ACS Applied Bio Materials最新文献

Abdominal aortic aneurysm (AAA) is a cardiovascular disease with potentially fatal consequences, yet effective therapies to prevent its progression remain unavailable. Oxidative stress is associated with AAA development. Carbon dots have reactive oxygen species-scavenging activity, while green tea extract exhibits robust antioxidant properties. However, the potential of green tea derived carbon dots in mitigating AAA progression has not been fully elucidated. In this study, tea polyphenol carbon dots (TP-CDs) were synthesized via hydrothermal methods and characterized for their antioxidant properties. The antioxidant effects of TP-CDs were evaluated, and TP-CDs' impact on phenotypic transformation, oxidative stress, apoptosis and ferroptosis was investigated comprehensively in an Ang II-induced AAA model, employing techniques such as Western blotting, flow cytometry, and immunohistochemistry. The results revealed that TP-CDs effectively alleviated oxidative stress induced by Ang II stimulation, thereby inhibiting phenotypic transformation, apoptosis, and ferroptosis in vivo. Furthermore, treatment with TP-CDs significantly attenuated AAA progression in a mouse AAA model. Overall, these findings demonstrate that TP-CDs reduced reactive oxygen species levels in the microenvironment and alleviated the progression of AAA, offering a promising therapeutic strategy for this condition.

Triple-negative breast cancer (TNBC) is known for its aggressive nature, typically presenting as high-grade tumors that grow and spread quickly in all breast cancer types. Several studies have reported a strong correlation between cancer and microbial infections due to a compromised immune system. The most frequent infection associated with surface malignancies, including breast cancer, is Candidiasis, which is majorly caused by Candida albicans. This study reports the development and characterization of the drug Baicalein (B) and NIR dye IR780 (IR) coloaded liposomes (BIRLs) as a multifunctional nanoplatform for treating fungal infections and TNBC. BIRLs were prepared by using hydrogenated soybean phosphatidylcholine as the lipid matrix, enhancing both the drug and dye solubility and therapeutic efficacy. The synthesized BIRLs-mediated photothermal therapy (PTT) exhibited significant synergistic antifungal efficacy when tested against C. albicans. The biocompatibility of BIRLs was studied in fibroblast cell lines and zebrafish embryos. BIRLs demonstrated promising photothermal and photodynamic effects, synergistically enhancing tumor ablation and reactive oxygen species (ROS) generation upon near-infrared (NIR) laser irradiation. In vitro studies revealed that BIRLs exhibit potent anticancer activity in two-dimensional (2D) cell cultures and three-dimensional (3D) tumor spheroids, significantly inhibiting cancer cell proliferation and migration. The dual therapeutic effect of BIRLs was additionally demonstrated by their ability to inhibit fungal growth, addressing common complications in cancer patients with compromised immune systems. Overall, the results highlighted the promising application of BIRLs as a versatile nanoplatform for synergistic cancer therapy and as an antifungal agent, with the potential to significantly improve outcomes for TNBC patients.

Threads coated with bioresponsive materials hold promise for innovative wearable diagnostics. However, most thread coatings reported so far cannot be easily customized for different analytes and frequently incorporate non-biodegradable components. Most optically active thread coatings rely on dyes, which often exhibit irreversible responses. In this work, we propose a biosensing coating for threads using curli fibers. Curli fibers are self-assembling fibers of the protein CsgA that can be genetically engineered to sense rapidly evolving diagnostic targets. We first established a simple electrostatic-mediated absorption protocol for coating anionic cotton threads with anionic curli fibers using an intervening cationic chitosan layer. We applied this protocol to two types of pH-sensing curli fibers, displaying either fluorescent pHuji or mCitrine proteins. This process ensures extensive curli coating over the entire thread surface using only water-based solvents. The resulting protein-coated threads are moderately hydrophobic, stretchable, and can monitor pH changes in real time through fluorescence. The coatings are also stable and functional on the surface for over 25 cycles of use, highlighting their potential for reusable practical applications. This straightforward and adaptable protocol can be extended to coat threads with diverse sensing and responsive capabilities for intelligent clothing.

