We report the development of a sensitive biosensing platform based on a shear-horizontal surface acoustic wave (SH-SAW) device and paper fluidics, with the potential to be used outside centralized laboratory settings. Systematic research on the biorecognition surface, blocking agent, fluidics and measuring unit allowed us to transform a laboratory-based method into a field-deployable device. As a proof-of-concept, the platform was used for the detection of SARS-CoV-2 anti-spike antibodies on a surface-immobilized spike protein, tested in both simulated and human blood serum samples. A poly-L-lysine (PLL) layer was selected as a biocompatible surface for spike protein immobilization; the polymer layer can be easily removed through gentle mechanical rubbing, allowing regeneration and multiple uses of the sensing device. This surface, combined with novel paper-based capillary fluidics, enabled real-time monitoring of spike antibody binding via acoustic wave phase measurements in the range of 1-100 nM antibodies in 1% v/v serum. Further acoustic wave amplitude amplification and a tenfold improvement in the detection limit (0.1 nM) were achieved by the use of gold nanoparticles conjugated with a secondary antibody. This optimized assay was successfully evaluated in a small pilot clinical study of 20 patient samples. Our new SH-SAW immunosensor exhibited sensitivity and specificity comparable to commercial systems with standard fluidics and instrumentation; importantly, its limit of detection is better than the clinically relevant value of ∼11 RU mL-1. This portable, low-cost platform, combining a pocket-size network analyzer with disposable paper fluidics and a regenerable sensing surface, offers a promising solution for quantitative antibody detection near or at the point-of-care.

Recent evidence on resistance to immune checkpoint inhibitors (ICIs) has necessitated the exploration of alternative cancer therapies with increased treatment responsiveness among patients, especially for solid tumors. Phototherapy with red or near-infrared light is considered as one such potential approach, but it espouses limited efficacy in treating solid tumors and aggravates cancer progression in some instances. In contrast, genetically engineered T cells bearing chimeric antigen receptors (CAR) targeting tumor-specific neo-antigens have demonstrated significant therapeutic potential and have advanced into clinical trials. Several reports have annotated numerous neo-antigens, eventually enhancing CAR T-cell design and efficacy. Nevertheless, numerous clinical trials envisaged 'hyperimmune response' as a limitation of effective CAR T treatment for cold tumors, driving the development of CAR engineered macrophages (CAR M) and natural killer (CAR NK) cells which efficiently infiltrated cold tumors and elicited better treatment response. CAR NK therapy is advantageous for its MHC independent cytotoxicity which prevents cytokine storm along with graft versus host disease (GVHD). However, isolation, gene manipulation and proliferation of the immune cells from patients is not time efficient. Involving nanotechnology has enhanced the time and CAR DNA delivery dependent efficacy of CAR therapy in all immune cells. Nanoparticles containing cationic polymers like polyethyleneimine (PEI), poly(L-lysine), and poly(2-dimethylamino) ethyl methacrylate effectively delivers DNA to the specific immune cells, thereby increasing the responsiveness towards the CAR therapy. In this review, we highlight promising avenues with potentials to improve clinical outcomes that have emerged from the convergence of nanotechnology and CAR based immunotherapy.

Triple-negative breast cancer (TNBC) remains lethal due to its aggressive molecular heterogeneity and drug resistance. We report a biomimetic nanoplatform (PLL/TNAAKT2@CM NPs) integrating biostable threose nucleic acid (TNA) with a donor-derived cell membranes (CMs) "cloak" for subtype-specific therapy. By complexing TNAAKT2 antisense oligonucleotides with poly-L-lysine (PLL) and coating them with TNBS-subtype membranes (MDA-MB-468 or MDA-MB-231), we achieve potent homotypic affinity. PLL/TNAAKT2@468CM NPs exhibited significantenhanced uptake in donor-matched basal-like 1 cells compared to heterotypic TNBC, non-TNBC and normal epithelial cells. Mechanistically, these nanoparticles internalize via a rapidmembrane-fusion, bypassing endosomal entrapment for direct cytosolic delivery. This facilitates robust silencing of the AKT2 oncogene, achieving a∼70% protein knockdown and outperforming conventional transfection reagents. In a drug-resistant MDA-MB-468 xenografts, systemic administration led to superior tumor accumulation, effective AKT2 knockdown, and significant tumor regression via the p21/Caspase-3 apoptotic axis, without systemic toxicity. This versatile "plug-and-play" strategy addresses tumor heterogeneity and endosomal sequestration, providing a transformative paradigm for targeted nucleic acid delivery in refractory cancers.

