Search Results (1,264)

Lipid-based nanoparticles are widely explored as non-viral vectors for nucleic acid delivery, where the molecular structure of cationic lipids strongly determines their performance. Five-membered heterocyclic linkers were explored as a new structural motif in cationic amphiphilic lipids for the development of promising gene delivery candidates. Novel lipids incorporating pyrrole, furan, and thiophene linkers were synthesized alongside structurally related aliphatic analogues, enabling systematic evaluation of how linker type influences physicochemical behavior and self-assembly properties. Self-assembly behavior in aqueous media was characterized by dynamic light scattering, and pDNA encapsulation efficiency was measured using the Quant-iT Pico-Green method. The resulting liposomes exhibited hydrodynamic diameters ranging from 92 to 1317 nm, while corresponding lipoplexes ranged from 302 to 1159 nm. Amphiphiles containing heterocyclic linkers demonstrated high pDNA encapsulation (>80% at optimal N/P ratios), whereas aliphatic analogues showed significantly reduced performance. These results demonstrate that linker structure strongly influences both self-assembly and nucleic acid binding properties. By evaluating structure–activity relationships, five-membered heterocycles are proposed as promising structural elements for the rational development of lipid-based gene delivery candidates. Full article

Everolimus is approved for the treatment of advanced renal cell carcinoma after VEGF-targeted therapy, metastatic HR-positive/HER2-negative breast cancer in combination with exemestane, and other oncologic indications. However, an intravenous option has not been developed, largely due to its pronounced hydrophobicity and limited oral bioavailability of approximately 15–20%. In this study, we report the development of Sapu003, a novel intravenous Everolimus7 formulation enabled through the Deciparticle™ platform. A diverse library of mPEG-based block copolymers was evaluated for their ability to encapsulate Everolimus and self-assemble into stable nanoparticle structures. mPEG-Chol was ultimately selected based on its favorable biocompatibility characteristics. In addition to Everolimus, mPEG-Chol and related analogs demonstrated broad formulation compatibility with multiple hydrophobic therapeutics, including Sirolimus, Tacrolimus, Cyclosporine, as well as representative peptides and polyketides. Clinical manufacturing was conducted in a cGMP environment over a 7-day production cycle. Production was carried out under amber light using light-protective vials to reduce drug degradation. The bulk material was sterile-filtered, and subsequent fill/finish/lyophilization operations were performed under temperature-controlled conditions with high precision in fill accuracy (≥98%). After reconstitution, the final product yielding uniform Deciparticles™ that met predefined sterility and particle size criteria. Stability studies demonstrated that the formulation remained stable for at least one month at 5 °C and retained acceptable in-use stability for at least 24 h at room temperature. The process was successfully scaled beyond 10 g, supporting an ongoing Phase 1b open-label dose escalation clinical study of Sapu003 in combination with exemestane in patients with advanced mTOR-sensitive solid tumors (NCT07369505). In vivo evaluation demonstrated strong antitumor efficacy following intravenous administration (QW × 3), with tumor growth inhibition reaching 97–98% in the U-87MG glioblastoma xenograft model. No evidence of phlebitis was observed with repeated tail vein dosing. In this model, Sapu003 dosed weekly showed superior tumor suppression compared with oral Everolimus. Collectively, screening of a mPEG-block copolymer library identified mPEG-Chol as a lead excipient capable of consistently forming stable Deciparticles™ with sub-20 nm mean particle size. The resulting intravenous Everolimus formulation demonstrated scalable manufacturing, favorable stability, and potent antitumor activity in preclinical models, supporting further clinical evaluation of Sapu003 in advanced solid tumors. Full article

