ACS Applied Bio Materials最新文献

We report a high-performance ternary nanohybrid for surface-enhanced Raman scattering (SERS) biosensing that integrates sharp-tipped triangular silver nanoplates (TAgNPs) with two-dimensional (2D) exfoliated nano-mica platelets (NMPs) and carbon quantum dots (CQDs). TAgNPs were synthesized via a seed-mediated route and uniformly deposited onto the NMP surface, forming stable TAgNPs/NMPs nanohybrids that enabled a three-dimensional (3D) distribution of electromagnetic hot spots. CQDs were prepared hydrothermally using glucose and reduced glutathione as precursors and subsequently anchored onto the TAgNPs/NMPs surface. This interfacial modification improves energy-level alignment and promotes charge-transfer (CT) contributions, yielding TAgNPs/NMPs/CQDs nanohybrids. For adenine detection, the nanohybrids achieved a limit of detection (LoD) of 10^–9 M and an enhancement factor of 9.3 × 10⁸, with high signal uniformity (relative standard deviation, RSD = 7.4%). For Staphylococcus aureus sensing, the platform reached an LoD of 10 CFU mL^–1 and showed good reproducibility (RSD = 9.2%). Collectively, these results establish a scalable scaffold-stabilization and interface-functionalization co-design strategy for SERS substrates. Exfoliated NMPs act as a programmable 2D support that localizes and stabilizes near-field hot spots, enabling hierarchical 3D architectures. CQDs provide precise interfacial modulation and introduce CT-mediated pathways that enhance molecular capture and signal transduction. The resulting platform supports rapid pathogen screening and offers a generalizable materials blueprint for translational SERS biosensing.

We report the rational design and synthesis of nitrogen-doped sialic acid-derived carbon dots (SiaMPDA CDs) with excitation-independent green emission and high quantum yield and demonstrate their application as efficient Förster resonance energy transfer (FRET) donors for the selective detection of influenza A virus (IAV) subtypes. The surface functionalization of the CDs with sialic acid moieties enables specific molecular recognition of the viral hemagglutinin (HA) protein via multivalent hydrogen-bonding interactions. In combination with Rhodamine B (RhB) as an acceptor, the SiaMPDA–RhB pair exhibits efficient FRET under native conditions. Upon interaction with IAV (H3N2 and H1N1), the FRET system displays anomalous spectral behavior characterized by a simultaneous increase in both donor and acceptor emission intensities without any spectral shift. Mechanistic investigations suggest the formation of a ternary IAV–SiaMPDA–RhB complex, wherein long-range charge transfer coupled with FRET governs the observed fluorescence response. Control experiments with proteins, membrane vesicles, and liposomes confirm that the signal specificity arises from targeted interactions between the sialic acid functionalities of the CDs and the viral surface proteins. The sensing platform enables selective and sensitive detection of IAV subtypes in the picomolar range, comparable to existing carbon dot-based detection systems. These findings establish N-doped sialic acid carbon dots as promising nanoscale probes for virus detection and provide insights into charge-transfer-coupled FRET mechanisms in complex bionano interfaces.

Rheumatoid arthritis (RA) is a widespread joint disease that affects people across a wide range of ages. In RA, the viscoelastic properties of synovial fluid (SF) are significantly compromised, reducing its ability to protect cartilage surfaces during joint movements. Importantly, unlike osteoarthritis, hyaluronic acid (HA) viscosupplements are not effective for the treatment of RA, as they are prone to degradation in the lactic acid environment of RA-affected joints. Therefore, it is crucial to develop viscosupplements that can maintain viscoelastic properties in joints with elevated lactic acid levels. In the present study, we explore the microrheology of mucin-blended HA to maintain viscoelasticity in a simulated RA environment. The study reveals that the mucin-blended hyaluronic acid does not phase separate at higher lactic acid levels and is able to retain the required viscous and elastic behaviors as compared to a pure HA solution. Additionally, a morphological study using atomic force microscopy reveals that the addition of mucin to HA creates a fiber-bundle-like structure, which resists deformation under shear, in contrast to the fiber-like morphologies of pure HA that deform more readily. Furthermore, an interfacial microrheological study using a confocal laser scanning microscope reveals that mucin-blended HA exhibits reduced viscoelastic behavior at the collagen interface compared with pristine HA, suggesting potential boundary lubrication by reducing interactions between HA and the cartilage surface.

