Dental enamel cannot regenerate after acid damage. Fluoride merely retards demineralisation without restoring enamel's hierarchical nanostructure. This review critically discusses recent biomimetic strategies for functional enamel regeneration and acid-erosion resistance. Literature on peptide-guided mineralisation, mineralising agents, and multifunctional hybrid coatings was reviewed, focusing on approaches that replicate natural amelogenesis. Self-assembling peptides (P11–4, amelogenin analogues P26/LRAP) serve as molecular scaffolds for oriented hydroxyapatite nucleation. Complementary advances—amorphous calcium phosphate (ACP) stabilisers, ion-releasing bioactive glass nanoparticles, and adhesive polymeric coatings (chitosan, polydopamine)—provide synergistic mineral reinforcement and durable surface protection. In situ and early clinical studies consistently show improved remineralisation under controlled conditions, though clinical evidence remains limited and heterogeneous in design, lesion models, and follow-up. These systems enhance microhardness recovery and subsurface mineral deposition relative to fluoride alone, but long-term clinical superiority is not yet established. Biomimetic peptide-mineral systems shift dentistry from passive protection toward active tissue regeneration. AI-designed peptides combined with pH-responsive smart coatings hold strong promise for clinically sustainable, minimally invasive enamel protection.
Background: Fungal infections affect over 500 million people annually, with bacterial vaginosis accounting for 29%. Candida recurrence occurs in 9% of women, and azole resistance is rising, while biofilms and pH imbalance hinder therapy. This study developed tioconazole (TCZ)-loaded PLGA microparticles integrated into a microneedle array patch (MAP) for sustained transdermal delivery against fungal infections. Methods: TCZ-PLGA microparticles were optimized using Box–Behnken design and characterized for size, PDI, entrapment efficiency, and zeta potential, with XRD, DSC, and SEM analyses. The optimized formulation was integrated into a MAP, followed by ex vivo diffusion, in vitro release, skin irritation, and pharmacokinetic evaluations. Results: The optimized formulation (Batch B9) exhibited a particle size of 516.11 ± 1.15 nm, a narrow size distribution of 0.272 ± 0.18, a high entrapment efficiency of （81.60 ± 0.52）%, and a zeta potential of （−7.4 ± 0.23）mV. Additionally, the amorphous transformation of TCZ within the PLGA carrier was disclosed by XRD and DSC studies. SEM analysis revealed that TCZ-PLGA particles exhibited a circular shape. The TCZ-PLGA microparticle-integrated MAP demonstrated no evidence of irritation to the skin in rats. It enhanced drug diffusion ex vivo (1.85-fold compared to pure tioconazole-loaded MAP) and achieved 90% drug release within 12 h. Pharmacokinetic analysis showed that the TCZ-PLGA microparticle-integrated MAP had a half-life of (3.0 ± 0.59) h and an AUC0-t of 33.30 ± 1.54 μg/mL·h, indicating a steady and controlled release profile. In contrast, pure tioconazole exhibited a short half. Conclusion: The TCZ-PLGA MAP significantly improved drug retention and bioavailability, offering a safe, long-acting strategy with enhanced therapeutic efficacy and patient compliance for fungal infection treatment.
Baicalein is a multi-target flavonoid with broad preclinical anticancer activity, but its clinical translation is limited by poor aqueous solubility, chemical instability, rapid metabolism, and low bioavailability, restricting sustained tumor exposure. Carbon nanodots (CDs) are ultrasmall, surface-tunable, intrinsically fluorescent nanoparticles investigated for drug delivery and theranostic applications. This narrative review integrates baicalein’s anticancer mechanisms, delivery barriers, and CD-based formulation strategies to establish mechanistically grounded design principles for baicalein–CDs systems. A structured search of PubMed and Google Scholar (1988–January 2026) was conducted using baicalein-, carbon nanodot-, and cancer-related keywords, followed by thematic synthesis and qualitative appraisal of nanomaterial characterization and experimental rigor. Baicalein–CDs systems can be developed through physical loading, covalent conjugation, or hybrid approaches. Their performance is influenced by nano–bio interface interactions, including π–π stacking, hydrogen bonding, electrostatic interactions, and protein corona formation, which affect stability, drug retention, release behavior, and cellular uptake. Existing studies demonstrate successful baicalein loading or conjugation and report promising in vitro anticancer-related effects. However, most evidence remains preliminary, with limited serum-stability evaluation, inconsistent benchmarking, inadequate quantification of drug association, and insufficient in vivo biodistribution and safety data. This review proposes a minimum translational framework emphasizing standardized physicochemical characterization, stability and release studies in biologically relevant media, and pharmacokinetic, biodistribution, and toxicity evaluations aligned with chemistry, manufacturing and controls (CMC) principles. Overall, baicalein–CDs represent a promising but early-stage nanomedicine platform requiring stronger mechanistic and translational validation.
