Advanced Nanobiomed Research最新文献

Extracellular vesicles (EVs) are gaining interest in regenerative medicine and biomaterials have been shown to extend EV bioavailability following delivery. Herein, the labeling of both hydrogels and EVs is reported to better understand hydrogel design for sustained EV release into tissues. Shear-thinning hydrogels are engineered using guest–host (i.e., adamantane–cyclodextrin) modifications to hyaluronic acid (GH), as well as GH hydrogels with the addition of gelatin crosslinked via transglutaminase (GH+Gel) to temporally control hydrogel properties. When labeled with a near-IR dye and injected into rat myocardial tissue, the GH+Gel hydrogel is retained (>14 days) longer than the GH hydrogel alone (≈7 days), likely due to the added gelatin network. To overcome challenges associated with common EV labeling methods, a highly versatile metabolic labeling methodology is utilized via the incorporation of N-azidoacetylmannosamine-tetraacylated during EV synthesis to introduce azide groups that can then be reacted with DBCO dyes. When injected in saline, EVs are cleared within 24 h in hearts; however, hydrogels enhance EV retention, with levels based on hydrogel degradation behavior, namely, >14 days for GH+Gel hydrogel and ≈7 days for GH hydrogel alone. These findings support the use of hydrogels in EV therapies.

Verteporfin (VP) has been used for photodynamic therapy (PDT) for over 20 years, and new applications have brought it back into the spotlight. VP is hydrophobic and requires lipid carriers for clinical delivery as Visudyne. A nanosuspension of VP, termed NanoVP, that requires no carriers is developed, permitting delivery of VP alone in an aqueous solution. NanoVP is produced by solvent–antisolvent precipitation, with dimethyl sulfoxide as the preferable solvent of several screened. The initial formulation has a hydrodynamic diameter of 104 ± 6.0 nm, concentration of 133 ± 10 μm, polydispersity index (Pdi) of 0.12 ± 0.01, and zeta potential of −22.0 ± 0.93 mV. Seeking a concentration >500 μm, a zeta potential <−10 mV, a diameter <64 nm, and a Pdi < 0.2, eight synthesis parameters are probed, identifying three that modified nanoparticle diameter and three that modified nanoparticle dispersity. The diameter is tuned fourfold from 49.0 ± 4.4 to 195 ± 7.1 nm, and the solution concentration is increased by 6.3-fold to 838 ± 45.0 μm. Finally, the bioavailability and anticancer capacity of NanoVP in glioblastoma are evaluated. In all, this provides a framework for the modification of amorphous nanoparticle properties and a new formulation for clinical use of VP.

Microscale carriers have emerged as promising materials for nurturing cell growth and as delivery vehicles for regenerative therapies. Carriers based on granular hydrogels have proved advantageous, where “microgels” can be formulated to have a broad range of properties to guide the behavior of adherent cells. Herein, the fabrication of osteogenic microgel matrices through the incorporation of laponite nanoclays is demonstrated. Forming a jammed suspension provides a scaffolding where cells can adhere to the surface of the microgels, with pathways for migration and proliferation fostered by the interstitial volume. By varying the content and type of laponite—RD and XLG—the degree of osteogenesis can be tuned in embedded populations of adipose-derived stem cells. The nano- and microstructured composite materials enhance osteogenesis at the transcript and protein level, leading to increased deposition of bone minerals and an increase in the compressive modulus of the assembled scaffold. Together, these microgel suspensions are promising materials for encouraging osteogenesis with scope for delivery via injection and stabilization to bone-mimetic mechanical properties after matrix deposition.

Engineering skeletal muscle tissue is crucial for the repair and replacement of damaged or dysfunctional muscle. Despite numerous studies emphasizing the significance of skeletal muscle engineering, challenges persist in effectively replacing or repairing large muscle sections in vivo. Bioreactors that facilitate the rapid expansion of muscle precursor cells present a promising solution for addressing extensive muscle loss. Specifically, bioreactors that mimic the native microenvironment of muscle tissue can induce biomimetic stimuli, selectively promoting the expansion of muscle precursors with optimal myo-regenerative potential. In this review, the advancements made in utilizing bioreactors to enhance the myo-regenerative phenotype of cells for skeletal muscle engineering are highlighted.

Electrophysiology Measurement

Human avatars like brain-on-a-chip and brain organoids use human-derived cells to replicate brain physiology. This review summarizes the latest methodologies for assessing the electrophysiology of various cell types within brain-on-a-chip and brain organoid models. More details can be found in article 2400052 by Jiyoung Song, Hoon Eui Jeong, Andrew Choi, and Hong Nam Kim.