Plasmonic gold nanostars are promising photoactivatable platforms for cancer therapy, but their biological performance depends not only on light-to-heat conversion but also on how they interact with cellular interfaces before irradiation. Herein, we investigated silica-coated gold nanostars (AuNS@SiO₂) as NIR-responsive nanostructures in two colorectal cancer cell models, Caco-2 and HT-29, combining cellular assays with cell-derived Langmuir lipid models. AuNS@SiO₂ exhibited a plasmonic band centered at 810 nm, positive ζ-potential (+32.62 mV), and preserved photothermal activity, reaching 38.56 ± 1.79 °C under 810 nm irradiation, with a temperature increase of 14.71 ± 1.16 °C. In Caco-2 cells, AuNS@SiO₂ showed limited dark toxicity up to 160 μg mL^–1, with cell viability remaining above 94%, whereas NIR irradiation sharply reduced viability to 14.9 and 4.82% at 267 and 400 μg mL^–1, respectively. In contrast, HT-29 cells were more sensitive to AuNS@SiO₂ in the absence of irradiation, with viability decreasing to 38.0 and 28.1% at the same concentrations, indicating a stronger contact-associated response. Cell-derived Langmuir lipid models supported this interpretation: at 30 mN m^–1, AuNS@SiO₂ induced larger relative area expansions in HT-29 models, reaching 34.87 ± 1.04% at the 1:1 ratio, compared with 17.67 ± 1.16% for Caco-2. FTIR analysis showed that nanoparticle interaction mainly affected polar headgroup and interfacial regions, while the lipid acyl-chain region remained largely preserved. Together, these findings indicate that AuNS@SiO₂ elicit cell-line-dependent phototoxic profiles associated with membrane-related interactions, with Caco-2 displaying a predominantly light-amplified response and HT-29 showing a more contact-dominated response.

Cancer immunotherapy has attracted considerable attention since the early 2010s as an alternative to conventional cancer treatments such as surgery, chemotherapy, and radiotherapy. Among these approaches, cancer vaccines exert preventive and therapeutic effects by eliciting immune responses against tumor antigens. However, most cancer vaccines still rely on injection-based administration, which is associated with pain, the risk of secondary infection, and an increased burden on healthcare professionals. To address these limitations, we focused on noninvasive and convenient transdermal administration of cancer vaccines. Nevertheless, the transdermal delivery of hydrophilic cancer antigen peptides is considered challenging because the stratum corneum, the outermost layer of the skin, acts as a strong barrier against hydrophilic molecules and molecules with molecular weights greater than 500. To overcome this limitation, we developed a deep eutectic solvent (DES)-based formulation for transdermal cancer vaccination. In the present study, an amphiphilic DES composed of choline and oleic acid was prepared. Using this DES, a model cancer antigen peptide (SIINFEKL) was solubilized in an oil-based vehicle, yielding a transdermal formulation. Ex vivo studies demonstrated that the DES-based formulation exhibited greater skin permeation than a phosphate-buffered saline solution and a conventional ionic liquid-based formulation. Optimization with ethanol as a cosolvent yielded an advanced formulation that exhibited even higher skin permeation and showed significant tumor growth suppression in vivo. In addition, transepidermal water loss measurements after administration indicated that the advanced formulation caused little to no skin irritation. DES-based transdermal delivery systems may provide an effective strategy for overcoming the limitations of conventional injectable formulations. To our knowledge, this is the first report describing DES-based vaccine formulation with evaluation of its immunological efficacy.