Transdermal drug delivery systems (TDDS), as an important alternative to oral and injectable administration, offer significant advantages including non-invasive delivery, avoidance of first-pass metabolism, and the ability to achieve sustained drug release. However, the physicochemical properties of the skin impose multiple barriers and limitations on transdermal drug delivery, which has motivated extensive research efforts to overcome these bottlenecks. This review focuses on the fundamental principles of transdermal drug transport and summarizes major technological approaches, including passive diffusion systems, active enhancement strategies, microneedle-based delivery platforms, and nanocarrier systems. In addition, recent advances in the application of TDDS for the treatment of skin diseases, immune disorders, neurological diseases, and cardiovascular diseases are reviewed. Finally, key challenges and future perspectives toward intelligent, personalized, and multifunctional TDDS are discussed, with an emphasis on clinical translation issues such as interindividual variability in skin barrier function, formulation design, safety, and regulatory considerations, underscoring the potential of TDDS in modern medicine.
Bone defect repair remains a major challenge in clinical orthopedics. Current gold-standard therapies, such as autologous bone grafting, are constrained by limited donor availability, donor-site morbidity, and additional surgical trauma. In recent years, stem cell-derived exosomes have emerged as a promising cell-free therapeutic strategy for bone regeneration because of their low immunogenicity, high biological activity, and considerable engineering potential. This review systematically summarizes the key mechanisms by which exosomes participate in bone repair, with particular emphasis on their ability to deliver bioactive cargoes, including specific miRNAs and proteins, to dynamically regulate inflammation, angiogenesis, osteogenic differentiation, and bone remodeling during the healing process. We further discuss the molecular networks involved in these processes, including BMP/Smad, Wnt/beta-catenin, PI3K/Akt, and other signaling pathways. In addition, we examine engineering strategies designed to improve exosome retention, targeting, and controlled release, such as hydrogel encapsulation and loading into three-dimensional bioprinted scaffolds, which have shown potential to enhance bone regeneration in preclinical bone defect models. Beyond summarizing the synergistic roles of exosomes in osteogenesis, angiogenesis, and immunomodulation, this review critically analyzes the major barriers that currently limit clinical translation, including standardized production, quality control, in vivo targeting, dosage definition, biodistribution, and long-term safety. Finally, we highlight future directions involving intelligent responsive delivery systems, deeper mechanistic validation, and integrated translational strategies to advance exosome-based bone repair from experimental research toward controllable, reproducible, and clinically applicable regenerative therapies.
Carbon dots (CDs), an emerging class of fluorescent carbon nanomaterials, have garnered considerable attention owing to their excellent optical properties and favorable biocompatibility. Among the diverse precursors for CDs synthesis, natural product-derived carbon dots (NCDs) have assumed a prominent role in promoting green and sustainable approaches because of their low cost and environmental compatibility, and research interest in these materials has expanded markedly in recent years. Whether produced from natural product monomers, plant extracts, traditional Chinese medicinal materials, or their associated waste products, NCDs often retain or confer intrinsic biological activities, thereby obviating the need for secondary drug-loading processes that are typical of conventional nanomaterials. Leveraging their remarkable photostability, low cytotoxicity, and excellent biocompatibility, NCDs demonstrate broad application potential in diverse fields such as in vivo and in vitro imaging, ion detection, drug delivery, and disease therapy. This review systematically summarizes strategies for selecting NCD precursors, delineates the characteristics and common features of NCDs derived from various precursor classes, and discusses the rationale and methodologies for precursor doping to enable precise modulation of CDs performance. The review aims to provide theoretical guidance for the rational design and optimization of precursors and synthesis conditions to meet defined performance criteria.
