Search Results (381)

Fluorescent dyes, such as cyanine dyes, are widely used in fluorescence-imaging-guided tumor therapy due to their high absorbance and fluorescence quantum yield. However, challenges persist in optimizing the performance of fluorescent nanoparticles, particularly due to the aggregation-caused quenching (ACQ) effect of cyanine dyes. Here, a novel counterion construction strategy is introduced using cyanine dye as a model ACQ dye. Through dynamic-controlled flash nanoprecipitation, fluorescent nanoparticles (CyINPs) with tunable structures are developed, investigating the effects of various factors, including counterions, block copolymers, and dye concentrations, on CyINPs’ stability and fluorescence enhancement. The optimized CyINPs with good water solubility show a 21-fold increase in fluorescence intensity and a 3.5-fold increase in encapsulation efficiency compared to CyINPs prepared by a thermodynamic-driven method. Under the efforts of polymers and counterions, dyes are separated, which reduces the impact of the ACQ effect and results in stronger fluorescence intensity, providing insights into improving nanoparticle biocompatibility and energy utilization efficiency. Full article

This study focused on the poly(DL-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(DL-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer, which was recently reported as a novel material for polymeric nanoparticles to replace poly(DL-lactide-co-glycolide) (PLGA) as a drug carrier for prednisolone (PSL), and aimed to evaluate the efficacy of PSL-loaded PLGA-PEG-PLGA nanoparticles (NPs) against allergic contact dermatitis (ACD). PSL-loaded PLGA-PEG-PLGA NPs were prepared using the nanoprecipitation method, and their particle size distribution and mean particle size were measured using dynamic light scattering. 1-Fluoro-2,4-dinitrobenzene (DNFB) was used to create a mouse model of contact hypersensitivity (CHS). PSL-loaded PLGA-PEG-PLGA NPs were administered before sensitization with DNFB, and the therapeutic effect was evaluated by quantifying intracutaneous TNF-α and IL-4 levels suing ELISA. When PSL-loaded PLGA-PEG-PLGA NPs were administered before sensitization, TNF-α expression and IL-4 statements were significantly lower in the PSL-loaded PLGA-PEG-PLGA NP group than in the non-treated group. No significant difference was observed between the PSL-loaded PLGA-PEG-PLGA NP and PSL-loaded ointment groups, even though the steroid dose was 40 times lower than in the PSL-containing ointment. These results suggest that PSL-loaded PLGA-PEG-PLGA NPs may have a better effect in the treatment of ACD than PSL-loaded PLGA NPs. Full article

Lipid nanoparticle (LNP)-based delivery systems are promising tools for advancing RNA-based therapies. However, there are underlying challenges for the oral delivery of LNPs. In this study, we optimized an LNP formulation, which we encapsulated in a pH-sensitive Eudragit^® S 100 (Eu) coating. LNPs were prepared using the DLin-MC3-DMA ionizable lipid, cholesterol, DMG-PEG, and DSPC at a molar ratio of 50:38.5:10:1.5. LNPs were coated with 1% Eu solution via nanoprecipitation using 0.25% acetic acid to get Eu-coated LNPs (Eu-LNPs). Particle characteristics of LNPs were determined by using dynamic light scattering (DLS). Ribogreen and agarose gel retardation assays were used to evaluate nucleic acid entrapment and stability. LNPs and Eu-LNPs were ~120 nm and 4.5 μm in size, respectively. Eu-LNPs decrease to an average size of ~191 ± 22.9 nm at a pH of 8. Phosphate buffer (PB)-treated and untreated Eu-LNPs and uncoated LNPs were transfected in HEK-293 cells. PB-treated Eu-LNPs showed significant transfection capability compared to their non-PB-treated counterparts. Eu-LNPs protected their nucleic acid payloads in the presence of a simulated gastric fluid (SGF) with pepsin and maintained transfection capacity following SGF or simulated intestinal fluid. Hence, Eu coating is a potentially promising approach for the oral administration of LNPs. Full article