Objectives: This study aimed to develop curcumin nanoparticles (Cur@PCL-PEG-MF/cRGDfc) with retinal-targeting capability and to evaluate their biological effects and pharmacological mechanisms in vitro. Methods: After synthesis of the carrier framework, metformin (MF) and cRGDfc were conjugated to the carrier material using the carbodiimide method and Michael addition reaction, respectively. Subsequently, self-assembled nanoparticles were formed from the carrier and curcumin under specific conditions. The materials were characterized by spectroscopy, chromatography, elemental analysis, energy-dispersive spectroscopy and X-ray diffraction. The efficacy of the formulation was evaluated in two cell lines, ARPE-19 and HUVEC-T1. In addition, the pharmacological mechanism was explored using transcriptome sequencing as a complementary approach. Key Findings: Self-assembled nanoparticles were successfully prepared by combining the two modified carrier materials, PCL-PEG-MF and PCL-PEG-cRGDfc, with curcumin. The nanoparticles exhibited an encapsulation efficiency of 78.09%, a particle size of 162.33 nm, and a zeta potential of −23.28 mV and displayed a spherical morphology. They showed sustained release in simulated physiological conditions and stronger affinity for ARPE-19 cells under oxidative stress. Nearly 100% of the nanoparticles were internalized by the cells, which was accompanied by reduced ROS and LDH release and decreased DNA fragmentation. In addition, the nanoparticles inhibited neovascularization by reducing VEGF-A release, thereby potentially protecting the retina in macular degeneration and reducing choroidal hemorrhage. Further analyses showed that curcumin and its nanoformulations significantly reduced the expression of inflammatory factors such as IL-1β and IL-18, lowered the protein levels of Caspase-1, GSDMD-N, and NLRP3, and increased AMPK levels. Conclusions: Using PCL-PEG as the carrier framework, MF and cRGDfc were conjugated to construct a curcumin-loaded nanoparticle with retinal-targeting capability. This nanoparticle, characterized by a small particle size, sustained release, and targeted delivery to retinal pigment epithelium (RPE) cells under oxidative stress, alleviated oxidative stress-induced damage. Its therapeutic effect may be mediated, at least in part, by interference with the AMPK/mTOR pathway and activation of the NLRP3/Caspase-1/GSDMD pathway. Full article

Pt-based catalysts remain the premier hydrogen evolution reaction (HER) electrocatalysts for anion-exchange membrane water electrolyzers. Faced with insufficient abundance and high cost, developing low-Pt electrocatalysts that can accelerate the Volmer step while maintaining high durability is critically important yet challenging. Herein, we propose niobium nitrides with excellent conductivity and stability as supports for Pt to enhance the alkaline HER. A polyoxoniobate-based molecular self-assembly strategy was ingeniously designed to fabricate Nb₄N₅ nanospheres, on which ultrafine Pt nanoparticles (NPs) were successfully immobilized, forming Pt/Nb₄N₅ heterostructures (denoted as Pt/Nb₄N₅). The rich interface structures with metal–support interactions drive charge transfer from Pt to Nb₄N₅, which modulates the electronic structure of Pt and Nb sites, collectively lowering interfacial charge transfer resistance, generating abundant active sites, and improving catalyst durability. Consequently, the Pt/Nb₄N₅ catalyst achieves exceptional HER performance, including a low overpotential (22 mV@10 mA cm⁻²), a small Tafel slope (26 mV dec⁻¹), an 11.5-fold higher mass activity at 150 mV, and remarkable durability, drastically surpassing the commercial Pt/C catalyst. Notably, the Pt/Nb₄N₅-based electrolyzer requires only 1.508 V to drive 10 mA cm⁻². This work offers a viable pathway to engineer highly active and durable low-Pt electrocatalysts for energy-related applications. Full article

Nanotheranostics integrate theranostic functions onto a single nanoscale platform, and have become a new approach in precision medicine. Nanotheranostics rely on probes. However, traditional fluorescent probes often exhibit aggregation-caused quenching (ACQ) when loaded at high concentrations onto nanocarriers, severely limiting their imaging performance. Aggregation-induced emission agents (AIEgens) offer a solution to this long-standing problem through their ability to enhance fluorescence during aggregation. This mini-review systematically outlines nanotheranostic systems based on aggregation-induced emission (AIE). We first introduce the basic mechanism of AIE (the limitation of molecular internal motion) and its advantages over traditional fluorescent probes. Then, we discuss the design strategies of AIE nanoprobes according to the types of nanocarriers (including liposomes, polymer nanoparticles, and self-assembling systems). Additionally, we emphasize the disease-specific AIE nanotheranostic designs tailored for pathological microenvironments such as tumors, neurodegenerative diseases, and inflammatory diseases. Finally, we conduct an in-depth analysis of the current challenges hindering clinical translation, and propose future AIE nanotheranostic technologies applicable to clinical practice and the direction for personalized medicine. Full article