A biomimetic nanoplatform-reinforced hydrogel for multipronged STING suppression to remodel bone-immune homeostasis in diabetic periodontitis.

peri-Implant infections remain a major challenge to the long-term biointegration of dental implants, requiring coating strategies that simultaneously prevent bacterial infection and promote soft tissue integration. Here, we report a bifunctional polyelectrolyte multilayer Layer-by-Layer (LbL) coating combining poly(L-lysine) (PLL30), hyaluronic acid (HA), and fibronectin (Fn) rationally engineered through architectural control and translated from dip-coating to a clinically applicable spray-assisted deposition. Multilayers were fabricated by dip-coating, with Fn either intercalated throughout the film or confined to the outermost layers. Systematic optimization established that terminal confinement of Fn - Top-Layer Fn architecture (PLL30-HA)6 + (PLL30-Fn)6 - achieves complete inhibition of bacterial adhesion against Staphylococcus aureus and Aggregatibacter actinomycetemcomitans while maintaining cytocompatibility (78% human gingival fibroblast viability), whereas intercalating Fn throughout the film compromises cell compatibility, despite equivalent inhibition of bacterial adhesion. This architecture was successfully translated to a clinically scalable spray-assisted deposition using a dual-syringe spray device (coating time < 1 minute). Spray-coated titanium preserved bifunctionality achieving a significant reduction of S. aureus and a complete inhibition of A. actinomycetemcomitans, and 88% fibroblast viability after serum coating preconditioning. This work establishes a translational pathway of bifunctional coatings to clinical application, offering possibilities for both preventive and curative strategies against peri-implantitis and other implant-associated infections.

Deciphering Mn(II)/peroxymonosulfate system with nitrilotriacetic acid to degrade antibiotics: Roles of Mn species and interference of protein-like DOM.

Lung cancer has the highest global incidence and mortality, with nonsmall cell lung cancer (NSCLC) as the predominant subtype. Traditional therapies are limited by drug resistance, systemic toxicity, and poor precision. Active ingredients from Chinese herbs offer promising alternatives. This work identified kaempferol (KAE) from Tetrastigma hemsleyanum Diels et Gilg as an anti-NSCLC agent and developed a pH/photothermal dual-responsive nanocarrier (KMPB@PL-HA) for targeted therapy. The nanocarrier uses mesoporous Prussian blue (MPB) as the photothermal core, polylysine (PLL), and ultra-active hyaluronic acid (UL-HA) as the pH-responsive shell. In the tumor microenvironment (TME), UL-HA binds to CD44 receptors overexpressed on NSCLC cells and dissociates, while PLL enhances cellular uptake via electrostatic adsorption. KAE induces mitochondrial apoptosis via p-Akt inhibition, Bax/Bcl-2 regulation, and caspase cascade activation, and downregulates VEGF and modulates TME redox homeostasis for synergistic antitumor effects. This study provides a novel chemo-photothermal synergistic strategy for NSCLC.

ObjectiveLupus nephritis (LN) treatment faces the challenge of balancing effective immunosuppression with systemic safety. To address this, we aimed to develop a biomimetic nanoplatform capable of simultaneously targeting multiple pathogenic pathways in LN, thereby achieving potent immunomodulation without broad toxicity.MethodsA “smart immune decoy” (RAPA@MEX-PL) was engineered by encapsulating rapamycin (RAPA) in mesenchymal stromal cell-derived exosomes (MEX) and coating the surface with a cationic polylysine (PLL) corona. The platform was designed to concurrently: (1) the polylysine corona potently scavenges cell-free DNA (cfDNA) to quench TLR9-mediated inflammation, (2) the MEX core mediates the repolarization of macrophages from an M1 to an M2 phenotype, and (3) localized RAPA release provides durable mTOR inhibition, synergistically rebalancing autoimmune responses. Renal targeting, immunomodulatory activity, and systemic safety were evaluated in lupus-prone mouse models.ResultsIn lupus-prone mice, RAPA@MEX-PL demonstrated precise accumulation in renal tissue, leading to a significant reduction in auto-antibody levels and resolution of glomerular inflammation. The platform concurrently addressed three key pathogenic pathways—cfDNA scavenging, macrophage repolarization and mTOR inhibition—resulting in synergistic rebalancing of autoimmune responses. Notably, it circumvented the metabolic side effects typically associated with systemic RAPA administration.ConclusionsThe RAPA@MEX-PL nanoplatform represents a targeted and effective immunotherapeutic strategy for LN, capable of achieving sufficient immunosuppression without systemic toxicity. These findings emphasize its potential as a favorable candidate for the therapy for autoimmune diseases.

