Advanced Nanobiomed Research最新文献

Immune dysregulation is a pivotal factor in the onset and progression of various diseases. In cancer, the immune system's inability to discern and eliminate abnormal cells leads to uncontrolled tumor growth. When faced with resilient pathogens or harmful toxins, the immune system encounters challenges in clearance and neutralization. Achieving a delicate balance of pro-inflammatory and anti-inflammatory signals is essential in managing a range of disorders and diseases. Like in other biomedical research domains, nanotechnology has provided innovative approaches for rebalancing host immunity. Among the plethora of nanotechnology-based interventions, the concept of cell membrane-coated nanoparticles holds significant potential for immunomodulatory applications owing to their biomimetic properties that allow for precise interaction with the compromised immune system. This review thoroughly examines the potential of novel nanosystems for immune modulation. The exploration covers crucial elements, including the origins and characteristics of cell membranes, the methods employed for their procurement and coating, physicochemical/biological characterization techniques, and enhancement of their therapeutic efficacy via functionalization. Subsequently, case studies-based analysis of utilizing these bioinspired nanosystems in tackling different conditions caused by immune disturbance has been comprehensively discussed.

Skin pathological fibrosis conditions, such as hypertrophic scars (HS) and keloids, where the scar tissue is raised and extends beyond the original wound boundary, are aesthetically unappealing and sometimes painful or itchy, significantly impacting the life quality of patients. In this review, the advances of nanobiomaterials in treating skin pathological fibrosis are summarized and discussed. The focus is on the therapeutic approaches to cellular and molecular targets of HS, highlighting the potential of nanotechnology in scar management. The biofunctional nanomaterials can modulate inflammation, regulate angiogenesis, and promote fibroblast apoptosis. The nanotechnology-based drug delivery systems such as liposomes, ethosomes, and dendritic macromolecules can improve the solubility, stability, and efficacy of drugs, and enhance precise delivery, resulting in better outcomes in HS therapy. Integrating nanomaterials or nanostructures into hydrogels, nanofibers, and microneedles can enhance the biological functionality and maximize the therapeutic effect of nanoparticles (NPs) at the wound site. The important potential of nanotechnology-based scar treatment should be further explored to overcome the current challenges and promote its application in clinical practice.

Hydrogels have been extensively used for tissue engineering applications due to their versatility in structure and physical properties, which can mimic native tissues. Although significant progress has been made toward designing hydrogels for soft tissue repair, engineering hydrogels that resemble load-bearing tissues is still considered a great challenge due to their specific mechanophysical demands. Herein, microporous, tough, yet highly compressible poly(vinyl alcohol) (PVA)-based hydrogels are reported for potential applications in repairing or replacing different load-bearing tissues. The synergy of freeze-thawing and the Hofmeister effect, which controlled the spatial arrangement and aggregation of polymer chains, facilitated the formation of microstructured frameworks with tunable porosity. While the maximum mechanical strength, toughness, and stretchability of the engineered hydrogel were ≈390 kPa, ≈388 kJ m⁻³, and ≈170%, respectively, Young's modulus based on compression testing wasfound to be in the range of ≈0.02–0.30 MPa, highlighting the all-in-one mechanically enriched nature of the hydrogel. Furthermore, the minimal swelling and degradation rate of the engineered hydrogel met the specific requirements for load-bearing tissues. Finally, excellent antibacterial resistance as well as in vitro biocompatibility of the hydrogel demonstrates its potential for the replacement of load-bearing tissues.

Many types of cancer are currently treated using a combination of chemotherapeutics, but unfortunately, this strategy is considerably limited by severe side effects. The current development of nanocarriers enables the use of multiple drugs anchored on one unique platform thus enhancing the initiated therapeutic effect and minimizing the possibility of drug resistance. In this context, a graphene-oxide-based 2D nanoplatform is developed, which is functionalized using highly branched polyethylene-glycol and a multimodal set of two drugs with various mechanisms of action, namely Pt-based complex (a Pt(IV) prodrugs based on cisplatin) and doxorubicin (DOX). We performed in vitro 2D screening on two cancer cell lines, namely glioblastoma and osteosarcoma, that were selected as models of two aggressive tumors that remain a massive challenge in oncology. The therapeutic effect of the developed nano-platform is higher at lower concentrations (15 μm of Pt-drug, 0.6 μm DOX) compared to the impact of the free drugs. This indicates a possible positive effect of the accumulation and transport of the drugs using this nanoplatform. Results obtained on 3D cell models using MG63 osteosarcoma cells uncovered an understandable lowered diffusion profile of the developed nanoplatforms, compared to the application of free drugs.

New advancements in nanocarrier technologies are revolutionizing the delivery of drugs through the skin, allowing for precise treatment with better absorption, stability, and bioavailability. This review investigates lipid and inorganic nanocarriers like liposomes, ethosomes, and inorganic nanoparticles and assesses their potential for delivering drugs through the skin. It emphasizes the mechanisms that enable controlled release and deeper skin penetration, which are crucial for ensuring effectiveness in clinical applications. The review synthesizes existing research, acknowledging that only few nanocarriers are successfully deployed in clinical settings. By offering a comprehensive overview, it sheds light on the progress and future obstacles to using nanocarriers for drug delivery through the skin.

