ACS Applied Bio Materials最新文献

Apremilast (APST) is an effective medication for psoriasis, but its clinical application is limited by its exclusive availability as an oral tablet formulation and the associated systemic adverse effects. Hydrogel-based transdermal delivery offers a promising alternative for localized APST administration. To address this, Callicarpa nudiflora-derived extracellular vesicle-based hydrogel loaded with APST (APST-EV-Gel) was developed. APST was first loaded into Callicarpa nudiflora-derived extracellular vesicles (APST-EVs) with a drug loading of 17.14% ± 0.13% and an encapsulation efficiency of 41.49% ± 0.48%. The resulting APST-EVs were then embedded in a carbomer hydrogel to form APST-EV-Gel. Pharmacodynamic evaluation demonstrated that APST-EV-Gel significantly ameliorated skin lesions and reduced splenic inflammation in mice. The treatment also decreased infiltration of T-lymphocytes and neutrophils, downregulated the proliferation marker Ki67, and markedly lowered levels of the inflammatory cytokines TNF-α, IL-17, and IL-23. Furthermore, APST-EV-Gel promoted apoptosis in hyperproliferative keratinocytes, thereby contributing to disease alleviation. In conclusion, the combination of APST and EVs exerts superior therapeutic efficacy against psoriasis compared to monotherapy with either agent alone. APST-EV-Gel represents a promising topical therapeutic strategy for psoriasis.

Curcumin is a bioactive polyphenol exhibiting antibacterial and antiosteosarcoma properties; however, its clinical translation is constrained by poor aqueous solubility and low bioavailability. In this work, bioglass (BG) was incorporated into sol-gel-derived hydroxyapatite (HA) coatings on Ti6Al4V substrates to enable compositional control over curcumin release and biological response. HA coatings containing 1, 2.5, and 5 wt % BG were fabricated to investigate the influence of BG content on release behavior and multifunctional performance. Increasing BG content enhanced curcumin release by up to 1.4-fold at pH 5.0 and 1.6-fold at pH 7.4 relative to HA controls, consistent with increased coating degradation and microstructural changes associated with increasing BG content. The release profiles exhibited an initial burst followed by an asymptotic plateau, consistent with sustained release from the coating. BG-containing coatings also promoted osteoblast viability, increasing metabolic activity by up to 70% with BG alone and up to 86% in BG-containing curcumin-loaded coatings. In contrast, curcumin selectively reduced osteosarcoma cell viability by 67% after 11 days, accompanied by increased reactive oxygen species generation and mitochondrial dysfunction, suggesting oxidative stress-mediated cytotoxicity. Antibacterial testing demonstrated up to 78% reduction in Staphylococcus aureus viability after 72 h. These results demonstrate that compositional tuning of BG within HA coatings enables simultaneous control of drug release and selective biological responses, providing a multifunctional platform for orthopedic implants that supports osteoblast activity while mitigating infection and tumor recurrence risks.

Nanostructure-mediated targeted photothermal therapy (PTT) emerged as a minimally invasive frontier in precision oncology, offering the ability to ablate malignancies. The tailoring of the surface of nanostructures serves as the ultimate bridge between material design and targeted PTT. In this aspect, the surface of Ag2S nanoparticles (Ag2S NPs) was engineered with hydrophilic, organic architectures to achieve superior colloidal stability and selective cellular uptake, ultimately enabling light-triggered eradication of cancer cells. The successful formation of the monoclinic Ag2S phase was confirmed by XRD and TEM analyses, and its surface modification with cysteine was evident from FTIR and light scattering measurements. The developed water-dispersible and biocompatible cysteine-functionalized Ag2S NPs (Cy-Ag2S NPs) showed sufficient absorbance in near-infrared (NIR) region and also exhibited good photothermal heating efficacy under 808 nm laser light. In order to achieve site-selective targeting toward cancer cells, folic acid (FA) was introduced onto the surface of Cy-Ag2S NPs via EDC-NHS coupling. In vitro studies showed negligible cytotoxicity of FA-conjugated Cy-Ag2S NPs (FA@Cy-Ag2S NPs) under dark conditions, whereas pronounced cancer cell ablation was observed under NIR irradiation. Moreover, the FA@Cy-Ag2S NPs showed targeted behavior toward folate receptor (FR)-positive KB cells over FR-negative A549 cells through apoptotic induction, suggesting their potential application in targeted PTT.

