Dual-transformed CuO nanoparticles modulate plant nutrition and stress physiology in copper-starved plants.

Understanding bio-nano interactions and protein corona formation is critical for advancing nanomedicines towards clinical translation. However, conventional methods for nanoparticle analysis have limited utility for in situ analysis due to interference from unbound proteins present in bulk biological media. Electrical asymmetric flow field-flow fractionation (EAF4), which integrates AF4 with an applied electrical field, enables size and surface charge-based separation, and when coupled with online detectors, provides simultaneous measurement of particle size, electrophoretic mobility, and zeta potential, key parameters governing bio-nano interactions. Here, we report the first application of multiplexed EAF4 with online detection for evaluating biophysical changes occurring in polystyrene latex and silk nanoparticles, used as model nanomedicine systems, following exposure to serum under conditions that mimic the protein composition of cell culture media. Our findings reveal significant alterations in particle physical attributes, including particle size, shape factor, zeta potential, and electrophoretic mobility following exposure to protein-containing media. Furthermore, we demonstrate that EAF4 enables gentle fractionation of complex biological samples, providing comprehensive physicochemical profiling of diverse particulate and macromolecular species within nanoparticle-protein complexes. This work establishes EAF4 as a powerful analytical platform for resolving nano-bio interactions and guiding the rational design of next-generation nanomedicines.

Structure-corona-function engineering of micelles enables rapid hepatic bioactivation of clopidogrel for emergency antiplatelet therapy.

Liposomal nanocarriers in precision oncology: Advances and prospects.

Neuroinflammation plays an irreplaceable part in the pathogenesis and progression of Parkinson's disease (PD). While anti-inflammatory nanomedicine offers new hope for PD treatment, the nano-biological effects that govern their therapeutic outcomes remain largely unexplored. Herein, after investigating the mechanism of action of lentinan (LNT) on PD by network pharmacology, we report LNT and Mn3O4 integrated nanosystems (Mn3O4@LNT) as anti-neuroinflammatory agents for PD treatment. Proteomics analyses found that there are significant differences in protein corona composition between Mn3O4 and Mn3O4@LNT, and the protein coronas in Mn3O4@LNT are beneficial for BBB traversing and brian accumulation. In vivo and in vitro studies have shown that Mn3O4@LNT effectively alleviates the behavioral and pathological symptoms of PD by eliminating reactive oxygen species and reducing neuroinflammation. Transcriptomics further revealed the vital part of the phenotypic transformation of microglia and inflammatory response in the action of Mn3O4@LNT on the PD model. In summary, our study highlights the clinical application prospects of Mn3O4@LNT by benefiting the BBB traversing and promoting neuroinflammation mitigation in PD models.

With unique optical and physicochemical properties, carbon nanomaterials (CNMs), including carbon nanotubes, graphene-related materials, nanodiamonds, and carbon dots, are extensively explored as platforms for cancer diagnosis and treatment. However, in biofluids, CNMs spontaneously adsorb biomolecules to form an unpredictable corona, obstructing the implementation of their designed functions. In this review, we summarize how the intrinsic and acquired properties of CNMs affect protein corona formation, and the consequent biological and toxicological outcomes, as well as strategies to reshape the composition and structural organization of adsorbed proteins. This comprehensive knowledge will provide insights into developing CNMs with tailored corona and requested functions in cancer nanomedicine, advancing their translations into clinics.

With an aim to understand protein interactions of ultrasmall nanomaterials, this study investigates whether ultrasmall silver nanoclusters (AgNCs) interact with proteins differently from the classical protein corona observed for larger metal nanoparticles. To address this question, the interaction between glutathione-capped silver nanoclusters (GSH-AgNCs) and bovine serum albumin (BSA) is systematically investigated using a combination of ensemble-averaged and single-particle fluorescence techniques. AgNCs are synthesized and characterized, followed by investigation of their interaction with BSA using steady-state fluorescence spectroscopy, ζ-potential measurements, and isothermal titration calorimetry. These ensemble-averaged techniques have consistently revealed that the BSA-to-AgNCs binding stoichiometry remains below the threshold (BSA/AgNCs > 1) required for the formation of a stable protein corona, indicating a nanocluster-rich binding regime. Further insights are obtained from fluorescence correlation spectroscopy, which shows that the hydrodynamic radius of the BSA-AgNCs complex is significantly smaller than the thickness expected for a fully developed protein corona. This observation has provided direct physical evidence against complete protein shell formation. Additionally, circular dichroism and synchronous fluorescence measurements have further demonstrated that BSA retains its native secondary structure upon association with AgNCs. Overall, the results have depicted that ultrasmall AgNCs associate with proteins through complex formation instead of forming a protein corona. This mechanistic understanding is important for the rational design of AgNCs-based biosensing and biomedical applications.