Proton therapy is used to eradicate tumors in sensitive areas by targeted delivery of energy. Its effectiveness can be amplified using nanoparticles (NPs) as sensitizers, due to the production of reactive oxygen species at the NP's catalytically active surface, causing the cleavage of DNA. However, the impact of stabilizing macromolecular ligands capping the particles, needed for nanosensitizer dispersion in physiological fluids, is underexplored. Herein, ligand-free colloidal platinum NPs (PtNPs) fabricated by scalable laser synthesis in liquids are used, which allows studying particle and ligand effects separately. PtNPs are incubated with stabilizing concentrations of the clinically approved ligands albumin, Tween, and polyethylene glycol, and irradiated with proton beams at clinically relevant doses (2 and 5 Gy). At these doses, plasmid DNA cleavage larger than 55% of clustered DNA damage is achieved. Bovine serum albumin, Tween, and polyethylene glycol on the NP surface work as double-strand breaks (DSB) enhancers and synergetic effects occur even at low and clinically relevant particle concentrations and irradiation doses. Here, DSB enhancement by ligand-capped PtNP even exceeds the sum of the individual ligand and particle effects. The presented fundamental correlations provide selection rules for nanosensitizer design in proton therapy.

One-dimensional zinc oxide nanomaterials (1DZnO) have emerged as promising, cost-effective nanoplatforms with adjustable properties suitable for electrochemical and optical biosensing applications. In this work, modifications in the inherent photoluminescent response of 1DZnO are harnessed to develop a novel immunosensor tailored for detecting enteropathogenic Escherichia coli. This nanobiosensor demonstrates a modulation in photoluminescence signal, effectively responsive to analyte concentrations ranging from 1 × 10² to 1 × 10⁸ CFU mL⁻¹, with direct visualization of targeted bacterial cells over 1DZnO structures through scanning electron microscopy. The conceptualization of this nanobiosensor is focused on a real-time contact strategy that can significantly reduce processing and response times for pathogen detection, prospected for emergency scenarios. With this aim, the detection process unfolds in real time, with a mere 5–10 s interaction time, corroborated by the standard polymerase chain reaction approach. This synergistic validation underscores the reliability and precision of the developed biosensor. Notably, the utility of 1DZnO nanoplatforms extends beyond the realm of enteropathogenic E. coli, as the biosensing performance exhibited here holds promise for analogous applications involving other medically pertinent pathogens. This study paves the way for the broader implementation of 1DZnO-based biosensors in medical diagnostics, offering rapid, sensitive, and real-time detection capabilities.

Despite the recent wide investigation on active cancer drug delivery, there are still strong medical unmet needs for active tumor-environment responsive cancer drug delivery in terms of spatiotemporal control. Herein, a biohybrid system of pH-responsive peptide nanotubes (PNTs)-coated microalgae for active cancer drug delivery in response to the tumor-environment is developed. The amphiphilic PNTs are effectively used to encapsulate cancer drugs and coat the living microalgae of C. reinhardtii by electrostatic interactions. The drug-loaded PNTs-based biohybrid microalgae maintain agile movement with phototaxis behavior. After in vitro characterization and cytotoxicity assessment, it is shown that the biohybrid microalgae could be phototactically localized to the cancer cells and pH-responsively disassembled to release cancer drugs in a controlled manner. Finally, with the encapsulation of paclitaxel, the statistically significant suppression of tumor growth in xenograft tumor model animals is successfully demonstrated. Taken together, the feasibility of the multifunctional microrobotic platform for advanced cancer therapy is confirmed.

Since early developments in the field of mesoporous materials, mesoporous silica has attracted large interest in drug delivery, as they display an ordered array of pores with diameters ranging from 2 to 50 nm, which can be loaded with drugs. Mesoporous silica dissolves at physiological pH, triggering the release of loaded drugs. Several studies have focused on determining the key factors that determine the biodistribution, biocompatibility, and toxicity both in vitro or in vivo. However, in vivo studies focused on the degradation of mesoporous silica materials are very scarce, despite its relevance for drug release. In this perspective, recent works addressing mesoporous materials degradation in the context of drug delivery are discussed, first from a physicochemical point of view, and secondly in in vivo settings, in animal models that are the closest conditions to the encountered when the mesoporous materials are administered to humans. Finally, further discussion about the future directions in the design of mesoporous nanomaterials for therapy and for the study of their biological fate are presented.

The glioblastoma (GBM) tumor microenvironment is heterogeneous, complex, and being increasingly understood as a significant contributor to tumor progression. In brain tumors, the extracellular matrix contains a large concentration of hyaluronic acid (HA) that makes it important to study its role in cancer progression. In particular, abnormal accumulation of HA is observed in gliomas and is often associated with poor prognosis. In addition, HA is a polymer and its molecular weight (MW) distribution may influence tumor cell activity. Herein, the influence of the MW of HA on tumor cell metabolism is evaluated. A 2D cell culture approach is used to expose the U87-MG (medium glucose [MG]) cell line to different HA MWs (10, 60, and 500 kDa) and glucose concentrations (0, 5.5, and 25 mm). Notably, it is found that HA influences GBM amino acid metabolism via reduction in LAT1 transporter protein expression. Also an influence on mitochondrial respiration levels and a difference in the accumulation of some key products of cell metabolic activity (lactic acid, glutamic acid, and succinic acid) are reported. Overall, in these results, it is indicated that HA MW can influence GBM metabolic state, with implications for cell invasion and tumor progression.