A Cu-11.85Al-3.2Mn-0.1Ti shape memory alloy (SMA) with excellent superelasticity and shape memory effect was successfully fabricated via selective laser melting (SLM). Increasing the energy density enhanced grain refinement, achieving a 90% refinement rate compared to cast alloy, with an average width of ~0.15 µm. Refined martensite lowered transformation temperatures and increased thermal hysteresis. Nanoscale Cu₂TiAl phases precipitated densely within the matrix, forming a dual strengthening network combining precipitation hardening and dislocation hardening. This mechanism yielded a room-temperature tensile strength of 829.07 MPa, with 6.38% fracture strain. At 200 °C, strength increased to 883.68 MPa, with 12.26% strain. The maximum tensile strength represents a nearly 30% improvement on existing laser-melted quaternary Cu-based SMAs. Full article

Background: Lipid nanoparticles (LNPs) represent one of the most effective non-viral vectors for nucleic acid delivery and have demonstrated clinical success in siRNA therapies and mRNA vaccines. While considerable research has focused on optimizing ionizable lipids and helper lipids, the impact of PEGylated lipid content on LNP-mediated mRNA delivery, especially in terms of in vitro transfection efficiency and in vivo performance, remains insufficiently understood. Methods: In this study, LNPs were formulated using a self-synthesized ionizable lipid and varying molar ratios of DMG-PEG2000. Nanoparticles were prepared via nanoprecipitation, and their physicochemical properties, mRNA encapsulation efficiency, cellular uptake, and transfection efficiency were evaluated in HeLa and DC2.4 cells. In vivo delivery efficiency and organ distribution were assessed in mice following intravenous administration. Results: The PEGylated lipid content exerted a significant influence on both the in vitro and in vivo performance of LNPs. A bell-shaped relationship between PEG content and transfection efficiency was observed: 1.5% DMG-PEG2000 yielded optimal mRNA transfection in vitro, while 5% DMG-PEG2000 resulted in the highest transgene expression in vivo. This discrepancy in optimal PEG content may be attributed to the trade-off between cellular uptake and systemic circulation: lower PEG levels enhance cellular internalization, whereas higher PEG levels improve stability and in vivo bioavailability at the expense of cellular entry. Furthermore, varying the PEG-lipid content enabled the partial modulation of organ distribution, offering a formulation-based strategy to influence biodistribution without altering the ionizable lipid structure. Conclusions: This study highlights the critical role of PEGylated lipid content in balancing nanoparticle stability, cellular uptake, and in vivo delivery performance. Our findings provide valuable mechanistic insights and suggest a straightforward formulation-based strategy to optimize LNP/mRNA systems for therapeutic applications. Full article

The effect of severe plastic deformation during milling and conventional and Spark Plasma Sintering (SPS) on the wt. % microstructural, structural, thermal, magnetic, and mechanical properties of the Al–16 wt. % Mn–7 wt. % Cu alloy was studied. A milling process for up to 24 h (A24) leads to microstructure refinement and the presence of Al, Mn, and Cu solid solutions. The energy dispersive spectroscopy (EDS) analysis reveals the existence of Cu–Al, Mn–Al, and Al–Mn enriched particles. The powders exhibit weak ferromagnetism and an exchange bias (EB) behaviour that decreases with increasing milling time. The Ms values fitted using the law of approach to saturation (LAS) are comparable to the experimental values. The exothermic and endothermic peaks that appear in the differential scanning calorimetry (DSC) scans in the 500–900 °C range on heating/cooling are related to different phase transformations. The crystal structure of the A24 powders heated up to 900 °C (A24_900 °C) consists of a dual-phase microstructure of Al₂₀Cu₂Mn₃ nanoprecipitates (~28%) and Al matrix (~72%). The sintering of the A24 powders at 500 °C for one hour (A24S) leads to the precipitation of Al₆Mn, Al₂Cu, and the Al₂₀Cu₂Mn₃ T-phase into the Al-enriched matrix. In contrast, the consolidation by SPS (A24SPS) leads to a mixture of an Al solid solution, Al₆Mn, T-phase, and α-Mn with an increased weight fraction of the T-phase and Al₆Mn. The sintered samples exhibit the coexistence of a significant PM/AFM contribution to the M-H curves, with increasing Hc and decreasing EB. A higher microhardness value of about 581 HV is achieved for the A24SPS sample compared to those of the A24 (68 HV) and A24S (80 HV) samples. Full article