Background/Objectives: Natural macromolecule-based drug delivery carriers have gained extensive attention for biomedical applications. This study aimed to construct an efficient oral delivery system for the widely used antitumor drug docetaxel (DTX) by utilizing natural nanoparticles derived from Ganoderma (LZ-Nnps). Methods: LZ-Nnps loaded with DTX (LZ-Nnps-DTX) were fabricated via an optimized heat-induced self-assembly approach and characterized for morphology, particle size, zeta potential, stability, drug loading, encapsulation efficiency, and molecular interactions with DTX. Intestinal absorption, pharmacokinetics, and tissue distribution were respectively assessed, while antitumor efficacy, macrophage internalization mechanisms, and immunomodulatory activation were further investigated. Results: The optimized formulation showed a particle size of 361.3 ± 5.3 nm, zeta potential of −39.55 ± 1.31 mV, drug loading of 1.51 ± 0.08%, and near-complete encapsulation efficiency (99.97 ± 0.02%), with favorable stability in gastrointestinal fluids. Hydrogen bonding and hydrophobic interactions effectively kept DTX in a stable amorphous state. LZ-Nnps-DTX markedly improved DTX aqueous solubility, dissolution, and intestinal absorption. In vivo assays showed oral LZ-Nnps-DTX achieved 34-fold higher C_max and 7.8-fold larger plasma AUC_0-t than free DTX, and mainly accumulated in the liver and lung. The nanoparticles entered Caco-2 cells via macropinocytosis and mainly accumulated in the liver. LZ-Nnps-DTX exerted strong cytotoxicity against HepG2, A549, and HCT116 cells, was internalized by RAW264.7 macrophages through caveolae-mediated endocytosis and phagocytosis, and stimulated TNF-α and NO production to suppress tumor growth. Conclusions: These findings demonstrate that LZ-Nnps-DTX effectively enhances oral bioavailability, exerts potent antitumor effects, and activates macrophage-mediated immunity, supporting its promise as an oral DTX delivery system. Full article

Nanoporous films assembled by low-kinetic-energy deposition of individual nanoparticles are complex nanomaterials for a variety of applications, from gas sensing to neuromorphic computing. We develop a numerical strategy for assembling metallic nanoparticles into 25–40 nm thick films from an arbitrary distribution of Au nanoparticles in terms of their initial size and shape. We characterize the structural properties of the assembled films as a function of the initial nanoparticle distribution. The morphology of the deposited nanoparticles affects nanofilm thickness, porosity, and its internal structure, including the length, type, and density of dislocations. Film porosity and the average dislocation length mainly correlate with the size of deposited nanoparticles. At the same time, thickness and dislocation density can also be affected by the shape of the larger nanoparticles deposited. Full article

Lipid nanoparticles (LNPs) have emerged as popular nucleic acid delivery systems, yet the dynamic mechanisms related to their self-assembly and structural maturation remain insufficiently understood due to the limitations of traditional offline characterization tools. This study establishes a time-resolved (TR) in situ small-angle X-ray scattering (SAXS) methodology to monitor the structural evolution of LNPs during microfluidic formulation and subsequent maturation. By integrating a dual-channel microfluidic mixing system with a SAXS measurement platform, we successfully captured the real-time scattering profiles of both empty and messenger RNA-loaded nanoparticles (mRNA-LNPs). The results demonstrate distinct assembly pathways for empty-LNPs and those encapsulated with mRNA. The empty-LNPs undergo a gradual transition toward periodic nanostructures, whereas mRNA-LNPs exhibit rapid complexation into stable subunits followed by hierarchical assembly. Furthermore, the platform effectively tracked nanoscale structural rearrangements during a microfluidic dilution process, revealed by subtle shifts in scattering peaks and internal periodicity. Overall, this time-resolved approach provides a robust experimental framework for capturing transient intermediate states, offering a valuable tool to elucidate molecular assembly mechanisms and facilitate the rational design of next-generation nanomedicines. Full article

