ACS Applied Bio Materials最新文献

Intra-articular dexamethasone injection is an effective treatment for osteoarthritis. However, the drug has a short residence time in the joint cavity, necessitating frequent administration, which results in poor patient compliance and limits its clinical use. To address these problems, dexamethasone sustained-release microspheres (Dex-MS-2) with single-phase zero-order release behavior were prepared using polymer blending combined with a release promoter. Their characteristics, in vitro release, and in vivo pharmacodynamics were evaluated. Dex-MS-2 had a slightly larger mean particle size than Dex-MS-1, but exhibited a narrower particle size distribution and good encapsulation efficiency. Compared with microspheres prepared by polymer blending alone (Dex-MS-1), the microspheres containing the release promoter exhibited no release lag and achieved zero-order release for 28 days. Following intra-articular injection in rats, Dex-MS-2 exhibited favorable anti-inflammatory activity and effectively inhibited joint swelling, with superior therapeutic efficacy to Dex-MS-1 and comparable efficacy to the marketed injection. The Dex-MS-2 developed in this study reduced the frequency of administration, improved patient compliance, and achieved sustained drug release. This formulation may effectively overcome the limitations associated with the marketed formulation.

The fabrication of stable and highly performing enzyme-based electrodes is key for the effective generation of biodevices and bioelectronics, such as electrochemical biosensors. In this context, redox-active lyotropic liquid crystals based on 3D nanomaterials, known as lipid cubic phases (LCP), hold great potential due to the large specific surface area and the possibility of being functionalized. In this study, we functionalized a monoolein (MO) LCP matrix by incorporating an amphiphilic redox shuttle within its matrix with the aim of enhancing the electrochemical performance of a glucose oxidase (GOx) based electrode, and we investigated the stability of the overall system. The use of dodecyl(ferrocenylmethyl)dimethylammonium bromide (Fc12-Br) resulted in a progressive attenuation of its redox response during repeated potential cycling, consistent with cycling-induced blocking potentially involving Br^– electrosorption. To address this instability, counterion exchange from Br^– to hexafluorophosphate (PF₆^–) yielded Fc12-PF₆/MO. Both formulations were subsequently used to entrap GOx, and the resulting bioelectrodes were evaluated for their electrochemical responses to glucose. Although the initial glucose sensitivities of the Fc12-Br/MO/GOx and Fc12-PF₆/MO/GOx systems were comparable, the latter showed improved retention of its amperometric response during storage, retaining 80% ± 5% of its initial response to 6 mM glucose at day 20 under the tested conditions. Together with the improved electrochemical reversibility of the Fc12-PF₆/MO system under repeated redox cycling, these observations support counterion engineering as a promising strategy for improving the durability of redox-active lipid cubic phase bioelectrodes.

Oral delivery of water-repelling drugs for acute liver failure (ALF) often runs into problems like poor solubility, instability, and low absorption. In this work, we found that extracellular vesicles derived from honey (HEVs) can serve as a natural nanocarrier that works orally and targets the liver on its own. After isolating and characterizing these vesicles, we saw they are membrane-bound nanoparticles roughly 160 nm in size with a surface charge around –32 mV, and they contain proteins and RNAs. Oral HEVs mainly ended up in the liver and showed some anti-inflammatory activity without any drug loaded. To get better therapeutic effects, we loaded curcumin (Cur), a hydrophobic anti-inflammatory compound, into HEVs to make Cur@HEVs. These loaded vesicles greatly improved how well curcumin is absorbed and released in a sustained manner. In acetaminophen (APAP) caused ALF mice, oral Cur@HEVs improved liver function and survival much more than plain curcumin or empty HEVs did. Specifically, Cur@HEVs simultaneously put the brakes on pyroptosis (via the NLRP3/GSDMD/caspase-1 route) and necroptosis (through the RIPK1/RIPK3/MLKL pathway), which in turn cut down the release of inflammatory cytokines and kept liver cells from dying. Overall, HEVs come across as a safe, food-based nanocarrier that can be taken orally, and Cur@HEVs offer a bioactive platform for dually targeting inflammatory cell death in ALF. Our findings suggest that dietary extracellular vesicles warrant further investigation as potential therapeutic biomaterials, though additional translational studies are needed.