Hemorrhage continues to pose a significant challenge in various medical contexts, underscoring the need for advanced hemostatic materials. Hemostatic hydrogels have gained recognition as innovative tools for addressing uncontrollable bleeding, attributed to their distinctive features including biological compatibility, tunable mechanical properties, and exceptional hemostatic performance. This review provides a comprehensive overview of hemostatic hydrogels that offer rapid and effective bleeding control. Particularly, this review focuses on hemostatic hydrogel design and associated hemostatic mechanisms. Additionally, recent advancements in the application of these materials are discussed in detail, especially in clinical trials. Finally, the challenges and potential advancements of hemostatic hydrogels are analyzed and assessed. This review seeks to emphasize the role of hydrogels in biomedical applications for hemorrhage control and provide perspectives on the innovation of clinically applicable hemostatic materials.

The development of stimuli-responsive drug delivery systems enables targeted delivery and environment-controlled drug release, thereby minimizing off-target effects and systemic toxicity. We prepared and studied tailor-made dual-responsive systems (thermo- and pH-) based on synthetic diblock copolymers consisting of a fully hydrophilic block of poly[N-(1,3-dihydroxypropyl)methacrylamide] (poly(DHPMA)) and a thermoresponsive block of poly[N-(2,2-dimethyl-1,3-dioxan-5-yl)methacrylamide] (poly(DHPMA-acetal)) as drug delivery and smart stimuli-responsive materials. The copolymers were designed for eventual medical application to be fully soluble in aqueous solutions at 25 °C. However, they form well-defined nanoparticles with hydrodynamic diameters of 50-800 nm when heated above the transition temperature of 27-31 °C. This temperature range is carefully tailored to align with the human body's physiological conditions. The formation of the nanoparticles and their subsequent decomposition was studied using dynamic light scattering (DLS), transmission electron microscopy (TEM), isothermal titration calorimetry (ITC), and nuclear magnetic resonance (NMR). ¹H NMR studies confirmed that after approximately 20 h of incubation at pH 5, which closely mimics tumor microenvironment, approximately 40% of the acetal groups were hydrolyzed, and the thermoresponsive behavior of the copolymers was lost. This smart polymer response led to disintegration of the supramolecular structures, possibly releasing the therapeutic cargo. By tuning the transition temperature to the values relevant for medical applications, we ensure precise and effective drug release. In addition, our systems did not exhibit any cytotoxicity against any of the three cell lines. Our findings underscore the immense potential of these nanoparticles as eventual advanced drug delivery systems, especially for cancer therapy.

Proteins are important biological macromolecules that perform a wide variety of functions in the cell and human body, and can serve as important biomarkers for early diagnosis and prognosis of human diseases as well as monitoring the effectiveness of disease treatment. Hence, sensitive and accurate detection of proteins in human biospecimens is imperative. However, at present, there is no ideal method available for the detection of proteins in clinical samples, many of which are present at ultralow (less than 1 pM) concentrations and in complicated matrices. Herein, we report an ultrasensitive and selective DNA-assisted CRISPR-Cas12a enhanced fluorescent assay (DACEA) for protein detection with detection limits reaching as low as attomolar concentrations. The high assay sensitivity was accomplished through the combined DNA barcode amplification (by using dual-functionalized AuNPs) and CRISPR analysis, while the high selectivity and high resistance to the matrix effects of our method were accomplished via the formation of protein-antibody sandwich structure and the specific recognition of Cas12a (under the guidance of crRNA) toward the designed target ssDNA. Given its ability to accurately and sensitively detect trace amounts of proteins in complicated matrices, the DACEA protein assay platform pioneered in this work has a potential application in routine protein biomarker testing.

Therapeutic angiogenesis has garnered significant attention as a potential treatment strategy for lower limb ischemic diseases. Although hepatocyte growth factor (HGF) has been identified as a key promoter of therapeutic angiogenesis, its clinical application is limited due to its short half-life. In this study, we successfully developed and characterized platelet membrane-coated HGF-poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). These nanoparticles demonstrated enhanced capabilities to promote endothelial cell (EC) proliferation, migration, and tube formation in vitro. Additionally, their efficacy in improving tissue perfusion and promoting angiogenesis was confirmed in a hindlimb ischemia rat model. Our findings suggest that platelet membrane-coated HGF-PLGA-NPs could serve as a promising therapeutic approach for enhancing angiogenesis and restoring tissue perfusion in ischemic conditions.