As a naturally self-assembling protein nanocarrier, ferritin enables multivalent antigen display and functions as an intrinsic adjuvant to enhance vaccine-induced immune responses. Streptococcus equi subsp. equi (S. equi) is the causative agent of equine strangles, an acute and highly contagious respiratory disease responsible for substantial economic losses worldwide. However, currently available vaccines often show suboptimal immunogenicity and limited protective efficacy. In this study, we developed a recombinant equine ferritin (rHF)-based nanoparticle vaccine, rSE5Mix, presenting five core protective antigens (EQ8, EQ5, CNE, IdeE, EAG). The fusion proteins efficiently assembled into uniform nanoparticles. Immunization of BALB/c mice elicited rapid, high-titer antigen-specific IgG antibodies and a balanced Th1/Th2 immune response without additional adjuvants. Following lethal challenge with S. equi, rSE5Mix-immunized mice showed 100% survival and markedly milder clinical signs. Histopathological analysis demonstrated significantly alleviated organ damage, and bacterial loads in major tissues were reduced to nearly undetectable levels. Importantly, compared with the octavalent tandem vaccine rSE8, rSE5Mix induced faster elevation of partial antigen-specific antibodies, especially for EQ8 and CNE. Their antibody titers were comparable at later stages. This study developed a safe and effective ferritin nanoparticle vaccine candidate against equine strangles and verified that equine ferritin is a promising candidate delivery platform for veterinary bacterial vaccines. Full article

Objective: Self-assembled nanoparticles (SANs) naturally occurring in Traditional Chinese Medicine (TCM) decoctions are promising drug carriers due to their biocompatibility, but uncontrolled assembly often leads to poor stability, limiting transdermal permeability and industrial application. This study aimed to fabricate stable and uniform SANs from licorice by precisely regulating the controlled nanoprecipitation of its water- and alcohol-extracted components. The transdermal delivery efficiency and therapeutic efficacy of the SANs in the treatment of atopic dermatitis (AD) were evaluated. Methods: Licorice self-assembled nanoparticles (LD-SANs) were prepared by mixing water and ethanol extracts of licorice, followed by ethanol evaporation under reduced pressure to trigger nanoprecipitation. In vitro transdermal tests compared the delivery efficiency of six major bioactive compounds between LD-SANs and traditional licorice decoction (LD). The penetration mechanism was investigated via passive diffusion and cellular uptake studies. In an AD mouse model, the therapeutic effects and expression of tight junction (TJ) proteins (Occludin and Claudin-1) were assessed. Results: The average particle size of LD-SANs is 200 nm, and it is uniform and stable. LD-SANs significantly enhanced the delivery efficiency of all six bioactive compounds compared to LD. Mechanistic studies revealed a unique “dual-channel” penetration mechanism: the nanoscale size enabled passive diffusion through hair follicles, intercorneocyte lipid gaps, and skin appendages, while perifollicular antigen-presenting cells (APCs) actively recognized and internalized the nanoparticles, creating a cell-mediated active targeting route that collectively boosted skin accumulation. In the AD model, LD-SANs promoted the expression of Occludin and Claudin-1 in the epidermal granular layer, reinforcing intercellular barrier integrity. Conclusions: By combining “efficient penetration” and “barrier repair”, LD-SANs demonstrated notable therapeutic efficacy in AD. This work transforms a traditional decoction into a well-characterized, high-performance nanomedicine and offers a novel strategy for developing TCM-based transdermal delivery systems. Full article