In this study, a star-chained near-infrared responsive upconversion nanoparticle (UCNP)/Fe-TCPP nanocomposite (UFT) was fabricated via a two-step solvothermal method. Its phase, morphology, and structure were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and fourier transform infrared spectroscopy (FT-IR). Owing to electrostatic matching, UFT selectively targeted and killed Staphylococcus aureus. Under 980 nm irradiation at 1.0 W/cm2, 200 µg/mL UFT achieved a 98.46% bactericidal rate against 1 × 106 CFU/mL S. aureus within 18 min via a synergistic photodynamic/chemodynamic effect. In vivo wound healing experiments showed UFT promoted epidermal regeneration and accelerated wound repair. Radical trapping experiments coupled with electron spin resonance (ESR) spectroscopy identified superoxide anions (•O2-) and hydroxyl radicals (•OH) as the main reactive oxygen species involved in the process. These findings demonstrate that the as-prepared UFT nanocomposite exhibits both excellent near-infrared-responsive antibacterial performance and wound-healing efficacy, providing a promising experimental basis and theoretical foundation for the development of efficient photoresponsive antibacterial materials for the treatment of wounds infected with Gram-positive bacteria.

Implant manufacturing routes determine surface architecture and, consequently, modulate biointerface interactions that govern early biological responses. Although additive manufacturing has emerged as a promising alternative to conventional subtractive techniques, direct comparisons among commercially available systems remain limited. In this study, a commercially available additively manufactured dental implant was compared with four market-available conventionally machined systems to elucidate manufacturing route-dependent biointerface modulation. Physicochemical properties, surface topography, and electrochemical behavior were evaluated alongside biological responses. Protein adsorption profiles were characterized by liquid chromatography-tandem mass spectrometry (LC-MS/MS), while polymicrobial accumulation was quantified and profiled. Microbially induced surface degradation was assessed by titanium ion release. The additively manufactured implant and the market-leading conventional system exhibited higher surface roughness and distinctive topographical features, which were associated with reduced polymicrobial biofilm accumulation, lower titanium ion release following microbial challenge, and stable electrochemical behavior. Although conventionally machined implants exhibited broader proteomic profiles, functional enrichment analyses revealed overlapping biological categories among implant systems. Collectively, the findings demonstrate that the manufacturing route critically modulates implant biointerface characteristics, with additive manufacturing achieving performance comparable to established commercial systems.