Linkage-chemistry-regulated activation of ferrocene-functionalized poly(l-lysine) nanoplatforms for synergistic chemotherapy and Chemodynamic therapy.

PAS domains mediate protein–protein interactionsthat enablefunctions such as sensing, signaling, dimerization, and localization.The photoactive yellow protein (PYP) from Halorhodospirahalophila is a model PAS-domain protein involved innegative phototaxis, yet its signaling partner remains unidentified.Here, we present a method to resolve protein orientations in PAS-domainsignaling by combining nano-FTIR and chiral vibrational sum-frequencygeneration (VSFG) spectroscopy with molecular dynamics simulationsand VSFG spectral calculations. As a demonstration, we used a chargedhomopolypeptide, poly-l-lysine (PLL), as a surrogate bindingsurface to probe PYP docking. We found that PYP adopts a preferredinterfacial orientation driven primarily by dipole–dipole interactions,despite its water-soluble, i.e., cytoplasmic nature. Remarkably, theinferred interaction surface and orientation closely match those observedin PYP homodimers and in a CNBh-PAS heterodimer. This methodologyenables in situ determination of protein orientational preferencesduring protein–protein interactions and may facilitate identificationof binding partners in PAS-domain signaling pathways.

A macroporous Poly(2-Hydroxyethyl methacrylate-glycidyl methacrylate) [Poly(HEMA-GMA)] cryogel functionalized with Poly(L-lysine) (PLL) and Cu(II) ions was developed for the efficient removal of the anionic dye Acid Blue 113 from water. The cryogel was synthesized via free-radical cryopolymerization of HEMA and GMA at − 20 °C, followed by covalent grafting of PLL through epoxy ring-opening reactions and subsequent coordination of Cu(II) ions with PLL amine groups. SEM analysis confirmed a highly interconnected macroporous structure, while BET analysis revealed specific surface areas ranging from 6.45 to 7.85 m2 g−1 and average pore diameters between 36 and 41 nm. Batch adsorption experiments demonstrated strong pH dependence, with maximum adsorption at pH 4.0. The Poly(HEMA-GMA)-PLL-Cu(II) cryogel exhibited a high adsorption capacity of 501.6 mg g−1 and reached equilibrium within 30 min, indicating rapid adsorption kinetics. Kinetic data were best described by the pseudo-second-order model, while equilibrium data fitted well to the Langmuir isotherm, suggesting monolayer adsorption on homogeneous active sites. Additionally, the Cu(II)-containing cryogel exhibited notable antibacterial activity against several Gram-positive and Gram-negative bacteria. These findings demonstrate that the developed cryogel combines high adsorption capacity, rapid kinetics, and antimicrobial functionality, making it a promising material for advanced wastewater treatment applications.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-026-47887-8.

Quantitative immunoassays of matrix Metalloproteinase-9 in tears using a contact Lens.

Resveratrol (RES) suffers from poor solubility and non-specific distribution, motivating the development of delivery systems with controllable stability and stimulus responsiveness. Here, we construct a hybrid nanocarrier composed of poly(N-isopropylacrylamide) and poly(L-lysine) that exhibits coupled temperature and pH responsiveness. Multiscale molecular simulations in explicit solvent, combined with quantum chemical optimization and free energy analysis, elucidate how external stimuli regulate carrier structure and RES release. At ambient conditions, RES is stably encapsulated within compact polymer clusters through cooperative noncovalent interactions. Elevated temperature induces hydrophobic collapse and structural reorganization, weakening polymer-drug interactions and enabling thermo-responsive release. Under acidic conditions, protonation of lysine segments triggers electrostatic repulsion and cluster dissociation, promoting drug desorption. These coordinated structural and energetic changes define a stimulus-driven "recognition-reconstruction-release" mechanism with tunable and predictable release behavior. Our findings provide molecular-level design principles for programmable nanocarriers targeting polyphenolic therapeutics.

