad applicability. This review surveys major classes of natural and engineered assemblies fabricated in cellulo, with particular emphasis on how their structure, chemistry, and material state shape functions. We compare diverse cellular reactors and outline how intracellular milieu, post-translational modifications, and folding/assembly machinery influence assembly outcomes. Engineering strategies for modifying the assemblies are summarized and mapped onto broad applications across fundamental biology, biomedicine, and nonbiological fields. Lastly, we highlight existing opportunities for engineering and designing in cellulo protein assemblies. Through this review, we hope to give a comprehensive overview of this exciting and rapidly growing field and share our perspective on the possible future directions.

Metal nanoclusters (MNCs), with their atomically precise structures and unique optical, electronic, and catalytic properties, have emerged as a new frontier in materials chemistry for applications in sensing, imaging, catalysis, optoelectronics, and biomedicine. However, their practical use is often limited by instability, low quantum yield, and aggregation, underscoring the need for deliberate engineering to unlock their full potential. Recent advances demonstrate that post-synthetic and in situ engineering strategies enable precise modulation of nanocluster composition, surface chemistry, and interfacial interactions, often leading to the formation of nanohybrid systems through integration of MNCs with polymers, biomolecules, carbon materials, and porous frameworks. These approaches regulate electronic structure, introduce new energy states, and suppress nonradiative pathways, thereby enhancing stability, photoluminescence, and multifunctionality. This review highlights these engineering strategies and discusses their role in advancing applications, particularly in sensing.

Biomolecular condensates are membrane-less organelles formed via liquid-liquid phase separation (LLPS) in cells, which play crucial roles in organizing biochemical reactions, regulating gene expression, and responding to environmental stimuli. These dynamic membrane-less organelles, such as stress granules and nucleoli, could concentrate specific proteins and nucleic acids for spatiotemporally controlling cellular processes. The engineering of synthetic condensates is beneficial for understanding condensates formation, simulating cellular behavior, and exploration of biological pathologies. Nucleic acid, as an important component of biomolecular condensates in cells, offers a unique platform to engineer synthetic condensates due to its programmability and precise and predictable Watson-Crick base pairing. The nucleic acid-based condensates were assembled through multivalent forces among nucleic acids or nucleic acid-peptide complexes. By designing and modifying nucleic acid sequences, the interaction forces could be regulated with external stimuli to control the formation and decomposition of nucleic acid-based condensates for various fields application. Our group has constructed various nucleic acid-based biomolecular condensates and applied them in biosensing and cellular regulation. We designed CUG repeats-based condensates for improving fluorescent RNA aptamer properties (enzymatic degradation resistance, thermal stability, photostability, and binding affinity to fluorophores) and detecting in vitro and intracellular biomolecules (adenosylmethionine and tetracycline), as well as target cells with overexpressed epithelial cell adhesion molecules. In addition, we leveraged the strong Watson-Crick base pairing ability to recruit the intracellular target RNA into condensates for cellular regulation. In this Account, we give an overview of nucleic acid-based biomolecular condensates. We first discuss the intermolecular interactions and forces involved in the formation of nucleic acid-based biomolecular condensates. Subsequently, we summarize recent research about nucleic acid-based condensates and their applications in the fields of biological imaging and biosensing, cell simulation, cellular regulation, and drug delivery. Finally, we outline the current challenges and future opportunities of nucleic acid-based biomolecular condensates. We hope that this Account will afford significant inspiration in the design of nucleic acid-based condensates and the applications in cell biology and biomedicines.