Synthetic ssDNA oligonucleotides hold great potential for various applications, including DNA aptamers, DNA digital data storage, DNA origami, and synthetic genomes. In these contexts, precise control over the synthesis of the ssDNA strands is essential for generating combinatorial sequences with user-defined parameters. Desired features for creating synthetic DNA oligonucleotides include easy manipulation of DNA strands, effective detection of unique DNA sequences, and a straightforward mechanism for strand elongation and termination. In this study, we present a split-and-pool method for generating synthetic DNA oligonucleotides on nanoparticles, enabling the creation of scalable combinatorial libraries. Our approach involves coupling DNA to nanoparticles, ligating double-digested fragments for orientation-specific synthesis, and attaching a final single-digested fragment to ensure strand termination. We assess the quality of our method by characterizing both the DNA and the nanoparticles used as solid supports, confirming that our method produces scalable, combinatorial nanoparticle-bound ssDNA libraries with controllable strand lengths.

Bacterial infections impede wound healing and pose significant challenges in clinical care. There is an immediate need for safe and targeted antivirulence agents to fight bacterial infections effectively. In this regard, bioderived nanovesicles have shown significant promise. This work demonstrated significant antibacterial properties of extracellular nanovesicles derived from plant (mint) leaf juice (MENV). A hydrogel (HG) was developed using oxidized alginate and chitosan and loaded with antibacterial MENVs (MENV-HG). This formulation was investigated for topical HG dressings to treat Gram-positive Micrococcus luteus and Gram-negative Escherichia coli-invasive wounds. The developed HG was injectable, biocompatible (>95% cell was viable), nonhemolytic (<5% hemolytic capacity), self-healing and exhibited strong physical and mechanical interactions with the bacteria cells (MENV-HG-treated bacteria were significantly more elastic compared to the control in both M. luteus (1.01 ± 0.3 MPa, p < 0.005 vs 5.03 ± 2.6) and E. coli (5.81 ± 2.1 MPa vs 10.81 ± 3.8, p < 0.005). MENV-HG was topically applied on wounds with a slow MENV release profile, ensuring effective healing. These in vivo results demonstrated decreased inflammation and expedited healing within 10 days of treatment (wound area closure was 99% with MENV-HG treatment and 87% for control). Taken together, MENV-HGs have the potential for a scalable and sustainable wound dressing strategy that works satisfactorily for bacteria-infected wound healing and to be validated in clinical trials.

Peptide building blocks have been recently proposed for the fabrication of supramolecular nanostructures able to encapsulate and in vivo deliver drugs of a different nature. The primary sequence design is essential for nanostructure property modulation, directing and affecting affinity for specific drugs. For instance, the presence of positively charged residues of lysine (K) or arginine (R) could allow improving electrostatic interactions and, in turn, the encapsulation of negatively charged active pharmaceutical ingredients, including nucleic acids. In this context, here, we describe the formulation and the multiscale structural characterization of hybrid cationic peptide containing hydrogels (HGs). In these matrices, the well-known low-molecular-weight hydrogelator, Fmoc-diphenylalanine (Fmoc-FF, Fmoc = fluorenyl methoxycarbonyl), was mixed with a library of cationic amphiphilic peptides (CAPs) differing for their alkyl chain (from C8 to C18) in a 1/1 mol/mol ratio. The structural characterization highlighted that in mixed HGs, the aggregation is guided by Fmoc-FF, whereas the cationic peptides are only partially immobilized into the hydrogelated matrix. Moreover, morphology, stiffness, topography, and toxicity are significantly affected by the length of the alkyl chain. The capability of the hydrogels to encapsulate negative drugs was evaluated using the 5-carboxyfluorescein (5-FAM) dye as a model.