Postoperative pancreatic fistula (POPF) represents the most prevalent and perilous complication following pancreatic resection, frequently precipitating severe infection, hemorrhage, and multiple organ dysfunction syndrome, thereby substantially increasing patient mortality and healthcare burden. Conventional surgical interventions and pharmacological therapies have inherent limitations in the prophylaxis and management of POPF and its secondary infectious sequelae. In recent years, biomaterials have emerged as innovative therapeutic modalities for this clinical challenge because of their engineerable physicochemical properties. This review aims to systematically elucidate recent advances in biomaterial-based strategies for POPF prevention and treatment, with particular emphasis on their dual mechanistic functions: (i) serving as physical barriers to achieve immediate sealing, adhesion, and mechanical support of the surgical site, thereby precluding pancreatic fluid extravasation; and (ii) actively modulating the local microenvironment through the incorporation of bioactive agents or intrinsic functionalization, exerting synergistic anti-infection, anti-inflammatory, and tissue regeneration and neovascularization effects. Furthermore, this article critically analyzes current challenges pertaining to biocompatibility, degradation controllability, and clinical translational efficiency while future design trajectories toward precision medicine-oriented and stimuli-responsive multifunctional biomaterials are prospected.
Cancer remains one of the most pressing global health challenges, with current treatments often limited by toxicity and poor targeting. Metal-based nanomaterials (MNMs) have emerged as promising candidates to overcome these limitations due to their unique catalytic, photothermal, and immunomodulatory properties. This review provides an overview of platinum-, iron-, manganese-, and copper-based MNMs, highlighting their mechanisms in cancer therapy. These include catalytic generation of reactive oxygen species (ROS), photothermal conversion, and immune activation, enabling multi-modal therapies such as photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), and immunotherapy. The review also discusses the challenges of translating MNMs into clinical practice, including biosafety concerns, pharmacokinetics, and scalability. Finally, future perspectives on the design of biodegradable, immune-integrated, and imaging-guided MNMs for personalized cancer treatment are proposed.
The present study aims to synthesized zinc oxide nanoparticles (ZnO NPs) in an sustainable approach by using gallic acid (GA) as a stabilising and bio-reductant. The synthesized GA-ZnO NPs were characterized by UV-Vis, FTIR, XRD, FE-SEM, and EDX, confirming their formation and structure. The nanoparticles demonstrated significant antimicrobial activity against both Gram-positive and Gram-negative bacteria, as well as the fungus C. albicans. The synthesized GA-ZnO NPs were confirmed by the UV-DRS spectrum, peak absorption exhibited at 320 nm is unique to ZnO NPs. FTIR data might prove that GA-ZnO NPs have phytochemical capping. The synthesized nanoparticles' average size was 33 nm based on the XRD pattern. The characterisation performed using a FE-SEM demonstrates the existence of GA-ZnO NPs in both hexagonal and spherical morphologies. The EDX data indicate the composition of Zinc (32 %) and Oxygen (63 %), exhibiting pronounced energy signatures accordingly. The antibacterial efficacy of ZnO-NPs demonstrated a maximal inhibition zone of (20.1 ± 0.48 mm) against C. albicans and (14 ± 0.66 mm) against S. aureus at a concentration of 100 μg/mL, respectively. Additionally, they exhibited strong antioxidant properties, with IC50 values of 282.5 µg/mL (DPPH assay) and 2.326 µg/mL (ABTS assay). The GA-ZnO NPs also showed notable cytotoxicity against cervical cancer (HeLa) cells, with an IC50 value of 34.71 µg/mL. Our study revealed that gallic acid exhibits broad-spectrum interaction with microbial and cancer cell targets, showing notable binding efficacy, especially against Staphylococcus aureus in comparison with other proteins. Toxicity profiling reveals it to be non-hepatotoxic, non-cytotoxic, and non-immunotoxic. These findings support its potential as a safe, moderately effective anticancer and antimicrobial agent.