Biofilm accumulation on polymeric surfaces remains a persistent challenge in biomedical, industrial, and environmental systems. Here, we report an enzyme-responsive antifouling surface that integrates particle-generated topography with biologically activated surface renewal. Microparticles of poly(ethylene terephthalate) (PET) and the chitinase-responsive polymer PHEVD were generated by mechanical abrasion and embedded into poly(dimethylsiloxane) (PDMS) to create polymer-composite surfaces with three-dimensionally distributed microparticles. PET served as a nonenzyme-responsive control while PHEVD provided an enzyme-degradable phase designed to respond to bacterial activity. Particle-containing PDMS surfaces significantly reduced 24 h Escherichia coli RP437/pRSH109 biofilm biomass, with 2000-grit PHEVD surfaces producing the strongest inhibition and reducing biomass by 86 ± 3% relative to flat PDMS. In contrast, Pseudomonas aeruginosa PAO1 biofilm biomass after 24 h was not significantly reduced by either PET- or PHEVD-containing surfaces, indicating species-dependent early-stage antibiofilm behavior. However, after 7 days, PHEVD-containing surfaces significantly reduced mature PAO1 biofilm biomass. Under static culture, 600- and 2000-grit PHEVD surfaces reduced PAO1 biomass by 60.0 ± 5.5% and 71.0 ± 13.4%, respectively. Under shaking culture at 200 rpm, 600-grit PHEVD reduced retained PAO1 biomass by 93.6 ± 0.03% compared with flat PDMS and by 93.1 ± 0.03% compared with 600-grit PET. These results suggest that PHEVD-containing surfaces do not primarily prevent early PAO1 attachment but instead promote mature biofilm destabilization and removal. The observed 7-day PAO1 reduction is consistent with a coupled mechanism in which mechanical disturbance exposes PHEVD-rich domains, enabling PAO1-associated enzymatic activity to degrade the exposed PHEVD phase and weaken the biofilm-surface interface. This work establishes a facile strategy for designing biologically activated antifouling surfaces that convert microbial enzymatic activity into a trigger for prolonged biofilm control.

Due to their unique shape and tendency to undergo surface modification, anisotropic particles are emerging as next-generation particle-based systems for drug delivery applications, unlike conventional spherical particles. Nonetheless, in addition to geometric factors, the inherent characteristics of the polymer matrix significantly influence the development, dimensional stability, and functional behavior of these anisotropic systems. This review paper critically analyzes the impact of matrix materials, ranging from entirely polymeric systems to polymer–inorganic hybrids, on the structural evolution, compartmentalization, and physicochemical properties of anisotropic particles as a drug delivery system. Significant attention is directed to the influence of polymer characteristics, including molecular weight, glass transition temperature, hydrophobicity, and phase compatibility, on anisotropic morphology, multi-compartment formation, and drug encapsulation effectiveness. The interaction between the matrix composition and biological performance, encompassing cellular absorption, biological distribution, vascular margination, and stimuli-responsive medication release, is thoroughly examined. The significance of matrix-driven design in facilitating multi-drug distribution, regulating release kinetics, and achieving tailored therapeutic effects is emphasized. Notwithstanding considerable advancements, issues concerning scalable production, repeatability, and the uniformity of matrix-dependent parameters persist as substantial obstacles to clinical translation. This research establishes a structure–function–performance relationship for matrix materials, providing a solid foundation for the development of a future-oriented anisotropic polymeric drug delivery system.