Silver nanoparticles (AgNPs) have attracted substantial scientific interest in biomedical research owing to their unique physicochemical characteristics, broad-spectrum antimicrobial activity, plasmonic properties, and therapeutic versatility. Although conventional physicochemical synthesis methods enable controlled NPs fabrication, their dependence on hazardous reagents, elevated energy input, and environmentally detrimental processing conditions has stimulated the development of sustainable biogenic alternatives. Biological synthesis utilizing plants, microorganisms, fungi, algae, and purified biomolecules has emerged as an eco-friendly and bio-compatible strategy for AgNP fabrication, enabling simultaneous reduction, stabilization, and intrinsic biofunctionalization of NPs. However, traditional biogenic synthesis remains constrained by limited mechanistic understanding, poor batch reproducibility, inadequate control over physicochemical properties, and challenges in large-scale manufacturing. Recent advances in bioengineering have transformed this field through the integration of metabolic engineering, synthetic biology, microfluidic-assisted synthesis, artificial intelligence-guided process optimization, and continuous-flow biomanufacturing, collectively enabling precision fabrication of biogenic AgNPs with enhanced uniformity, scalability, and functional tunability. Furthermore, strategic surface engineering and functionalization have expanded the applicability of biogenic AgNPs across targeted anticancer therapy, antimicrobial intervention, wound healing, regenerative medicine, drug delivery, and theranostic imaging. Despite these advancements, critical challenges remain regarding nano-bio interactions, toxicological safety, regulatory compliance, and translational scalability. Unlike conventional reviews focused primarily on green synthesis approaches, this review critically highlights emerging bioengineering paradigms that enable programmable, scalable, and precision-controlled biogenic AgNP fabrication. This review comprehensively examines next-generation paradigms and strategies for AgNPs biosynthesis, elucidates the molecular mechanisms governing their formation, highlights emerging functionalization and biomedical application paradigms, and discusses current translational barriers. Forming biogenic composites of AgNPs and heteroatom doped carbon nanodots needs intense research in near future.

Polydopamine (PDA), a mussel-inspired functional polymer, has become a key material for sensors and biomedical systems due to its exceptional adhesion, redox activity, and versatile surface chemistry. Unlike existing reviews that often treat PDA's fundamental chemistry and specific medical uses separately; this article addresses a critical gap by directly bridging PDA's structural properties to its practical performance in advanced technologies. Advances in controlled PDA polymerization have enabled the design of tailored nanostructures such as nanoparticles, hollow nanocapsules, thin films, and hybrid coatings that enhance performance across multiple biomedical platforms. In sensing and biosensing, PDA facilitates efficient biomolecule immobilization, improves electron transfer, and enables selective detection of biomarkers, making it highly effective for electrochemical, optical, and wearable sensor devices. In biomedicine, PDA's biocompatibility, photothermal properties, and ease of functionalization support a wide range of applications, including targeted drug delivery, multimodal cancer therapy, photothermal-chemotherapy combinations, tissue engineering scaffolds, wound healing materials, and controlled-release systems. By integrating recent progress in PDA structure, synthesis, and functionalization strategies, this review provides a comprehensive and application-oriented perspective on the expanding role of PDA in sensing technology and advanced biomedical engineering.

Nuclear transport is a vital system that mediates movement of essential biomolecules between the nucleus and cytoplasm. It is tightly regulated by the Importin (IMP) superfamily to maintain separation of cellular compartments. Cellular stress in various forms, particularly oxidative, can suspend nuclear transport and lead to cell death. Prolonged oxidative stress manifests in myriad conditions, including cancer, viral infection and metabolic disease. An IMP protein, Importin-13 (IMP13), retains function under stress, while all other IMP family members tested to date do not. Phylogenetic and structural analysis revealed Transportin-3 (TNPO3) as the closest homologue of IMP13, suggesting it may also retain its function under stress. Subcellular localisation studies indicated that TNPO3 maintained its typical subcellular localisation, even in the presence of stress, unlike most IMP family members. Also, fluorescence recovery after photobleaching (FRAP) demonstrated that TNPO3 shuttling is unaffected under stress. Co-immunoprecipitation studies examining cargo binding revealed the capacity of TNPO3 to bind its cargo in the presence of stress. This demonstrated for the first time that TNPO3 retains functionality under stress conditions, in contrast to other IMPs, but similar to IMP13. Furthermore, both IMP13 and TNPO3 appear to protect against the potentially critical mislocalisation of Ran, a key molecule involved in the maintenance of the nuclear transport system.