Fatty acids (FAs) have drawn attention in the field of oncology due to their multifaceted role, not only as structural components of lipid-based delivery systems but also as functional moieties that can enhance the pharmacokinetic and biological behavior of anticancer drugs and, subsequently, their therapeutic performance. Due to their biocompatibility, structural diversity, high affinity for biological membranes, and albumin-binding capacity, FAs can increase drug lipophilicity, membrane permeability, systemic distribution, tissue distribution, and enable controlled enzymatic release. All these properties endorse the development of nanocarriers containing FAs, such as liposomes, lipid nanoparticles (LNPs), self-nanoemulsifying drug delivery systems (SNEDDS), and self-assembling lipidic prodrugs (LAPs). In addition, several FAs, especially polyunsaturated FAs, seem to have a direct anticancer activity by modulating lipid metabolism, oxidative stress, membrane organization, and regulating cell death pathways. This review summarizes the FA conjugation chemistry, the influence of FA on the pharmacokinetics and tumor-targeting capacity of anticancer agents, and the current developments in FA-based cancer treatment strategies, while also covering the biological functions of FA in cell death pathways and cancer metabolism. By integrating medicinal chemistry, nanocarrier design, pharmacokinetic modulation, and tumor lipid biology, this review positions FA-based strategies as a relevant and evolving platform for improving anticancer drug delivery, tumor selectivity, and therapeutic performance. Full article

(1) Background: Cerium silicate (CeSi) nanoparticles (NPs) have potential as a restorative filler particle with multifunctional properties to improve longevity. To increase the biological activity, these nanoparticles can be fabricated with ultrasmall pores (mesoporous) (MPCeSi-NP) that can be loaded with a polyphosphate inhibitor, such as gallein. (2) Methods: MPCeSi-NPs were custom-synthesized with a microemulsion method, using cetyltrimethylammonium bromide (CTAB) as a template for self-assembly. Biocompatibility with oral keratinocytes/fibroblasts was tested, with the addition of examining the biomineralization potential with human bone-marrow-derived mesenchymal stromal cells (BM-MSCs). MPCeSi-NP, loaded with gallein, was tested against Rothia dentocariosa (Rd). MPCeSi-NP was added to a resin matrix of triethylene glycol dimethacrylate (TEGDMA) and Bisphenol A-glycidyl methacrylate (BisGMA) with subsequent mechanical properties evaluation. (3) Results: MPCeSi-NPs had high biocompatibility with oral keratinocytes and fibroblasts, especially at concentrations below 300 µg/mL. MPCeSi-NPs induced the biomineralization of BM-MSCs. Higher cerium levels increased mineralization. MPCeSi-NP had weak antimicrobial activity against Rd. At 1% wt, MPCeSi-NPs did not reduce the polymerization potential and mechanical properties of a TEGDMA:BisGMA polymer material, with controlled release of gallein in a simulated degradation model. (4) Conclusions: MPCeSi-NPs are highly biocompatible and bioinductive and have the potential to improve the biological response of current restorative materials. Full article

A study was conducted on the construction of sulfonated poly(aryl ether ketone) nanomicelles and their dispersion–displacement synergistic behavior in deep oil recovery. Unlike conventional surfactant systems, inorganic nanoparticle-based EOR materials, and polymeric nanofluids that mainly rely on interfacial tension reduction, wettability alteration, or viscosity regulation, this study constructs self-assembled sulfonated poly(aryl ether ketone) nanomicelles that integrate a rigid aromatic backbone, ionizable sulfonic acid groups, nanoscale dispersion, and interfacial regulation within one polymeric architecture. Sulfonated poly(aryl ether ketone) nanomicelles were prepared by combining polymer sulfonation with solvent-induced self-assembly, and their structural features, dispersion stability, interfacial behavior, porous-media transport, and displacement performance were systematically evaluated. Spectroscopic characterization confirmed the successful introduction of sulfonic acid groups into the polymer backbone. The resulting nanomicelles exhibited an average hydrodynamic diameter of 117.8 nm, a polydispersity index of 0.186, and a zeta potential of −38.6 mV in deionized water, while a value of −27.4 mV was still maintained at a salinity of 150,000 mg/L, indicating good electrostatic stability under highly mineralized conditions. Further evaluation showed that the 0.30 wt% system retained a transmittance of 97.4% after 15 d of static standing, and its particle size remained at 151.7 nm even under 120 °C and 150,000 mg/L, demonstrating favorable thermal–salinity tolerance. At the same concentration, the oil–water interfacial tension decreased to 6.9 mN/m at 1800 s, while the contact angle of oil-aged quartz was reduced from 118.4° to 58.7°, indicating effective regulation of both the oil–water interface and the solid surface wettability. During microscopic displacement, the residual oil area fraction decreased from 32.8% after water flooding to 14.6%, and cluster-like oil, corner oil, and film-like oil were reduced from 14.6%, 9.8%, and 8.4% to 5.9%, 4.2%, and 4.5%, respectively. In core flooding, the incremental oil recovery reached 13.2%, the final water cut decreased to 81.2%, and the injection pressure increased only from 0.42 MPa to 0.68 MPa. These results indicate that sulfonated poly(aryl ether ketone) nanomicelles promote deep residual-oil mobilization through the combined effects of stable dispersion, interfacial regulation, and effective transport, with 0.30 wt% identified as the preferred concentration range. The main scientific contribution of this work is to establish a structure–dispersion–interface–transport–displacement relationship for SPAEK nanomicelles under deep-reservoir conditions, providing a polymeric nanomicelle-based strategy distinct from conventional surfactant, sulfonated polymer, and nanoparticle flooding systems. Full article