Efficient drug delivery across both the tumor microenvironment and the blood-brain barrier (BBB) remains a major challenge in glioblastoma therapy, where dense cellular architecture and endothelial restriction severely limit treatment efficacy. Here, we report the rational design of a multifunctional nanoplatform, Dox[iRGD-GO@AgNP], integrating graphene oxide (GO), silver nanoparticles (AgNPs), and a cyclic iRGD tumor-penetrating peptide to enhance doxorubicin (Dox) transport, tumor penetration, and intracellular delivery. Comprehensive physicochemical characterization confirmed successful synthesis, surface functionalization, colloidal stability, and efficient drug loading. In two-dimensional C6 glioma cell monolayers, cyclic iRGD-functionalized nanohybrids demonstrated significantly enhanced intracellular Dox accumulation compared to free drug and nontargeted controls. These effects were further amplified in three-dimensional glioma spheroids, where Dox[iRGD-GO@AgNP] achieved deep tumor penetration (>80 µm) and more homogeneous intratumoral distribution. Enhanced delivery translated into superior therapeutic efficacy, as evidenced by reduced cell viability, increased membrane damage, upregulation of apoptosis-related markers (p53 and caspase-3 &9), and pronounced morphological disruption confirmed by fluorescence imaging and electron microscopy. To evaluate endothelial transport, a Transwell-based bEnd.3 BBB model was established and validated by transendothelial electrical resistance measurements and tight junction imaging. Cyclic iRGD-functionalized nanohybrids exhibited significantly enhanced transendothelial transport while preserving BBB integrity, indicating ligand-mediated transport rather than nonspecific barrier disruption. Importantly, improved BBB traversal resulted in increased drug accumulation in downstream glioma cells and spheroids. These composites showed anti-angiogenic properties in ovo CAM model. Overall, this study integrates rational nanocomposite design with a hierarchical in vitro evaluation framework spanning material characterization, tumor-relevant 2D and 3D models, and BBB transport. The Dox[iRGD-GO@AgNP] platform addresses key delivery and efficacy barriers in glioblastoma and provides a translationally relevant strategy for the development of BBB-penetrating nanotherapeutics.

Magnetic fluid hyperthermia (MFH) is an emerging localized cancer therapy that uses magnetic nanoparticles to selectively induce 42 to 45 °C mild hyperthermia within tumor tissues under alternating magnetic field to kill cancer cells. Despite encouraging clinical outcomes in glioblastoma and prostate cancer, the broader clinical translation of MFH across various tumor types remains limited by heterogeneous nanoparticle distribution, inconsistent tumor heating, and the frequent use of poorly predictive preclinical two-dimensional (2D) cultures. These conventional cultures fail to recapitulate the structural and stromal complexity of solid tumors and often overestimate therapeutic efficacy. In an attempt to recreate the cellular heterogeneity of clinical breast tumors to some extent, we developed a hetero-multicellular spheroid of breast cancer by co-culturing breast adenocarcinoma cells MCF-7, with non-cancerous murine fibroblasts McCoy. This approach generated heterospheroids that mimic certain key features of the breast tumor microenvironment, including heterogeneous cell population, fibroblast activation, collagen-rich extracellular matrix deposition, and the spatial arrangement of proliferative, quiescent, and necrotic cells. Following histologic validation, the hyperthermic potential of poly(acrylic acid)-coated Mn0.9Zn0.1Fe2O4 nanoparticle-based magnetic fluid on the heterospheroids was assessed under a 10 kA/m magnetic field strength and 332 kHz frequency. A single-session MFH inhibited heterospheroid growth and induced apoptosis; however, it did not significantly ablate the spheroids. Subsequently, two MFH sessions led to the complete elimination of the spheroids, accompanied by pronounced apoptotic activity. These findings suggest that repeated MFH can overcome thermotolerance, thereby augmenting therapeutic potential against stromal-rich breast tumors.

Despite bergenin (BER) having significant therapeutic benefits, its medicinal potential is hindered by its low natural abundance and poor aqueous solubility. Through host-guest complexation with cyclodextrins (CDs), this work offers an economical molecular approach to increase the bioavailability of BER. For the three native CDs (α-, β-, and γ-CD), γ-CD showed superior encapsulation properties. Octakis(6-O-sulfo)-γ-CD and Octakis(2,3,6-tri-O-methyl)-γ-CD were found to be the most suitable hosts for BER after additional screening of γ-CD derivatives. Strong non-bonded interactions and improved conformational stability were found for both complexes in microsecond-scale (2 μs) molecular dynamics (MD) simulations. Counterpoise-corrected DFT calculations at the B3LYP/6-31+G level showed more favorable complexation energy for the Octakis-methyl-γ-CD/BER complex (-52.34 kJ/mol) than for the Octakis-sulfo-γ-CD/BER complex (-33.81 kJ/mol), a trend that was consistently reproduced using the ωB97X-D/6-31G level of theory. Steered MD simulations demonstrated the unbinding mechanism of BER from CD. Higher electronic stability for the methylated complex (8.42 eV gap) than the sulfonated complex (7.01 eV) was shown by HOMO-LUMO orbital energy analysis. This higher stability of Octakis(2,3,6-tri-O-methyl)-γ-CD/BER was supported by two hydrogen bonds and one carbon-hydrogen interaction, as determined by IGMH analysis. The IR and UV-vis spectra of BER were also calculated and systematically compared with the corresponding experimental spectra. These molecular insights demonstrate that Octakis(2,3,6-tri-O-methyl)-γ-CD serves as a superior encapsulation host for BER, enhancing its therapeutic applicability.