The efficient oral delivery of therapeutic proteins and peptides poses a tremendous challenge due to their inherent instability, large molecular size, and susceptibility to enzymatic degradation. Several nanocarrier systems, such as liposomes, solid lipid nanoparticles, and polymeric nanoparticles, have been explored to overcome these problems. Liposomes and other lipid-based nanocarriers show excellent biocompatibility and the ability to encapsulate hydrophobic and hydrophilic drugs; however, they often suffer from poor structural stability, premature leakage of the loaded drugs, and poor encapsulation efficiency for macromolecular peptides and proteins. On the other hand, polymeric nanoparticles are more stable and allow better control over drug release; nevertheless, they usually lack the necessary biocompatibility and cellular uptake efficiency. Recently, lipid-polymer hybrid nanoparticles (LPHNs) have emerged as an advanced solution combining the structural stability of polymers and the biocompatibility and surface functionalities of lipids to enhance the controlled release, stability, and bioavailability of protein and peptide drugs. In this review, an attempt was made to set a clear definition of the LPHNs and extend the concept and area, so to our knowledge, this is the first review that highlights six categories of the LPHNs based on their anatomy. Moreover, this review offers a detailed analysis of LPHN preparation methods, including conventional and nonconventional one-step and two-step processes, nanoprecipitation, microfluidic mixing, and emulsification methods. Moreover, the material attributes and critical process parameters affecting the output of the preparation methods were illustrated with supporting examples to enable researchers to select the suitable preparation method, excipients, and parameters to be manipulated to get the LPHNs with the predetermined quality. The number of reviews focusing on the formulation of peptide/protein pharmaceutics usually focus on a specific drug like insulin. To our knowledge, this is the first review that generally discusses LPHN-based delivery of biopharmaceuticals. by discussing representative examples of previous reports comparing them to a variety of nanocarrier systems to show the potentiality of the LPHNs to deliver peptides and proteins. Moreover, some ideas and suggestions were proposed by the authors to tackle some of the shortcomings highlighted in these studies. By presenting this comprehensive overview of LPHN preparation strategies and critically analyzing literature studies on this topic and pointing out their strong and weak points, this review has shown the gaps and enlightened avenues for future research. Full article

This study systematically investigates the evolution of vacancy-type defects and heterogeneous Cu nanoprecipitates in an Fe₆₀Cr₁₂Mn₈Cu₁₅Mo₃V₂ (at%) multi-principal element alloy during thermal processing, utilizing Positron annihilation lifetime spectroscopy (PAS), coincidence Doppler broadening (CDB) spectroscopy, and transmission electron microscopy (TEM). The results show that the alloy exhibited a dual-phase coexistence structure of Body-Centered Cubic (BCC) and Face-Centered Cubic (FCC). The CDB results show that the density of heterogeneous Cu precipitates gradually increases with annealing temperature. Compared to the as-cast alloy, the precipitates annealed at 773 K exhibit a significantly reduced size (approximately 33 nm) with higher density. The PAS results demonstrate that gradual migration and aggregation of monovacancies at 573 K form vacancy clusters, while contraction and dissociation of these clusters dominate at 673 K. Within the temperature range of 773–973 K, the dynamic equilibrium between the aggregation and decomposition of vacancy clusters maintains stable annihilation characteristics with minimal lifetime changes. Full article

To expand the fundamental understanding of eutectic high-entropy alloys (EHEAs), three novel alloy systems—Cr_1.3Ni₂TiAl, CoCr_1.5NiTi_1.5Al_0.2, and V_0.3CoCr_1.2NiTi_1.1Al_0.2—were rationally designed through synergistic phase diagram analysis and thermodynamic parameter calculations. Comprehensive microstructural characterization coupled with mechanical property evaluation revealed that these alloys possess FCC+BCC dual-phase architectures with atypical irregular eutectic morphologies. Notably, progressive microstructural evolution was observed, including amplified grain boundary density and the emergence of brittle nanoscale precipitates. Mechanical testing demonstrated superior compressive yield strengths in these alloys compared to conventional FCC+BCC EHEAs with ordered eutectic structures, albeit accompanied by reduced fracture strain. The Cr_1.3Ni₂TiAl alloy exhibited optimal ductility, with a maximum fracture strain of 15.6%, while V_0.3CoCr_1.2NiTi_1.1Al_0.2 achieved peak strength, with a compressive yield strength of 1389.5 MPa. Multiscale analysis suggests that the enhanced mechanical performance arises from the synergistic interplay between irregular eutectic configurations, expanded grain boundary area, and precipitation strengthening mechanisms. Full article