Multilayer nanoarchitectonics of polypeptide capsules with size-selective permeability.

Immobilization of large biomacromolecules is often required for analytical quantification and physicochemical characterization. However, immobilization can alter the structure and size of the particles being studied. Here, two exosomes (derived from HEK-293 and MDA-MB-231 cells) and three viral particles (Suid herpesvirus 1 (SuHV), xenotropic murine leukemia virus (XmuLV), and porcine parvovirus (PPV)) were immobilized to different covalent chemistries to understand how surface chemistry influences particle deformation during immobilization. The surface chemistries explored were: (i) NHS (N-hydroxysulfosuccinimide) and EDC (1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide hydrochloride), and (ii) poly l-lysine (PLL) and glutaraldehyde (GA). Morphological changes in biomolecules following immobilization were quantified by measuring the height-to-diameter (H/D) ratios attained from atomic force microscopy (AFM) topographic images. These observations were further supported by complementary size and morphology analyses using dynamic light scattering (DLS) and liquid phase transmission electron microscopy (TEM). NHS/EDC chemistry consistently resulted in more significant particle flattening than PLL/GA, as evidenced by lower average H/D ratios across all biomacromolecules. Greater flattening effects were observed on the soft lipid envelope of exosomes as compared to viruses, due to differences in structural rigidity. Both immobilization chemistries resulted in a lower H/D ratio in tumor-derived MDA-MB-231 exosomes compared to nontumor-derived HEK-293 exosomes, likely due to the known softer mechanical properties of tumor-derived exosomes. Furthermore, immobilization of the enveloped viruses SuHV and XMuLV with NHS/EDC exhibited flattening effects and lower H/D ratios. Immobilization of nonenveloped PPV resulted in a low H/D ratio on NHS/EDC, which was likely due to particle aggregation rather than deformation. These findings provide valuable guidance for selecting appropriate surface chemistries for nanoscale biointerface studies and offer implications for surface-based diagnostics, high-throughput biosensing, and nanomaterial functionalization.

Poly(amidoamine) (PAMAM) and poly-L-lysine (PLL) dendrimers have emerged as highly versatile macromolecular platforms with significant potential in biomedical applications, owing to their well-defined architecture, tunable surface chemistry, and capacity for multivalent functionalization. Their ability to carry substantial molecular payloads and to be engineered for selective interactions with biological systems has positioned them as attractive candidates for targeted drug delivery, including the transport of boron-rich compounds. Recent advances in dendrimer chemistry have enabled the incorporation of boron clusters into PAMAM and PLL structures, creating hybrid systems designed to enhance cellular uptake, improve tumor selectivity, and increase boron accumulation within malignant tissues. Given the growing interest in boron neutron capture therapy (BNCT), the integration of boron clusters into dendrimer structures represents a particularly promising direction for enhancing boron delivery to tumors. This manuscript reviews current knowledge on PAMAM and PLL dendrimers and their boron-functionalized derivatives, summarizing findings from cell culture studies, in vivo models, and clinical or preclinical investigations. Particular attention is given to both the advantageous properties of these dendrimers-such as improved delivery efficiency and biocompatibility-and their potential undesirable biological effects. As such, PAMAM and PLL dendrimers represent an important and evolving class of carriers that may significantly advance the effectiveness of boron neutron capture therapy (BNCT) in cancer treatment.

Engineering cell adhesion: Poly-l-lysine-induced micro- and nanoscale surface modifications and their impact on cellular behavior and subcellular spectral signatures.