To date, animal models are still indispensable for studying biodistribution and elimination of nanomaterials. However, the use of mammals for in vivo experiments faces various challenges including increasing regulatory hurdles and costs. This study aims to validate larvae of the domestic silkworm Bombyx mori as an alternative invertebrate model for preliminary in vivo research. Organ distribution and elimination of gold nanoparticles (AuNPs) are compared with four different surface functionalities in silkworms after systemic administration: AuNPs coated with poly(ethylene glycol) (PEG), with polyglycidols (PGs) that are slightly hydrophobic (PG(alkyl)), positively charged (PG(+)), or negatively charged (PG(−)). Subsequent inductive coupled plasma mass spectrometry 6 or 24 h after AuNPs administration reveals the biodistribution in silkworm hemolymph, midgut, epidermis, and excrements. Even after 24 h incubation, hemolymph contains the highest AuNPs concentrations, independent of surface functionalization indicating a prolonged circulation time and slow distribution into different silkworm organs and tissues. Positively charged PG(+)AuNPs show three times higher concentrations in the midgut and are excreted at the fastest rate when compared to other AuNPs. In the findings, a surface-dependent biodistribution and elimination of AuNPs are indicated in silkworms, and the feasibility of using this inexpensive animal model for time- and cost-effective, preliminary in vivo studies of NPs is confirmed.

Ongoing obstacles in preclinical drug testing have raised significant concerns within the pharmaceutical industry. Recently, utilizing the potential of three-dimensional (3D) bioprinting offers a solution for creating tissue models for screening of the effectiveness and safety of new drugs. In this study, the anti-inflammatory potential of garlic extracts is assessed, specifically N-Benzyl-N-methyl-dodecan-1-amine (BMDA), using a 3D bioprinted artificial skin model. Comprehensive physicochemical characterization and immunocytochemical analysis demonstrate that the 3D bioprinted skin model exhibits structures and functions resembling human skin. BMDA treatment in a prepared skin model reveals its capacity to mitigate H₂O₂-induced oxidative stress and trigger anti-inflammatory responses. Notably, BMDA reduces the expression of pro-inflammatory cytokines and chemokines by downregulating NF-κB and mitogen-activated protein kinase inflammatory signaling pathways. In summary, our findings highlight the potential of an artificial skin model as a robust platform for the development of new drugs.

Electrocardiogram (ECG) monitoring has recently been an important indicator of cardiac health diagnosis. In the past, ECG could be measured under limited conditions in hospitals with 12-lead electrode systems. Recently, portable and wearable devices have offered continuous, real-time monitoring of ECG signals in real life. However, developing wearable ECG sensors that provide low-motion artifacts and high-quality signals during exercise conditions is still challenging. Herein, this review reports a systematic summary of the key characteristics, properties, and requirements of flexible wearable ECG devices for the early diagnosis of heart dysfunction in dynamic motions, including exercise. In addition, the recent progress in controlling sensor adhesion and novel materials for designing dry electrodes are discussed to improve ECG signal quality in exercise. Finally, various aspects of electrode developmental challenges and limitations are reviewed, and research directions for future studies are discussed.

Assessing B cell affinity to pathogen-specific antigens prior to or following exposure could facilitate the assessment of immune status. Current standard tools to assess antigen-specific B cell responses focus on equilibrium binding of the secreted antibody in serum. These methods are costly, time-consuming, and assess antibody affinity under zero force. Recent findings indicate that force may influence BCR-antigen binding interactions and thus immune status. Herein, a simple laminar flow microfluidic chamber in which the antigen (hemagglutinin of influenza A) is bound to the chamber surface to assess antigen-specific BCR binding affinity of five hemagglutinin-specific hybridomas from 65 to 650 pN force range is designed. The results demonstrate that both increasing shear force and bound lifetime can be used to enrich antigen-specific high-affinity B cells. The affinity of the membrane-bound BCR in the flow chamber correlates well with the affinity of the matched antibodies measured in solution. These findings demonstrate that a microfluidic strategy can rapidly assess BCR-antigen-binding properties and identify antigen-specific high-affinity B cells. This strategy has the potential to both assess functional immune status from peripheral B cells and be a cost-effective way of identifying individual B cells as antibody sources for a range of clinical applications.

Despite success in the treatment of some blood cancers and melanoma, positive response to immunotherapies remains disappointingly low in the treatment of solid tumors. The context of the molecular crosstalk within the tumor microenvironment can result in dysfunctional immune cell activation, leading to tumor tolerance and progression. Although modulating these protein–protein interactions (PPIs) is vital for appropriate immune cell activation and recognition, targeting nonenzymatic PPIs has proven to be fraught with challenges. To address this, a synthetic, multivalent molecular modality comprised of small interfering peptides precisely hybridized to a semirigid DNA scaffold is introduced. Herein, a prototype of this modality that targets the IL-33/ST2 signaling axis, which is associated with tumor tolerance and immunotherapy treatment failure is described. Using peptides that mimic the specific high-energy “hotspot” residues with which the IL-33/ST2 coreceptor, IL-1RAcP, interacts with the initial binary complex, this platform is shown to effectively bind IL-33/ST2 with a K_D of 110 nm. Additionally, this molecule effectively abrogates signal transduction in cell models at high nanomolar concentrations and is exquisitely selective for this complex over structurally similar PPIs within the same cytokine superfamily.