Background: Photodynamic therapy (PDT) utilizing nano-based photosensitizers (PSs) offers promising cancer treatment potential but requires rigorous safety evaluation. Conjugated polymer nanoparticles (CPNs) doped with porphyrins, such as platinum porphyrin–doped poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT), exhibit enhanced photodynamic efficiency but lack comprehensive preclinical toxicity data. This study aimed to evaluate the biocompatibility, biodistribution, and acute/subacute toxicity of these CPNs to establish their safety profile for clinical translation. Methods: CPNs were synthesized via nanoprecipitation using amphiphilic stabilizers (PSMA or PS-PEG-COOH) and characterized for colloidal stability in parenteral solutions. Hemolysis assays were used to assess blood compatibility. Single-dose (0.3 and 1 mg/kg, intravenous) and repeated-dose (0.1–1 mg/kg, intraperitoneal, every 48 h for 28 days) toxicity studies were conducted in BALB/c mice. Hematological, biochemical, histopathological, and biodistribution analyses (via ICP-MS) were performed to evaluate systemic and organ-specific effects. Results: CPNs demonstrated excellent colloidal stability in 5% dextrose, with minimal aggregation. No hemolytic activity was observed at concentrations up to 50 mg/L. Single and repeated administrations revealed no significant changes in body/organ weights, hematological parameters (except transient fibrinogen elevation), or liver/kidney function markers (ALT, AST, BUN, Cr). Histopathology showed preserved tissue architecture in major organs, with mild hepatocyte vacuolation at 30 days. Biodistribution indicated hepatic/splenic accumulation and rapid blood clearance, suggesting hepatobiliary elimination. Conclusions: Platinum porphyrin–doped F8BT CPNs exhibited minimal acute and subacute toxicity, favorable biocompatibility, and no systemic adverse effects in murine models. These findings support their potential as safe PS candidates for PDT. However, chronic toxicity studies are warranted to address long-term organ accumulation and metabolic impacts. This preclinical evaluation provides a critical foundation for advancing CPNs toward clinical applications in oncology. Full article

To enhance the mechanical properties of 6063-T4 aluminum alloy tubes, surface mechanical grinding treatment was conducted under graphene-assisted lubrication. The effects of rotational speed and cooling conditions on the mechanical properties of aluminum alloy tubes under biaxial stress were systematically explored. It was found that increasing the rotational speed and cooling rate facilitates the formation of finer lamellar grains, higher-density nano-precipitates, and a reduced dislocation density on the tube surface. These microstructural characteristics significantly contribute to an increased yield strength and sustained strain hardening capacity during bulging deformation. This study proposes an innovative approach for improving the strength and toughness of light alloy components during integral forming, providing meaningful insights for future engineering applications. Full article

Nano-precipitates play a vital role in the development of ultra-high strength steels (UHSSs). In recent decades, the B2-NiAl phase, which forms highly coherent interfaces with the BCC-Fe matrix, has attracted significant attention for enhancing the strength of UHSSs. However, direct experimental investigation of alloying elements—specifically their atomic distribution and the resulting effects on the interfacial bonding strength of nano-precipitates—remains challenging. This study uses density functional theory (DFT)-based first-principles calculations to investigate the role of alloying elements in modifying interfacial characteristics. Six elements—Al, Ni, Co, Cr, Mo, and C—are introduced at various occupation sites within the coherent interface model to calculate the formation energy. The predicted preferential distribution of solid-solution atoms aligns well with experimental findings. Stable configurations of alloying segregation are selected for first-principles rigid tensile fracture tests along the <001> direction. Electronic structure analysis reveals that Co, Cr, and Mo segregation enhances interface strength due to solute-induced high charge density and the preservation of bonding characteristics of bulk phases at the interface. The results offer valuable insights and practical guidance for developing novel ultrahigh-strength structural steels strengthened by B2-NiAl. Full article