The clinical effectiveness of doxorubicin (DOX) in hepatocellular carcinoma (HCC) remains constrained by poor tumor selectivity and the emergence of multidrug resistance. In this work, we examine how the electronic nature of the C-5 substituent on uracil-based nucleoside lipids shapes the physicochemical and biological behavior of DOX-loaded lipid nanoparticles (LNPs). Four ionizable lipids were designed, combining either thymidine (methyl, electron-donating) or 5-fluorouridine (FURD; fluorine, electron-withdrawing) head groups with α-tocopherol or cholesterol tails through a triazole linker, and synthesized via copper-catalyzed azide–alkyne cycloaddition, followed by formulation into DOX-LNPs. Notably, introducing the electron-withdrawing fluorine in FURD-based LNPs led to a clear improvement in DOX encapsulation efficiency (72–76% compared to 52–56%), enhanced pH-responsive drug release, and increased intracellular reactive oxygen species generation in HepG-2, Huh-7, and SK-Hep-1 cells. This redox perturbation triggers mitochondrial membrane depolarization, elevates Bax/Bcl-2 ratios, enhances cytochrome c release and caspase-3 cleavage, and induces pronounced S-phase arrest and apoptosis. Confocal microscopy further revealed markedly enhanced nuclear accumulation of DOX in the case of FURD-LNPs, while in vivo biodistribution studies showed clear preferential uptake in the liver. Density functional theory (DFT) calculations revealed distinct modulation of the frontier molecular orbital energy gap (E_HOMO–LUMO) between the substituents, providing a theoretical electronic rationale that strongly correlates with these empirical trends. Taken together, these findings suggest an important correlation between head-group inductive modulation and redox-driven anticancer activity, offering a promising molecular design strategy for nucleoside–lipid nanocarriers in HCC therapy.

The development of targeted and multifunctional anticancer nanoplatforms remains challenging due to limited selectivity, systemic toxicity, drug resistance, and off-target effects associated with conventional platinum-based chemotherapy. Zn(II) complexes have emerged as promising low-toxicity metal-based alternatives, exhibiting enhanced cytotoxicity toward cancer cells compared to healthy cells. In this study, a Schiff base ligand (K) was synthesized via condensation of 4-(1H-phenanthro[9,10-d]imidazol-2-yl)aniline and salicylaldehyde followed by complexation with Zn(II) to form a Zn(II) complex (S1). To enhance site-specific cellular uptake, Zn(II) complex S1 was encapsulated within folic acid-functionalized 10,12-pentacosadiynoic acid (FA-PCDA) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-based liposomes via molecular co-assembly, significantly improving stability and targeting capability. The resulting liposomal formulation of Zn(II) complex S1 (Lip-S1) exhibited characteristic fluorescence properties, enabling potential imaging applications. Lip-S1 selectively targeted folate receptor-expressing cervical cancer (HeLa) cells, demonstrating enhanced anticancer efficacy with a half maximal inhibitory concentration (IC₅₀) of 143.8 μg mL^–1 compared to free S1 and bare liposomes. Functional assays revealed that Lip-S1 inhibited cell proliferation, migration, and tumor spheroid growth while inducing apoptosis through mitochondrial membrane depolarization, elevated intracellular reactive oxygen species (ROS), caspase 3/7 activation, and modulation of apoptotic proteins (Bax upregulation, Bcl-2 downregulation). ROS scavenging studies confirmed that apoptosis is primarily mediated by oxidative stress linked to the PI3K/AKT (phosphatidylinositol 3 kinase/protein kinase B) signaling pathway. Enhanced cellular internalization of Lip-S1 relative to controls was also observed. These results highlight Lip-S1 as a targeted, fluorescence-trackable nanoplatform for ROS-mediated anticancer therapy.

Combined chemo–radionuclide therapy offers a promising strategy to improve cancer treatment by integrating various therapeutic mechanisms within a single drug delivery system (DDS). Metal–organic frameworks (MOFs), owing to their porous structure and tunable physicochemical properties, provide a unique platform for development of multifunctional DDSs. In this study, micro- and nanoscale UiO-66-NH₂ MOFs (mMOFs and nMOFs) were developed as ‘all-in-one’ DDSs for delivery of α-emitting radionuclide radium-223 (²²³Ra) and chemotherapeutic drug doxorubicin (DOX). The developed MOFs exhibited an octahedral morphology with sizes of ∼0.5 to 1 μm (DOX@mMOF) and ∼200 to 300 nm (DOX@nMOF). They demonstrated a high cellular uptake with no pronounced cytotoxicity (>90% at 4 mg/mL). In vivo biodistribution studies demonstrated high tumor retention of the developed DDSs. Importantly, combined ²²³Ra/DOX@mMOF and ²²³Ra/DOX@nMOF treatment resulted in significant tumor growth inhibition (61.2–72.1%). Histological and blood biochemical analyses revealed no detectable pathological changes. Overall, the developed UiO-66-NH₂-based DDSs displayed enhanced antitumor efficacy and demonstrated their potential for combined chemo–radionuclide therapy.