Sonodynamic therapy (SDT) is an emerging strategy that uses ultrasound-mediated activation of a sonosensitizer to kill tumor cells via reactive oxygen species generation. While SDT has shown promise across multiple cancer types, its use in ovarian cancer remains largely unexplored. Chlorin e6 (Ce6) is an FDA-approved small molecule and well-established sonosensitizer. As the hydrophobicity of Ce6 limits its bioavailability, nanoparticle (NP)-based delivery is often required for sufficient bioaccumulation at target sites. While various nanocarriers have been explored for Ce6 delivery in ovarian cancer, such as graphene nanoribbons and inorganic metal oxides, these platforms face significant challenges for clinical translation. In this study, we evaluated two clinically relevant NP platforms, liposomes and poly(lactic-co-glycolic acid) (PLGA) NPs, in ovarian cancer spheroids and noncancerous human LP-9 mesothelial cells to compare Ce6 uptake, tumor specificity, and SDT efficacy. Liposome-Ce6 showed substantially higher uptake in OVCAR8 ovarian cancer spheroids relative to PLGA-Ce6 and free Ce6 at a Ce6 concentration of 0.3 µg/mL, with similar results observed in OVCAR3 and ID8 cancer models. Notably, liposome-Ce6 accumulated 76-fold higher in OVCAR8 spheroids than in LP-9 cells. This selective accumulation drove effective SDT-mediated tumor cell killing, with liposome-Ce6 eliminating 95 ± 4% of cancer cells following ultrasound irradiation while exhibiting significantly lower toxicity toward LP-9 cells. PLGA-Ce6 also enabled SDT-mediated tumor cell killing, though it required a 10-fold higher Ce6 dose than liposomes to achieve similar efficacy, increasing off-target toxicity toward LP-9 cells. Upon surface modification with poly-L-aspartic acid or hyaluronic acid, which are of interest for in vivo ovarian cancer targeting via layer-by-layer assembly, liposome-Ce6 maintained 8–11-fold higher tumor accumulation in OVCAR8 versus LP-9 cells and strong SDT efficacy. Overall, this study demonstrates that liposomes are a promising nanocarrier platform for further development of SDT approaches for treatment of ovarian cancer.

Organic supramolecular gels formed through the self-assembly of π-conjugated molecules such as azobenzenes, coumarins, perylenes, and pyrenes have emerged as versatile materials with diverse functional applications. These gels rely on noncovalent interactions, including hydrogen bonding and π–π stacking, enabling tunable mechanical, optical, and rheological properties. This review explores the self-assembly mechanisms of organic supramolecular gels and their applications in drug delivery, tissue engineering, environmental remediation, and sensing technologies. The relationship between molecular structure and gel performance is critically examined along with recent advancements in enhancing stability and responsiveness. While these materials offer exciting potential, challenges such as mechanical fragility, limited long-term stability, and scalability require further research. Future efforts should focus on designing supramolecular gels with enhanced robustness, biocompatibility, and adaptability to external stimuli. Addressing these limitations will pave the way for next-generation smart materials in biomedical, environmental, and industrial applications.

Root canal treatment (RCT) is the standard endodontic procedure for eliminating infection and preserving natural teeth. However, treatment failure can occur when residual bacteria persist within complex root canal anatomies, as current irrigation protocols do not provide direct confirmation of bacterial presence prior to obturation. Herein, we present SteriGP, an engineered Gutta-Percha (GP)-based proof-of-concept theranostic platform that integrates bacterial detection with localized photothermal disinfection during root canal treatment. SteriGP employs a ferricyanide-mediated bioreaction in which respiration-driven electron transfer from metabolically active bacteria promotes the in situ formation of Prussian blue (PB), providing a visible indicator of bacterial activity. The generated PB exhibits strong near-infrared (NIR) absorption and, upon 808 nm laser irradiation, produces localized hyperthermia for targeted photothermal inactivation of residual bacteria. SteriGP demonstrated concentration-dependent PB formation, photothermal heating, and antibacterial activity against both planktonic and biofilm models of representative Gram-negative (Escherichia coli) and Gram-positive (methicillin-resistant Staphylococcus aureus) bacteria. Furthermore, evaluation in an E. coli biofilm-based resin root canal model demonstrated visible bacterial detection within the canal and effective reduction of bacterial regrowth following NIR irradiation. Collectively, these findings establish the feasibility of integrating bacterial-responsive sensing and localized photothermal therapy into a Gutta-Percha platform for endodontic applications. While additional studies evaluating cytocompatibility, clinically relevant oral pathogens, natural tooth models, and in vivo performance are required, this work provides a foundation for the future development of theranostic biomaterials for precision-guided root canal treatment.