The interface between dispersed compound nanoprecipitates and metal substrates can act as effective hydrogen traps, impeding hydrogen diffusion and accumulation, thus mitigating the risk of hydrogen embrittlement and hydrogen-induced coating failure. In this study, we considered the precipitation of vanadium carbide (VC) and vanadium nitride (VN) nanoprecipitates on a body-centered cubic Fe (α-Fe) substrate in the Kurdjumov–Sachs (K–S) orientation relationship. To evaluate the stability and hydrogen trapping ability of the interface, we used the first-principles method to calculate the interfacial binding energy and hydrogen solution energy. The results show that the stability of the interface was related to the type and length of bonding between atoms at the interface. The interface zone and the interface-like Fe zone have the best hydrogen trapping effect. We found that hydrogen adsorption strength depends on both the Voronoi volume and the number of coordinating atoms. A larger Voronoi volume and smaller coordination number are beneficial for hydrogen capture. When a single vacancy exists around the interface region, the harder it is to form a vacancy, and the more unstable the interface becomes. In addition to the C vacancy at the Baker–Nutting relationship interface found in previous studies being a deep hydrogen trap, the Fe and V vacancies at the α-Fe/VC interface and the V and N vacancies at the α-Fe/VN interface in the K–S relationship also show deep hydrogen capture ability. Full article

The formation of nano-sized Hf₂Fe precipitates at grain boundaries through Fe micro-alloying enhances the strength of Ti-Zr-Hf-Nb-Ta multi-principal element alloys (MPEAs), but this improvement comes at the cost of reduced ductility. Aging at 500 °C for just 30 min resulted in a marked reduction in elongation, from 17.5% to 7.5%. This decline is attributed to lattice mismatch between the precipitates and the matrix, as well as increased stacking stress at the grain boundaries. By adjusting the Fe composition and heat treatment parameters, the quantity of Hf₂Fe at the grain boundaries of (TiZrHfNbTa)_100−xFe_x alloy was effectively controlled, achieving a balanced combination of strength of 1037 MPa and elongation of 14%. Furthermore, this method enabled ductility modulation over a wide range, with elongation varying from 2.65% to 19% while maintaining alloy strength between 955 and 1081 MPa, providing valuable insights for tailoring these alloys to diverse application requirements. The precipitation thermodynamics of the (TiZrHfNbTa)_100−xFe_x alloy was also investigated using the CALPHAD method, with thermodynamic calculations validated against experimental results, laying a foundation for more in-depth kinetic study of nano-size precipitates in these alloys. Additionally, the relationships between thermodynamics, precipitates evolution, and mechanical properties were discussed. Full article

Background/Objectives: HIV persists in central nervous system (CNS) reservoirs, where infected microglia and macrophages drive neuroinflammation, oxidative stress, and neuronal damage, contributing to HIV-associated neurocognitive disorder (HAND). Nanoparticle-based drug delivery systems, particularly poly(lactic-co-glycolic acid) (PLGA) nanoparticles, offer a promising strategy to improve CNS antiretroviral therapy (ART) delivery. This study aimed to evaluate the efficacy of co-administration of PLGA nanoparticles (NPs) encapsulating elvitegravir (EVG) and curcumin (CUR) in targeting CNS reservoirs, reducing neuroinflammation, and mitigating oxidative stress. Methods: PLGA NPs encapsulating EVG and CUR (PLGA-EVG and PLGA-CUR) were prepared via the nanoprecipitation method. The NPs were characterized for size, zeta potential, and encapsulation efficiency (EE). Their therapeutic efficacy was evaluated in vitro using U1 macrophages and in vivo in Balb/c mice. Key parameters, including cytokine levels, oxidative stress markers, and neuronal marker expression, were analyzed. Results: The PLGA-EVG and PLGA-CUR NPs demonstrated high EE% (~90.63 ± 4.21 for EVG and 87.59 ± 3.42 for CUR) and sizes under 140 nm, ensuring blood–brain barrier (BBB) permeability. In vitro studies showed enhanced intracellular EVG concentrations and reductions in proinflammatory cytokines (IL-1β, TNFα, and IL-18) and improved antioxidant capacity in U1 macrophages. In vivo, the co-administration of NPs improved CNS drug delivery, reduced neuroinflammation and oxidative stress, and preserved neuronal markers (L1CAM, synaptophysin, NeuN, GFAP). Conclusions: PLGA-based co-delivery of EVG and CUR enhances ART CNS drug delivery, mitigating neuroinflammation and reducing oxidative stress. These findings highlight the potential of nanoparticle-based ART strategies to address limitations in current regimens and pave the way for more effective HAND therapies. Future studies should focus on optimizing formulations and evaluating safety in chronic HIV settings. Full article