Phycotoxins are highly toxic compounds bioaccumulating in marine organisms, thus seriously affecting human health. Two electrochemical aptasensors for parallel detection of okadaic acid (OA) and saxitoxin (STX), exploiting a competitive strategy, are then proposed in this study. Screen-printed electrochemical cells were modified first by the electrodeposition of gold nanoparticles and then by the electropolymerization of poly(aniline-co-anthranilic acid) copolymer or poly(l-lysine) film. A conjugate between bovine serum albumin and each phycotoxin was immobilized covalently on the polymeric film and competed with the free phycotoxin in solution for the binding with a specific biotinylated aptamer. The competition was traced with an enzymatic conjugate between streptavidin and alkaline phosphatase: upon addition of 1-naphthyl phosphate, the enzymatic conversion of the substrate occurred. Differential pulse voltammetry (DPV) measurements were carried out to detect the enzymatic product 1-naphthol. A signal-off response was retrieved with detection limits of 66.4pg/mL for OA and 7.9pg/mL for STX, respectively. The aptasensors were also tested in the analysis of real mussel samples and their performance was compared with those of commercial enzyme-linked immunosorbent assays. The developed sensing strategy offers an efficient approach for monitoring OA and STX in seafood, thus representing a significant step towards ensuring consumer safety.

Microbial contamination in multidose ophthalmic drops primarily arises from bacteria surface adhesion and liquid backflow during use and storage. Traditional solutions relying on chemical preservatives or single-dose packaging face limitations concerning biocompatibility, environmental sustainability, and high cost. Therefore, the development of a bottle cap membrane that prevents backflow and bacterial contamination is crucial and highly meaningful. In this work, a series of cotton/polyurethane Janus composite membranes with unidirectional liquid transport, antibacterial, and bacteria-blocking functions were prepared by electrospinning and hot pressing technology. Remarkably, the structure of this composite membrane shows stable and excellent unidirectional liquid transport, with its one-way transport capacity (R) reaching grade 4 and its overall moisture management capacity (OMMC) reaching grade 5 (AATCC 195-2017). In addition, even after 50 times of washing, because polylysine (PL) is firmly fixed on cotton, the antibacterial rate of this composite membrane against S. aureus and E. coli still exceeds 99.9%. Moreover, depending on its micropore structure, its bacteria-blocking rate against S. aureus reached 99.4%, and its bacteria-blocking rate against E. coli also reached 76.9%. In addition to this, the composite membrane exhibits excellent biocompatibility, with a cell compatibility exceeding 75% and hemolysis below 5%. Collectively, this work provides a reliable solution to solve the problem of microbial pollution in the packaging of drug eye drops.

To evaluate the safety and efficacy of a newly developed catheter coated with antimicrobial poly-L-lysine (PLL) in reducing the risk of catheter-associated bacteriuria. A prospective, multicenter, randomized controlled noninferiority trial was conducted among patients who required indwelling catheterization between February 23, 2023, and January 30, 2024. The experimental group used antimicrobial PLL catheters, and the control group used noble metal alloys (NMA) coated catheters. The primary outcome was the incidence of catheter-associated bacteriuria. The secondary outcome was the total bacterial count per unit surface area of the catheter body in the urethra after catheterization. The safety evaluation included complications related to catheterization. The noninferiority threshold was set at 10%. Three hundred patients were enrolled, while the full analysis set (FAS) included 150 patients who received PLL catheters and 150 patients who received NMA catheters. There were 10 cases (6.9%) of bacteriuria in the experimental group and 15 cases (10.1%) in the control group. The difference in the incidence of bacteriuria between the experimental and control groups was - 3.1% (95% CI [- 7.2%, 6.6%], p = 0.3195). Four patients experienced symptoms compared to 6 in the control group during catheterization (p = 0.750). The proportion of patients experiencing abnormal urine white blood cells in the experimental group was lower (6.2% vs. 12.8%, p = 0.0194). The incidence of catheter-related adverse events was 3 cases (2.0%) in the experimental group and 6 cases (4.0%) in the control group (p = 0.5011). The short-term use of PLL catheters demonstrated noninferior efficacy in preventing bacteriuria compared with NMA catheters. The PLL catheters have good safety profile and low toxicity. Further trials involving more patients and long duration period are imperative to demonstrate the generalizability of the findings. This study was registered at https://www.chictr.org.cn/showproj.html?proj=188879 on February 3, 2023, and ID is ChiCTR2200059331.