Intervertebral disc degeneration remains a leading cause of chronic low back pain, and current disc replacement designs often fail to reproduce the behavior of the native intervertebral disc. This study evaluated chiral auxetic disc replacements incorporating polymeric and nanocomposite cores and compared them with a native L4-L5 disc model and a representative commercial implant. The finite element model included cancellous vertebral cores with cortical shells and was subjected to 2.8 mm axial compression and 7.5 N·m pure moments in flexion, extension, and lateral bending. Interfacial pressure, tangential contact stress, and sliding distance were evaluated under compression using pointwise agreement mapping, while posterior anterior-posterior displacement and strain energy were evaluated across all loading modes. The ultra-high molecular-weight polyethylene (UHMWPE) auxetic design provided the strongest overall performance among the proposed designs, with 31.25% pressure agreement and 49.33% sliding-distance agreement with the native disc, compared with 1.01% and 11.47%, respectively, for the commercial design. Graphene-reinforced UHMWPE produced the highest tangential contact stress agreement (34.06%) but reduced pressure and sliding-distance agreement relative to UHMWPE. UHMWPE also provided the closest strain energy response among the auxetic designs and closely reproduced the native posterior displacement during flexion. However, its range of motion remained substantially lower than the native disc, revealing a tradeoff between favorable compressive behavior and rotational compliance. These findings identify the UHMWPE chiral architecture as the most promising design evaluated while demonstrating the need for further geometric optimization to reduce bending stiffness.

Liposomal carriers are widely used for anticancer drug delivery due to their biocompatible nature in the biological milieu. Liposome-based drugs often face premature leakage, uncontrolled release, and insufficient control over long-term drug availability. Here, we present poly(lactic-co-glycolic acid) (PLGA)-coated mesoporous silica nanocarriers (PLGA-mSiO2, polysilomes) as an efficient and stable alternative to PEGylated liposomes. Such hybrid transporters are capable of efficiently encapsulating both hydrophilic [doxorubicin (DOX)] and hydrophobic [tamoxifen (TAM)] drugs. Investigation on drug loading, release kinetics, cellular uptake, and therapeutic response confirms the superior drug encapsulation and delivery of polysilomes efficiently. In liposomes, TAM was localized within the lipid bilayer, whereas DOX was actively loaded into the aqueous core through a transmembrane pH gradient. While this architecture enabled coloading, liposomes showed rapid drug release and pronounced cytotoxicity. In contrast, the core-shell structure of PLGA-mSiO2 polysilome carriers retained hydrophilic DOX within the mesoporous silica core and hydrophobic TAM within the PLGA shell. This compartmentalization ensures higher encapsulation efficiencies of both DOX (77.3%) and TAM (60.5%), with loading capacities of 59.3 and 50.4%, respectively. The PLGA-silica interface is a degradable diffusion barrier, enabling pH-responsive sustained release under acidic conditions. Moreover, PLGA-mSiO2 showed enhanced cellular uptake in MDA-MB-231 breast cancer cells and prolonged (up to 144 h) suppression of cell viability. These results present PLGA-coated mesoporous silica nanocarriers as a promising alternative to liposomal delivery by converting rapid drug release into sustained therapeutic activity.