Lactoferrin (Lf) is a multifunctional endogenous glycoprotein with well-established antimicrobial and immunomodulatory activities. In this work, we report a modular nanoparticle (NP) platform in which Lf is engineered as a multilayered protein corona onto immunomodulatory poly(lactic-co-glycolic acid) NPs (PLGA@Lf). By integrating the intrinsic anti-inflammatory properties of PLGA NPs with the diverse bioactivities of Lf, this hybrid corona design enables concurrent immune activation and suppression while enhancing antibacterial functionality. We demonstrate that Lf stably adsorbs onto PLGA NPs in a concentration-dependent manner, altering particle size and zeta potential consistent with multilayered corona formation. PLGA@Lf was shown to stimulate innate immune cells, enhancing Escherichia coli bioparticle phagocytosis, while simultaneously reducing pro-inflammatory cytokine levels in lipopolysaccharide (LPS)-challenged macrophages. Further antimicrobial activity studies demonstrated robust inhibition of bioluminescent E. coli activity in vitro. Lastly, in an in vivo therapeutic LPS-induced endotoxemia model, PLGA@Lf significantly reduced plasma levels of TNF-α compared to uncoated controls, highlighting their enhanced anti-inflammatory properties. Collectively, these results establish PLGA@Lf NPs as a dual-function nanomaterial platform that efficiently balances both immune stimulation and suppression responses, offering a promising strategy for managing infectious and inflammatory diseases.

Iron oxide (Fe3O4) nanoparticles (NPs) are widely utilized in water treatment, remediation, and biomedical applications. They are also identified as constituents of airborne particulate matter, heightening the risk of human exposure and potentially adversely affecting health. NPs inevitably form a protein corona in biological fluids, which redefines their identity and governs cellular interactions. Although the plasma protein corona has been extensively characterized, its intracellular fate following Fe3O4 uptake remains largely unresolved. During Fe3O4 extracellular-to-intracellular trafficking, protein coronas evolve dynamically across biological barriers; however, the remodeling, degradation, or retention of plasma proteins carried into cells by Fe3O4 remains unclear. In this study, we delineate the evolution of plasma-derived coronas from extracellular to intracellular environments. Proteomic analysis revealed that the initial plasma proteins were dynamically replaced by higher-affinity intracellular proteins upon Fe3O4 internalization. Furthermore, we emphasize the active role of the cell membrane in protein corona remodeling, with high-abundance fibrinogen being retained at the cell membrane through receptor regulation. These findings uncover a critical, previously overlooked dimension of protein-corona biology: the intracellular fate of plasma proteins dictates NPs' trafficking and toxicities, thereby linking environmental exposure to human health risk.

Protein corona fundamentally redefines the biological identity, cellular interactions, and in vivo fate of nanoparticles. Disease-induced alterations in blood composition generate pathological corona profiles; however, the impact of disease-mediated corona remodeling on the biological effects of nanoparticles remains poorly understood. Here, we systematically characterized the protein coronas and biological responses of surface-engineered polystyrene nanoparticles incubated with sera from healthy donors and patients with nonsmall cell lung cancer (NSCLC). Our findings show that disease status and nanoparticle surface chemistry jointly reprogram corona composition, leading to marked alterations in immune recognition and pharmacokinetic profiles. Specifically, NSCLC-derived coronas were enriched in complement proteins, resulting in pronounced complement activation and enhanced macrophage-mediated clearance, while attenuating systemic circulation of nanoparticles. These findings elucidate the critical role of disease-specific protein coronas in modulating nanobio interactions and underscore the necessity of accounting for pathological environments in the rational design and clinical translation of nanomedicines.