Quantum dots (QDs), a remarkable inorganic semiconductor nanocrystal capable of converting light energy into electrical, chemical, thermal, and other forms of energy, can be used to create super living systems through their fusion with cells, which hold tremendous potential for biomedical applications. Although considerable efforts have been devoted to delivering in vitro synthesized QDs into cells via endocytosis or electroporation, these approaches often suffer from poor biocompatibility, uncontrolled uptake pathways, and nonspecific intracellular interactions. Moreover, to satisfy the stringent demands of biological environments, QDs produced through conventional synthetic routes typically require extensive postsynthetic treatments, such as phase transfer into aqueous media and surface functionalization, which can irreversibly disrupt their surface structure and substantially compromise their photoluminescence quantum yield and photostability. Consequently, the exceptional optical properties of QDs are difficult to fully maintain when applied in physiological environments. Live-cell synthesis of QDs provides an innovative strategy to overcome these intrinsic limitations. By harnessing the intracellular spatiotemporally organized biochemical metabolic networks, this strategy enables the controlled synthesis of QDs while synchronously accomplishing in situ labeling. The resulting QDs are naturally coated with endogenous biomolecules and can be directed to form at specific subcellular locations, which inherently ensures high biocompatibility and precise integration with local cellular structures. This method establishes a robust foundation for in situ labeling of delicate cellular components and opens new avenues for high-fidelity acquisition of dynamic information within complex biological processes. Moreover, this flexible and universal strategy to fuse inorganic nanocrystals with live cells can endow organisms with enhanced or novel functionalities, holding significant promise for diverse applications in the fields of biomedicine and energy conversion. In this Account, we systematically summarize our efforts in the field of the live-cell synthesis of QDs. Our discussion encompasses the development of the "space-time-coupled" synthetic strategy, the elucidation of the key molecular mechanisms underlying the intracellular synthesis of QDs, and the diverse applications of this technique in pathogen detection, microvesicle labeling, site-specific protein labeling, and in vivo tumor imaging. Furthermore, inspired by the live-cell synthetic pathways, we introduce a cell-free "quasi-biosynthesis" system that enables controllable synthesis of near-infrared Ag2Se QDs and supports surface-chemistry-based strategies for precise modulation of photoluminescence properties. Finally, we outline the key challenges and future opportunities in this field, emphasizing that the synergistic integration of genetic engineering with precision materials science will profoundly advance the intracellular synthesis of nanocrystals and unlock new possibilities in high-precision sensing, dynamic regulation, and functional augmentation of biological systems. We believe that, with a deepened understanding of the synthetic mechanisms and continued innovation in synthetic methods, the spatial precision, operational reliability, and functional integration of QDs within living systems will be significantly enhanced, thereby providing a powerful toolkit for revealing biological mechanisms and advancing precise disease diagnosis and treatment strategies.

High-parameter tissue imaging enables detailed molecular analysis of single cells within their spatial environment. A current challenge to more complete tissue and single-cell spatial profiling is in situ data alignment across imaging platforms that quantify multiple types of biomolecules at differing resolutions. Here, we describe MIAAIM (Multi-omics Image Alignment and Analysis by Information Manifolds), a modular framework to align and process data from separate imaging technologies with distinct imaging resolutions and data complexity. MIAAIM is designed to be applied to align and analyze images of clinical biopsies from histological staining, imaging mass cytometry, and mass spectrometry imaging. A key advantage of the MIAAIM approach is its capacity to identify unbiased molecular phenotypes that correlate with cell identities and states determined using high-resolution targeted immunodetection. In a large diabetic foot ulcer (DFU) biopsy, this strategy allowed the identification of unique molecular characteristics of infiltrating immune cells as a function of local tissue health. In multi-core tissue microarrays (TMAs) of prostate cancer, MIAAIM allowed the classification of adjacent tumor grades with high accuracy, with over 90% of classification signal sourced from spatial features, generated from segmented cells across multiple imaging modalities while revealing novel cell/ immune signatures of the disease state. MIAAIM provides a disease and cell type agnostic general framework to construct multimodal tissue imaging datasets, yielding novel insights into the association of molecular analytes with cell subsets and their activation states for the analysis of complex tissue states.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by complex immune cell associations and continuous joint damage. Personalized clinical assessment and treatment options for RA remain hindered by a precision gap due to an inability to precisely match current global treatment strategies to individual molecular and spatial disease profiles. Recent advances in spatial transcriptomics and proteomics offer unprecedented opportunities to map molecular heterogeneity and spatial heterogeneity within RA tissues by identifying immune microenvironments activated during the disease, thus enabling precise therapeutic targeting. These techniques address the precision gap in RA by identifying distinct pathogenic subpopulations and cellular niches, providing insights into the biomolecules that possess significant therapeutic responses and are involved in disease progression. This review synthesizes recent findings demonstrating how spatial omics technologies, including spatial transcriptomics and proteomics, together with artificial intelligence, are transforming precision rheumatology.