Additive manufacturing of engineered living materials (ELMs) enables the spatial patterning of living cells or organisms within three-dimensional (3D) polymer matrices. However, effective biocontainment, defined as the ability to retain cells within 3D-printed matrices during the application period, remains a key limitation for ELMs requiring physical confinement. While synthetic biology provides cell-specific biocontainment strategies, materials-based approaches can enable generic cell retention capabilities. Therefore, we applied a materials-based strategy that combines pre-printing formulation development and post-printing processing to increase the retention of yeast Saccharomyces cerevisiae in Pluronic F127-bisurethane methacrylate (F127-BUM) hydrogels. F127-BUM precursor solutions were formulated with the comonomers methacrylic acid (MAA) and/or 2-(dimethylamino)ethyl methacrylate (DMAEMA), extrusion-printed, UV-cross-linked, and immersed in 70 vol % ethanol for 60 or 300 s before cultivation. Comonomer addition preserved dimensional fidelity, thermoresponsiveness, and shear-thinning behavior for 3D printing. After immobilization and cross-linking, DMAEMA and higher concentrations of MAA considerably reduced yeast viability, whereas a 70-80% viability was observed for 0.03 and 0.06 mol L-1 MAA. With 0.06 mol L-1 MAA and 300 s ethanol immersion, the yeast retention time reached 98 ± 12 h, which was approximately 48% longer than that of the correspondingly treated F127-BUM-only control and represented about a 465% increase relative to the untreated F127-BUM-only control. After ethanol immersion, a peripheral growth-free zone developed around a metabolically active core, enhancing cell retention and contributing to delayed cell escape. The selected MAA-containing ELMs remained metabolically active and showed nearly 38% higher apparent glucose-to-ethanol conversion than treated F127-BUM-only controls. The suspension cultures fermented faster and achieved higher yield. Our method achieved enhanced biocontainment, with an operational window of about 4-5 days. In conclusion, we demonstrate that combining pre-printing and post-printing processes can enhance biocontainment for different ELM applications. We suggest the integration of this method with synthetic-biology strategies to further extend biocontainment duration for metabolically active living materials.

Single-walled carbon nanotubes (SWCNTs) are promising nanomaterials for cancer imaging and drug delivery owing to their near-infrared optical properties and tumor accumulation via the enhanced permeability and retention effect. Polyethylene glycol-modified phospholipids (PL-PEG) are widely used to disperse SWCNTs for in vivo applications; however, whether this formulation represents the optimal PEGylation strategy, particularly under repeated administration, remains unclear. Here, we perform a systematic head-to-head comparison between conventional 5 kDa PL-PEG/SWCNTs and SWCNTs encapsulated within a PEG-based cross-linked polymer network synthesized via CNT micelle polymerization. Quantitative biodistribution analysis using Raman spectroscopy demonstrates that cross-linked PEG/EAA/SWCNTs exhibit blood circulation profiles and tumor accumulation comparable to those of PL-PEG/SWCNTs following initial intravenous injection in mice. Striking differences emerge upon repeated dosing. PL-PEG/SWCNTs display reduced systemic exposure consistent with accelerated blood clearance (ABC)-like pharmacokinetics, accompanied by a trend of increased hepatic accumulation. In contrast, PEG/EAA/SWCNTs maintain largely preserved pharmacokinetic profiles (ABC index ≈ 0.8–0.9) and induce significantly lower anti-PEG IgM responses. These results suggest that the observed differences are attributable to differences in PEG molecular weight and/or PEG presentation architecture. By expanding the design space beyond the widely used PL-PEG standard, this study identifies PEG/EAA/SWCNTs as a promising alternative formulation for repeated-dose biomedical applications and highlights the importance of systematically evaluating PEG molecular weight and surface presentation in future studies.