Advanced drug delivery systems have undergone rapid evolution to address limitations associated with conventional dosage forms, including poor bioavailability, non-specific distribution, and inadequate control over drug release. Increasing evidence indicates that biochemical and microbial environments play a decisive role in modulating delivery system performance and therapeutic outcomes. This review aims to critically analyze advanced drug delivery technologies through the lens of biochemical and microbial interactions, with emphasis on their influence on stability, targeting efficiency, controlled release, and clinical performance. A comprehensive evaluation of recent literature was conducted focusing on nanoparticle-based, polymeric, hydrogel, liposomal, biomimetic, and stimuli-responsive delivery platforms. Particular attention was given to protein corona formation, enzyme-mediated degradation, immune interactions, microbial biofilms, and microbiota-driven modulation of drug delivery behavior. Findings indicate that biochemical determinants such as protein adsorption, enzymatic activity, redox potential, and immune recognition significantly influence carrier biodistribution and release kinetics. Microbial factors, including gut microbiota and biofilm-forming pathogens, further affect drug stability, penetration, and efficacy. Advanced delivery platforms incorporating bio-responsive materials and biomimetic strategies demonstrate improved site-specific delivery, enhanced therapeutic outcomes in cancer and infectious diseases, and broader clinical applicability. Integration of biochemical and microbial insights into drug delivery design enhances therapeutic precision and translational potential. Future advancements are expected to rely on microbiome-aware, precision-driven, and smart bio-responsive systems to achieve improved clinical performance in modern pharmaceutics.

Under the influence of environmental pollution, chronic non-communicable diseases have increased. The epithelial lining of the airway forms the initial barrier; however, upon exposure, nanoplastics (NPs) may cross this interface and enter systemic circulation. This study aims to elucidate the effects of polypropylene nanoplastics (PP NPs) on the epithelial barrier and the interactions with serum proteins. PP beads were chemically degraded, characterized, and administered to the epithelial barrier-on-chip at a dose of 250 μg/mL, followed by continuous perfusion for 3 days. Their colloidal and biological behavior was investigated in cell culture medium supplemented with 10% fetal bovine serum. To explore clinical relevance, the interaction of PP NPs with human serum albumin was analyzed using molecular dynamics simulations, supported by protein profiling of plasma samples from healthy male and female individuals to understand gender-related differences. PP NPs with an average size of 305 nm were exposed to the epithelial barrier-on-chip leading to a decrease in cell viability via apoptotic cell death and transepithelial electrical resistance (TEER) value from ~2600 to 2200 Ω·cm2 with altered ZO-1 and ACE2 expression, as well as an increased proinflammatory response and intracellular reactive oxygen species (ROS) levels. [Correction added on 15 April 2026, after first online publication: The word "suppressed" has been deleted from the abstract.] The size of NPs increased to 364 nm after incubation with cell culture medium, indicating protein corona formation. The simulation revealed a biphasic adsorption pattern. The major differences in blood plasma of male and female donors were observed in the protein bands around 130 and 180 kDa. By integrating experimental and computational approaches, this study advances our understanding of how inhaled NPs may interact with blood proteins upon systemic exposure, with potential implications for human health risk assessment.

Protein corona (PC) often leads to immune recognition and accelerated clearance of nanomedicines. Cell membrane-coated nanoparticles (CM@NPs) have emerged as a biomimetic platform that enables prolonged circulation, immune evasion, and tissue targeting. However, the impact of PC formation on their hepatic fate remains underexplored. Here, we investigated how PC modulates hepatic clearance of CM@NPs. Magnetic silica nanoparticles were coated with red blood cell (RBC), macrophage (RAW264.7), or tumor cell (4T1) membranes to construct CM@NPs. Upon serum incubation, CM@NPs developed a PC that effectively masked key membrane ligands. Nano-flow cytometry analysis revealed that 87.7% of CD47 on RBC@NPs and 73.7% of CD44 on 4T1@NPs were masked by adsorbed proteins. In vivo biodistribution studies demonstrated a clearance shift from Kupffer cells to hepatocytes: hepatocyte uptake increased to 50.6%-57.7% for CM@NPs compared with 41.1% for uncoated NPs, while Kupffer uptake decreased from 52.2% to 34.5%-46.7%. Proteomic profiling identified apolipoprotein A1 enrichment on CM@NPs, favoring hepatocyte recognition, whereas complement C4b and immunoglobulin G dominated the corona on uncoated NPs, promoting immune-mediated clearance. These findings highlight the pivotal role of PC composition in modulating hepatic clearance pathways and provide mechanistic insights to guide rational design of CM@NPs for improved in vivo performance.

Modifying nanomedicines with targeting ligands represents an encouraging strategy for active tumor targeting, but its clinical failure underscores ongoing challenges. Herein, a series of liposomes with different targeting ligands (e.g., PEGylation, folic acid, mannose, RGD peptide, and melittin) were rationally designed to investigate the principles and mechanisms governing tumor targeting and penetration profiles. In primary and lung metastatic breast cancer models, these liposomes exhibited a systematic tendency of intratumor distribution, with melittin-modified liposomes showing optimal tumor targeting and therapeutic performance. Further studies revealed that the ligand modifications in liposomes could modulate the composition of their protein corona, particularly the level of Apolipoprotein A4 (ApoA4), which, in turn, influenced tumor targeting and intratumor distribution, ultimately affecting the therapeutic outcome of tumor inhibition and survival prolongation. This research provided a distinct correlation between ligand modification of liposomes and their in vivo biological performances, offering key insights for designing effective active-targeting nanomedicines.

