Advanced Nanobiomed Research最新文献

Perfluorocarbons (PFCs) have been part of artificial oxygen carrier (AOC) research for decades. PFC-based AOCs stand out because of their characteristic physicochemical properties such as high gas solubility, low viscosity, high vapor pressure, and their chemical and biological inertness. For clinical use as red blood cell substitute for intravenous use or in machine perfusion of donor organs, PFCs require emulsification and stability in environments with high ionic strength, which is realized by the combination of albumin and lecithin as emulsifiers, resulting in ready-to-use lecithin-modified nanoscale oxygen carriers (LENOX). LENOX are the first PFC-based AOC, in which these two emulsifiers have been combined. The novel AOC LENOX result in improved physicochemical properties proven by higher zeta potential, smaller size, narrow particle size distribution, low molecular diffusion during storage as ready-to-use product, and high oxygen capacity. LENOX, in contrast to precursor formulations, are now compatible with a broad variety of clinically relevant solutions such as Steen Solution, Sterofundin ISO, or Custodiol, which allow the use of LENOX in numerous clinical scenarios such as blood replacement, transplantation, or preservation. LENOX show no cytotoxic effects in cell culture models and are therefore suitable for in vitro use.

In the quest to alleviate the severe side effects of chemotherapy, a promising approach is through prodrugs, an inactivate form of the drug that is administered systemically but activated locally. Bioorthogonal chemistry has the potential to generate high doses of drug at the tumor site with minimal off-target exposure. To harness the potential of bioorthogonal prodrugs, implantable heterogenous catalysts consisting of biocompatible polymers with immobilized metal nanoparticles are required. Polymers based on poly(2-hydroxyethyl methacrylate) with different levels of hydrophilicity are functionalized with either palladium nanocubes (≈10 nm) or palladium nanosheets (<200 nm). Using a palladium-sensitive fluorogenic model compound, propargylated resorufin, the nanosheets show higher catalytic activity than the nanocubes, as well as better metal retainment within the hydrogels. The more hydrophilic polymers show improved diffusion, conversion, and release and better recyclability. Converted product is sequestered by the polymer and released with delay, establishing a potential route to sustained release. These heterogenous catalysts can facilitate the clinical translation of bioorthogonal prodrugs.

Irisin, an exercise-induced myokine with anti-inflammatory and regenerative activity, is incorporated into dissolving poly(vinyl alcohol)/sucrose microneedle (MN) patches to enhance cutaneous wound repair. Recombinant irisin (0.5–1 μg mL⁻¹) is noncytotoxic to human fibroblasts and keratinocytes and significantly accelerates their migration in scratch and coculture assays. Dual-layer MNs exhibit sharp geometry and adequate fracture strength (0.08 N > 0.058 N insertion threshold) and release >90% of the loaded irisin within minutes. In a rat dorsal-wound model, both topical irisin and irisin-MN treatment hasten closure, but MN delivery produces deeper penetration and greater bioavailability, upregulating collagen III, SNAP25, and TGF-β1 while limiting excessive inflammation on H&E sections. Histology confirms thinner, better-organized granulation tissue and more complete reepithelialization in the irisin-MN group. These findings demonstrate that dissolving MNs provide a minimally invasive platform for localized irisin delivery, coupling the myokine's promigratory, angiogenic, and anti-inflammatory actions with efficient transdermal transport to achieve rapid, high-quality wound healing.

Nanoscale coordination polymers (NCPs) have emerged as a promising hybrid platform for drug delivery and cancer therapy. However, their potential in combination with radiotherapy (RT) remains largely unexplored. This study unveils a novel synergy between NCPs and RT, demonstrating a unique neutrophil-mediated tumor trafficking mechanism. Following X-ray irradiation, tumors recruit immune cells, particularly circulating neutrophils, which enhance NCP accumulation in the tumor by threefold. Notably, this effect is absent with other nanoparticles and operates independently of the enhanced permeability and retention effect. Immunostimulatory NCPs further leverage this mechanism to reshape the tumor microenvironment, promote immune cell infiltration, and enhance therapeutic efficacy. These findings underscore the potential of integrating NCP-based nanomedicines with RT to provide a targeted and effective cancer treatment strategy with strong translational promise.

Wearable wound health monitors can radically revolutionize the methods of contemporary wound care monitoring, thereby greatly reducing the burden on the healthcare system. By integrating sensors that can monitor parameters of the wound bed and interfacing them with wireless capabilities, continuous and remote monitoring can be achieved. The focus of this work is to demonstrate a system-on-chip, multiplexed wound healing monitor on a flexible wireless platform. A triangulated approach of measuring CRP, IL-6 proteins, pH, and temperature is used to wirelessly track changes in parameters that indicate the progress or lack thereof of wound healing. Further, to mimic functionality on skin conditions, the dependency of biomarkers and pH responses with temperature has been investigated. These systems can find imminent applications in clinical point-of-care diagnostics.

Pluripotent stem cells (PSCs), comprised of embryonic stem cells and induced PSCs, hold tremendous therapeutic potential. This has been driven by transformative advances in cell engineering and manufacturing, from fundamental research to clinical therapies. These innovations have come from a deeper understanding of developmental cell biology, the ability to recapitulate complex biochemical, mechanical, and topographical cues necessary for precise cell differentiation and functional maturation, and the deployment of advanced biotechnological approaches. For example, recent advances in micro- and nanotopographical engineering have introduced novel biomimetic approaches to enhance PSC adhesion, self-renewal, lineage specification, and spatial organization, while continued development of PSC manufacturing—including 3D bioreactor systems, microfluidic confinement devices, and scalable automation technologies—is driving a considerable shift beyond 2D culture and biochemical signaling methods. This mini-review examines the impact of recent developments in the application of micro- and nanotopographical cues in controlling core PSC fate and functions, including proliferation, adhesion, pluripotency, and differentiation. A gene expression profile can be altered by these topographical cues, and evaluate current strategies to integrate topographical control in PSC technology is highlighted.