C-reactive protein (CRP) is one of the most essential biomarkers for the early detection of inflammation and infection. In this study, we developed a sensitive and selective electrochemical immunosensor for CRP detection, leveraging the unique properties of gold nanoparticles (AuNPs). A nanostructured layer of AuNPs was deposited onto a screen-printed carbon electrode (SPCE), followed by the formation of a self-assembled monolayer (SAM) of L-cysteine and EDC/sulfo-NHS chemistry. The antibody was covalently immobilized onto the modified electrode through optimized dual-crosslinking chemistry. Detection conditions were systematically optimized, with pH 8.0 in Tris buffer providing the best electrochemical response. Electrochemical characterization was performed using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV) in a 5 mM K₃[Fe(CN)₆]/K₄[Fe(CN)₆] redox probe solution containing 0.1 M KCl. CRP detection was achieved by monitoring the increase in charge transfer resistance (Rct) upon specific binding of the target CRP antigen to the immobilized antibody. Spiked recovery experiments showed spiked recovery rates ranging from 98.01% to 107.14%, with a standard deviation below 4%. Regeneration studies demonstrated high efficiency, confirming the suitability of the sensor interface for repeated and reliable measurements. Under optimized conditions, the immunosensor exhibited excellent analytical performance, including a low limit of detection (LOD) of 0.16 µg/mL, a wide linear detection range of 5–100 µg/mL, high selectivity against 13 potential interferents (including inflammatory cytokines), and good reproducibility with a relative standard deviation (RSD) of 3.69%. The sensor also showed strong stability, retaining more than 95% of its signal after 15 days, and high regeneration efficiency of 97% over seven cycles. These results highlight the strong potential of the proposed immunosensor for point-of-care (POC) applications due to its simple fabrication, cost-effectiveness, user accessibility, and robust analytical performance. Full article

Gold and silver nanoparticles have attracted extensive attention in SERS detection due to their excellent plasmonic properties. In this study, a high-performance SERS substrate was successfully prepared by a liquid–liquid self-assembly strategy. Driven by the Marangoni effect, Au-Ag nanoparticles spontaneously form a uniform and dense monolayer structure on the silicon wafer, constructing an efficient plasmon “hotspot” region, which significantly improves the detection sensitivity of the substrate. The performance of the SERS substrate was systematically evaluated using CV and Me B as Raman probe molecules. The results show that the substrate exhibits an excellent enhancement effect and good SERS sensitivity for both probe molecules. The characteristic vibration peak can be clearly identified, and the detection limit (LOD) of crystal violet is 6.76 × 10⁻¹¹ M. The substrate was applied to detect thiram residues in lake water with a LOD of 1.084 × 10⁻⁷ M, achieving highly sensitive detection. This study shows that Au-Ag nanoparticles deposited on silicon wafers by liquid–liquid self-assembly strategy can be used as a high-performance SERS substrate. It can be used for rapid and sensitive detection of thiram pesticide residues in water, and provides an efficient and feasible analysis tool for water environment safety monitoring. Full article