Heart failure (HF) is a severe cardiovascular disease with high morbidity and mortality, creating an urgent need for rapid, accurate, and highly sensitive detection to support early diagnosis and disease assessment. Traditional diagnostic approaches, however, are limited in sensitivity, specificity, and accuracy, making early and reliable detection challenging. In this work, we developed a core-shell upconversion nanoprobe with a ratiometric optical readout for highly sensitive and specific detection of heart failure-related biomarkers. The platform exhibits ultrahigh sensitivity with a wide linear detection range from 10 pg mL−1 to 100 ng mL−1 and a low detection limit of 3.0 pg mL−1, providing stable and quantitative readouts. Leveraging antibody-mediated recognition, the nanoprobe ensures excellent target specificity. Moreover, it is successfully applied to cardiomyocyte imaging, demonstrating good biocompatibility and adaptability to the cellular environment. This study provides a practical strategy for efficient heart failure diagnosis and establishes a foundation for the broader use of upconversion nanoprobes in cardiovascular disease detection and bioimaging.
Exosomes, as cell-derived nanoscale vesicles, are characterized by their ability to selectively encapsulate and transfer biomolecules—including proteins, nucleic acids, and lipids—from their parental cells, thereby playing a pivotal role in intercellular communication and regulating various physiological and pathological processes. These vesicles exhibit distinct biological properties, such as excellent biocompatibility, multifaceted heterogeneity, and effective targeting. With the in-depth study of the biological properties of exosomes and their functions, strategies for their application in disease diagnosis and therapy have been expanding. This review offers a detailed overview of exosome biogenesis, isolation, and identification, elucidates the properties of exosomes and their impact on biological responses, and evaluates the current state of research on exosomes in disease diagnosis and treatment through clinical trials and published literature. We particularly highlight the application of exosomes as biomarkers for early screening and monitoring of refractory diseases, such as cancer and neurodegenerative disorders. Furthermore, we summarize the innovative applications of exosomes that are currently at the forefront of drug delivery, gene therapy, and regenerative medicine. The study also deeply analyzes the technical bottlenecks facing the clinical application of exosomes and proposes directions for future research. In conclusion, exosomes, as emerging molecules for disease diagnosis and treatment, hold significant clinical application prospects through multidisciplinary collaborative innovation.
Surface-enhanced Raman scattering (SERS) has evolved from a fundamental phenomenon to a powerful analytical technique, heavily reliant on the properties of the substrate. This review comprehensively summarizes recent advances in SERS substrates, with a specific focus on the pivotal role of dimensionality and size effects. We systematically discuss the characteristics and enhancement mechanisms of diverse nanomaterials. The emergence of metal single-atom materials as a new frontier, enabling exceptional charge transfer efficiency via local microenvironment engineering, is also highlighted. We elucidate how dimensional and size control tailor electromagnetic responses and chemical enhancement pathways, ultimately dictating SERS activity. Additionally, the review addresses prevailing challenges in substrate reproducibility, stability, and real-world application, while offering perspectives on future research directions. This work aims to deepen the understanding of size-dependent SERS effects and provide guidelines for designing highly sensitive substrates.
Single-cell is important target in bioelectrochemical analysis because essential life processes, such as the production, storage, and secretion of neurotransmitters and other key biomolecules, occur at the cellular and subcellular levels. Owing to the small cell volume, low intracellular analyte concentrations, rapid reaction kinetics, and the inherent fragility of living cells, efficient single-cell detection requires analytical techniques with high sensitivity, high spatiotemporal resolution, and minimal invasiveness. As an emerging approach, single-cell electrochemical analysis offers unique advantages in probing cellular heterogeneity and dynamic biological processes due to its excellent sensitivity and real-time monitoring capability. This review systematically summarizes recent advances in electrode based single-cell electrochemical analysis, with a focus on micro-nanoelectrode technologies, nanocapillaries, nanopores, nanopipette probes, and nanoscale electrochemical sensing platforms. Key fabrication strategies, including laser pulling, etching methods, and chemical vapor deposition, are discussed. In addition, representative applications of these techniques in the analysis of nucleic acids, neurotransmitters, and reactive oxygen and nitrogen species are reviewed. However, challenges remain in areas such as micro-nanofabrication technologies and multi-analyte detection.