Over the past decade, antibacterial materials have become a promising strategy to address both antibiotic-resistant and biomaterial-associated infections in clinical settings. Despite substantial progress, a gap remains between promising antibacterial performance in vitro and limited therapeutic outcomes in vivo. Herein, we present a mechanistic framework for understanding formulation-dependent antibacterial performance across five representative formulation architectures: nanoparticle-based systems, nanofibrous scaffolds, hydrogel matrices, surface coatings, and vesicular or microencapsulated carriers. We impart how structural organization and delivery dynamics regulate antibacterial mechanisms such as contact-mediated killing, controlled therapeutic release, and reactive oxygen species (ROS) generation and discuss their context-dependent suitability for diverse infection scenarios; these include acute wound infections, biofilm-associated implant infections, and chronic infected wounds. Particular emphasis is placed on factors contributing to the frequent failure of high in vitro log reduction efficacy translating into clinical success, including protein corona formation, biological barrier penetration, and dynamic host-pathogen interactions. Finally, we propose a comparative formulation-selection framework based on infection type, tissue environment, and therapeutic objectives to guide the rational design of next-generation antibacterial materials. This perspective bridges the gap between material innovation and clinical translation by highlighting formulation architecture as a central determinant of antibacterial performance in biomedical applications.

Time meets protein corona: the Vroman effect dictates macrophage recognition of PEGylated nanoparticles.

Nanoplastics (NPs) are emerging environmental pollutants with widespread human exposure and potential health risks. Once entering biological systems, NPs readily acquire a protein corona (PC) that governs their biological identity and toxicity. However, how disease-associated microenvironments reshape PC and modulate NPs toxicity remains poorly understood. Here, we investigated the effects of the oral inflammatory microenvironment on PC and the biological behavior of polystyrene (PS) NPs using periodontitis as a model disease. We identified a disease-specific PC formed in the saliva of periodontitis patients, characterized by enrichment of apolipoproteins, complement, and coagulation proteins. Compared with the normal PC, this disease-specific PC markedly enhanced macrophage uptake of PS NPs via increased phagocytosis and lipid raft/caveolin-mediated endocytosis, and triggered stronger pro-inflammatory responses, including elevated reactive oxygen species production, M1 macrophage polarization, and cytokine secretion. In vivo, oral exposure to PS NPs exacerbated alveolar bone loss and inflammation in a periodontitis mouse, accompanied by enhanced macrophage M1 polarization and systemic inflammatory responses. Mechanistically, these effects were closely associated with the complement-enriched disease-specific PC that amplified NPs-immune cell interactions. Overall, this study demonstrates that inflammatory microenvironments can reshape the PC of NPs and intensify their toxicological outcomes, underscoring the need for health-dependent risk assessment of NPs.

Cell recognition and uptake of extracellular vesicles (EVs) is mediated by a variety of surface molecules. Growing interest has recently been drawn towards glycan structures on EVs. Hyaluronic acid (HA) is a negatively charged glycosaminoglycan that can decorate the surface of EVs from different origins. HA is a ligand for adhesion receptor CD44, which is overexpressed in various cancers and inflammatory diseases. Although HA has been utilised as a surface decoration to improve CD44-mediated targeting of synthetic nanoparticles and EVs, the role of CD44 in the uptake of EVs is not well known. To assess the importance of CD44 in the interactions and endocytosis of HA-decorated EVs, uptake of HA-decorated and nondecorated EVs into CD44-expressing and -deficient cells was investigated using microscopic methods. The uptake of HA-decorated EVs was significantly increased into cells that expressed CD44, but no differences in endocytosis mechanisms were found. Additionally, the formation of plasma-derived protein corona in HA-decorated and nondecorated EVs was investigated using multi-parametric surface plasmon resonance and mass spectrometry. HA-decoration was found to cause a formation of thicker corona and enrichment of plasma-derived protein corona components. These findings highlight the role of HA in enhancing CD44-mediated EV targeting and modulating the composition of protein corona.

Systematic evaluation and hepatic targeting of a dual-fluorescence icaritin microemulsion: elucidating the protein corona-mediated delivery mechanism.

Protein corona-guided delivery of dextran-PLGA NPs for enhanced dendritic cell uptake, maturation and improved cancer immunotherapy.