Extracellular vesicles (EVs) hold immense therapeutic potential, yet their clinical translation is hindered by nonspecific cellular uptake and the complexity and cost of surface engineering. Here, we present the EZON (Easy OligoNucleotide) EV modification platform, a cost-effective, post-isolation modification system that addresses both limitations simultaneously. The EZON platform employs unmodified DNA aptamers that bind directly to tetraspanin proteins on EV surfaces, eliminating the need for cholesterol conjugation, covalent chemistry, or genetic engineering of producer cells. EVs are thus easily and rapidly functionalized in a single incubation step at substantially reduced oligonucleotide cost. The EZON platform enables dual functionality: (1) the oligonucleotide anchor (ONA) sequence inhibits nonspecific cellular uptake, while (2) the display strand enables targeted delivery through ligand-mediated internalization. We demonstrate that our optimized ONA construct efficiently functionalizes EVs from multiple mammalian cell types. Cancer cells selectively internalized EZON-modified EVs functionalized with AS1411, an aptamer that targets nucleolin, whereas off-target internalization was suppressed. The platform's versatility extends to protein display via histidine-tag aptamers and therapeutic cargo delivery, as demonstrated by targeted doxorubicin delivery to head and neck squamous cell carcinoma cells. This rapid, modular approach transforms unmodified EVs into precision delivery vehicles within hours, offering a scalable solution for targeted therapeutics.

Magnetogenetics represents a new paradigm in biomedicine that employs magnetic nanoparticles (MNPs) as nanotransducers for remote, contactless control of cellular functions in vivo with high spatiotemporal resolution. This review systematically examines three fundamental physical principles underlying magnetogenetics: the magnetomechanical principle, which enables generation of piconewton-scale forces to activate mechanosensitive Piezo1/2 and TRPV4 channels; local “hot-spot” heating, which allows mild activation of thermosensitive TRPV1, TRPA1, and TRPM8 channels without macroscopic tissue temperature elevation; and the principle of magnetically triggered biochemical modulation, encompassing both the controlled release of signaling molecules and the generation of reactive oxygen species (ROS) for remote activation of intracellular cascades. The critical role of nanoparticle physicochemical design—including control over size, shape, doping, and surface functionalization—in achieving target specificity and efficacy is discussed. We review current advances in the application of these approaches to remotely actuated stimulation of cardiomyocytes, cell-specific modulation of neuronal circuits, metabolic regulation, and targeted anticancer therapy, including induction of ferroptosis and modulation of the tumor immune microenvironment. Particular emphasis is placed on key challenges for clinical translation, namely, ensuring specificity of MNP delivery, long-term biosafety of genetic constructs and nanoparticles, standardization of stimulation protocols, and addressing issues of magnetic field penetration depth and focusing precision. By integrating advances in nanotechnology, genetic engineering, and cell biology, magnetogenetics opens new avenues for personalized therapy of neurodegenerative, cardiovascular, and oncological diseases. However, the approach has been subject to significant physical and biological criticism, including fundamental questions regarding the thermodynamic feasibility of nanoscale heating and the mechanical sufficiency of single-particle forces—critiques that temporarily marginalized the field. This review critically examines these controversies and argues that while second-generation systems (e.g., high-moment synthetic nanoparticles and magnetoelectric nanodiscs) have partially alleviated these concerns, rigorous validation and reproducibility remain paramount. Nonetheless, magnetogenetics represents a promising remote alternative to existing methods of cellular modulation.