Lung adenocarcinoma (LUAD) remains one of the leading causes of cancer-related deaths globally, necessitating more effective diagnostic and prognostic biomarkers. This study aims to identify and validate a robust diagnostic signature for LUAD using machine learning algorithms and multi-cohort analysis. We performed differential expression analysis on two LUAD datasets (GSE32863 and GSE116959) and intersected differentially expressed genes with the Wnt signaling pathway gene set to identify 10 hub genes. LASSO regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms were employed to screen for candidate biomarkers. TMEM132A and CDH3 were identified as independent diagnostic indicators through multivariate logistic regression analysis. A diagnostic model based on these two genes achieved an area under the receiver operating characteristic curve (AUC) of 0.988 (95 % confidence interval: 0.968–1.000) in the training cohort and consistent performance across nine independent validation datasets (AUC range: 0.870–0.979). A nomogram was constructed to integrate the RiskScore with clinical variables, which significantly improved diagnostic accuracy compared to clinical variables alone. The model demonstrated exceptional early diagnostic potential for Stage I LUAD (AUC: 0.999). The expression of TMEM132A and CDH3 was validated at the protein and mRNA levels by immunohistochemistry and qRT-PCR, respectively. Immune infiltration analysis revealed that the diagnostic signature correlates with distinct tumor microenvironment profiles, including alterations in Th2 cells, mast cells, and dendritic cells. These findings establish a robust and practical diagnostic model with strong potential for clinical application in LUAD diagnosis and patient stratification.
Piezoelectric nanocellulose derivatives combine the electromechanical properties of cellulose nanocrystals with chemically compatible functionalization and nanocomposite fabrication approaches, aiming to design biocompatible, mechanically similar cartilage monitors. Focusing on scalable, clinically relevant objects, this review assesses design choices, fabrication methods, and translation challenges. It covers surface derivatisation, polymer matrix reinforcement, and alignment techniques achieved through electrospinning, 3D printing, thin-film deposition, and scaffold integration with microelectronics, using standardised mechanical loading protocols. Mechanical piezoelectric nanocellulose biosensors offer real-time, minimally invasive, tissue-matched mechano-electrical signals to predict early cartilage degeneration, facilitate earlier diagnosis, enable personalised closed-loop rehabilitation, support self-powered telemetry, and streamline clinical translation. Enhanced responses are observed in oriented nanofibers, conductive or piezo-enhancing matrices, and specific surface chemistries, resulting in prototype sensors capable of measuring physiological cartilage pressures and strains with desirable signal-to-noise ratios in benchtop models, with potential for wireless telemetry with low power consumption. Major challenges include achieving consistent large-scale orientation under synovial conditions, ensuring long-term performance in vivo, and enabling reproducible wireless readouts and encapsulations. In conclusion, piezoelectric nanocellulose offers a sustainable, promising pathway to next-generation, sensitive, and potentially self-powered cartilage sensors. Future research should focus on scalable production, in vivo validation, open data for reproducibility, interdisciplinary collaboration with clinicians, and establishing quantitative performance metrics. Progress in these areas holds the potential to accelerate the clinical application of diagnostic and rehabilitation devices.