Breast cancer remains among the most prevalent malignancies affecting women globally. Current treatment approaches, including mastectomy, chemotherapy, and radiotherapy, often fail to prevent cancer recurrence and can result in substantial tissue damage, esthetic concerns, and diminished quality of life. Three-dimensional (3D) bioprinting, stem cell-based technologies, and MXene nanomaterials show promise in tissue repair and cancer treatment. However, there is a lack of strategies that can offer multiple effects, preventing both breast tissue regeneration and tumor recurrence. In this study, we developed 3D hydrogel scaffolds incorporating stem cells and MXene quantum dots (MQDs) for in vivo application in a mouse model of breast cancer. We compared cellular, acellular, cellular MQD, and acellular MQD scaffolds transplanted into mouse after tumor resection and mastectomy. Notably, the acellular MQD group showed no tumor recurrence by day 14. It demonstrated superior tissue regeneration, confirmed by histological and immunostaining analyses. As a result, we offer a nanotechnological 3D scaffold based on hydrogel with dual functionality in preventing tumor recurrence and facilitating tissue regeneration. This innovative approach has the potential to revolutionize breast cancer treatment by reducing dependence on chemotherapy and radiotherapy. Thus, it offers a promising alternative for improving patient treatment outcomes.

Combined encapsulation systems offer promising solutions for delivering lipophilic compounds with stability and bioavailability limitations. This study develops a novel emulsion–core alginate-shell system for targeted delivery of lipophilic compounds to the proximal intestine. Using vitamin D₃ as a model drug, sunflower oil-based emulsion is encapsulated within core-shell beads. These beads are then compared to emulsion-filled gel beads, which are commonly studied for sustained gastrointestinal (GI) delivery. A 40% emulsion concentration is selected based on its 1-week stability in bottle tests. Core-shell beads maintained droplet size during encapsulation. Swelling and stability analyses under GI pH conditions show minimal impact on emulsion size and polydispersity. Core-shell beads exhibit higher swelling capacities of 8.232 g $��g^{�-�1�}�$ at pH 6.8 and 8.89 g $��g^{�-�1�}�$ at pH 7.4. Additionally, core-shell beads achieve 2.6% higher vitamin D₃ encapsulation efficiency. In simulated digestion, both bead types show low vitamin bioaccessibility in the stomach (<7%). In the intestinal phase, core-shell beads demonstrate superior performance, achieving 42.65% bioaccessibility within 30 min, compared to 41.65% for emulsion-filled gel beads after 2 h. These findings highlight the potential of core-shell beads combined with emulsion carriers for targeted delivery and controlled release of lipophilic compounds in the proximal intestine.

Tauopathies, a group of neurodegenerative disorders, are characterized by the abnormal aggregation of tau proteins into neurofibrillary tangles, driving synaptic dysfunction, neuronal loss, and disease progression through tau aggregate propagation. Graphene quantum dots (GQDs) functionalized with D-cysteine (D-GQDs) have shown promise in inhibiting tau aggregation and transmission via π–π stacking and electrostatic interactions with tau proteins. However, the nonspecific binding of GQDs to various proteins in the physiological environment, such as serum albumin, limits their clinical translation. In this study, the aim is to enhance the specificity of D-GQDs toward tau protein by incorporating a tau-targeting N-amino peptide, mxyl-NAP2. The mxyl-NAP2/D-GQD complex demonstrates improved selectivity for tau protein over serum albumin, effectively enhancing the inhibition of tau aggregation. To further minimize off-target effects and optimize therapeutic delivery, the mxyl-NAP2/D-GQD complex is loaded into small extracellular vesicles (sEVs), followed by functionalization of sEVs with neuron-targeting ligand, rabies viral glycoprotein peptides. This strategy not only reduces off-target effects, but also enhances uptake by neuron cells, which further improves inhibition of tau transmission between neurons. The results indicate that mxyl-NAP2/D-GQD-sEVs hold great promise for overcoming the off-target limitations of D-GQDs and advancing the development of precision therapeutics for neurodegenerative diseases.

Gold nanoclusters (AuNCs), known for their biocompatibility, intrinsic fluorescence, and magnetic properties represent an interesting nanomaterial for targeted drug delivery. Herein, a multifunctional platform is designed based on AuNCs modified with DNA strands for the loading and triggered release of doxorubicin (Dox), a chemotherapeutic agent. The surface of these nanoclusters is initially modified with a DNA strand and subsequently hybridized with a complementary DNA strand functionalized with folic acid (FA). The modification with FA facilitates targeted drug delivery to MCF-7 cells. The DNA on the AuNCs surface allows for the capture of Dox via intercalation. Cellular uptake and cytotoxicity are assessed in 2D cell culture and spheroid models. The results demonstrate a significantly higher uptake of the targeted AuNCs into MCF-7 cells compared to nontargeted counterparts. Moreover, under radiofrequency (RF) irradiation, the targeted AuNCs exhibit increased cytotoxicity. This cytotoxicity can be attributed to multiple factors, including hyperthermia induced by RF irradiation, heat-triggered release of the loaded drug, and the generation of reactive oxygen species (ROS). This research sheds light on the promising applications of AuNCs in cancer therapy, leveraging their unique properties for precise and effective treatment strategies.