To explore potential therapeutic strategies for triple-negative breast cancer (TNBC) and investigate targeted CDK9 inhibitors with reduced toxicity, a CRISPR/Cas9-based bionic tumor cell membrane-encapsulated nanocomposite was developed. The system primarily consists of mesoporous polydopamine, Cas9/gRNA, and the outer layer of TNBC cell membranes. It not only enables controlled release of Cas9/gRNA to suppress CDK9 expression but also synergistically induces apoptosis through photothermal effects. This nanocomposite exhibits excellent biocompatibility and demonstrates outstanding synergistic therapeutic effects. 808 nm irradiation triggers the release of Cas9/gRNA that inhibits CDK9, while simultaneously generating photothermal effects. This induces downregulation of Mcl-1 and cleavage of Caspase3, promoting tumor cell apoptosis, thereby achieving potent antitumor efficacy. This approach offers a promising strategy for targeting CDK9 in the treatment of triple-negative breast cancer.
Vaccines prevent infectious diseases by enhancing both innate and adaptive immune responses, while adjuvants amplify, accelerate, or prolong these responses, thereby increasing vaccine efficacy. This article reviews recent advancements in the use of nanomaterials as vaccine adjuvants. From traditional aluminum salts and complete Freund's adjuvants to modern Toll-like receptor (TLR), Stimulator of interferon genes (STING), composite, and nano adjuvants, the focus has increasingly shifted toward the precise control of immune responses. With the emergence of new technologies and design approaches, nanomaterials have made it feasible to develop adjuvants that are safe, easy to produce, industrially scalable, long-term stable, cost-effective, biodegradable, compatible with antigens, capable of sustained antigen release, and able to elicit the desired immune response.
Radiotherapy remains one of the cornerstone modalities in the clinical treatment of malignant tumors. However, the intrinsic radioresistance of tumor cells—particularly hypoxia-induced tolerance within the tumor microenvironment—significantly limits therapeutic efficacy. With advancements in nanomedicine, high-atomic-number (high-Z) heavy metal-based nanoparticles (GNPs) have demonstrated great potential in overcoming tumor radioresistance due to their unique physical, chemical, and biological properties. This review systematically summarizes recent progress on high-Z metal-based nanoparticles (e.g., gold, gadolinium, bismuth, and iridium), their nanoscale metal–organic frameworks (nMOFs, e.g., hafnium-based and zirconium-based systems), and metal-doped nanomaterials developed for enhancing radiotherapy outcomes. We highlight the mechanisms by which these materials achieve radiosensitization, including enhancement of local radiation energy deposition, catalytic generation of reactive oxygen species (ROS), modulation of the tumor microenvironment, and activation of immunogenic cell death (ICD). The advantages of high-Z metal-based nMOFs in drug delivery and catalytic performance are also discussed. Finally, we analyze the major translational challenges, including biodistribution and long-term toxicity, and propose material engineering strategies and future research directions toward integrated theranostic applications.
Chimeric antigen receptor T cell therapy represents a transformative advancement in immunotherapy, wherein engineered T cells target tumor antigens, achieving high response rates in hematological malignancies. Its therapeutic applications have further expanded to infectious diseases, autoimmune diseases, and fibrosis. However, Chimeric antigen receptor T cell therapy still faces major unresolved limitations: poor infiltration into solid tumors, off-target toxicity, suppression in B cell malignancies, drug resistance, immunosuppressive tumor microenvironment, high manufacturing costs of cell therapies, and insufficient long-term persistence. Lipid nanoparticles have emerged as a revolutionary tool for mRNA vaccines and gene therapy. As a non-viral delivery system, lipid nanoparticles enable precise nucleic acid delivery via their unique molecular design, efficient encapsulation capacity, targetability, biocompatibility, and scalable manufacturing. They have been successfully applied in mRNA vaccines, providing a versatile platform for gene therapy. In recent years, lipid nanoparticles have innovatively addressed current limitations of immune cell therapies and expanded their therapeutic scope in ex vivo/in vivo mRNA-based chimeric antigen receptor engineering of immune cells by enabling modular, transient, and tissue-specific chimeric antigen receptor expression. This review systematically explores the cutting-edge advances in in vivo chimeric antigen receptor T cell engineering, highlights the advantages of Lipid nanoparticles over lentiviral vectors in terms of manufacturing processes, cytotoxicity, and safety, and discusses the application prospects and future directions of in vivo chimeric antigen receptor T cell engineering for disease treatment.
