Search Results (45)

Conventional therapies for rheumatoid arthritis (RA) are limited by poor selectivity, insufficient modulation of the oxidative inflammatory microenvironment, and systemic side effects. Oxidative stress and macrophage-driven immune dysregulation represent critical therapeutic targets. Cinnamaldehyde (CA) and arginine (Arg) possess antioxidant, anti-inflammatory, and anti-osteoclastogenic activities, but their poor solubility, instability, and lack of targeting restrict clinical application. Here, we report a pH-responsive cinnamaldehyde–arginine nanoprodrug (Arg-CA NPs), synthesized via Schiff base reaction, that spontaneously self-assembles into uniform nanoparticles capable of acid-triggered dual-drug release. Arg-CA NPs enhanced the solubility and stability of CA, exhibited excellent dispersibility and circulatory stability, and demonstrated intrinsic antioxidant and anti-inflammatory properties. Mechanistically, Arg-CA NPs attenuated intracellular ROS accumulation, preserved mitochondrial function, and reprogrammed macrophages toward an anti-inflammatory M2 phenotype by suppressing hypoxia-inducible factor-1α (HIF-1α), cyclooxygenase-2 (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. In an adjuvant-induced arthritis (AIA) rat model, Arg-CA NPs selectively accumulated in inflamed joints and significantly alleviated joint swelling, synovial inflammation, cartilage erosion, and bone destruction. These findings identify Arg-CA NPs as a promising redox-active nanoplatform for RA therapy by targeting oxidative stress and immune dysregulation. Full article

Background/Objectives: The aim of the present study was to conduct a systematic in vitro assessment of the biofunctionalities of newly synthesized lignin (LNPs) and lignin–chitosan nanoparticles (LCNPs) via a comparative in vitro estimation of their cytotoxicity, cytocompatability potential, radical-scavenging activity, and antimicrobial performance, thereby establishing a benchmark for their sustainable design and biomedical applications. Methods: LNPs and LCNPs were synthesized via “green” self-assembly and co-assembly methods. Results: In vitro cytotoxicity studies on L929 fibroblasts and HaCaT keratinocytes demonstrated higher long-term viability for LCNPs (half-maximal inhibitory concentration IC₅₀ = 3.05 mg/mL at 72 h) compared with LNPs (IC₅₀ = 1.37 mg/mL), while both formulations maintained >76% viability at a concentration of 0.5 mg/mL. Electron Paramagnetic Resonance (EPR) and spectrophotometric antioxidant assays displayed strong radical scavenging activity, with LNPs excelling in ^●OH, NO, and ABTS scavenging and LCNPs exhibiting enhanced lipid peroxidation and superoxide inhibition potential. Antimicrobial testing revealed minimal inhibitory concentration (MIC) reductions of the nanoparticles up to 8–13-fold compared to lignin solutions, with LCNPs showing higher activity against Gram-positive and Gram-negative microbial strains. Conclusions: These results highlight LCNPs as biocompatible, antioxidant, and antimicrobial nanoplatforms with potential for regenerative medicine, oxidative stress mitigation, and infection control. Full article

Tea polyphenols (TPs) are promising natural bioactive compounds; however, their practical application is hindered by poor stability and low bioavailability. To address this challenge, we synthesized TP–iron nanoparticles (TP-Fe NPs) through coordination-driven self-assembly. Comprehensive characterization (SEM, TEM, FTIR, and XRD) confirmed the successful formation of stable TP-Fe NPs, primarily mediated by phenolic hydroxyl and carbonyl groups. Among TP-Fe NPs, the TP3-Fe1 NPs exhibited superior performance, achieving DPPH and ABTS radical scavenging rates of 65.71% and 89.64%, respectively, and inhibition rates of 91.44% against E. coli and 88.67% against S. aureus. Furthermore, TP3-Fe1 NPs demonstrated excellent biocompatibility, showing no significant cytotoxicity to L929 cells at 0.01–0.1 mg/mL. These findings highlight the potential of TP3-Fe1 NPs as a safe and effective material with dual functionality for antioxidant and antibacterial applications. Full article

Developing natural lipid-based conjugates/prodrugs has emerged as a promising topic in pharmaceutical chemistry and biomedicine. In this work, a natural antioxidant lipid, α-tocopherol (vitamin E), was covalently connected with doxorubicin (Dox) to synthesize a Toco–Dox conjugate through two approaches: triphosgene activation (method A) and 4-nitrophenyl chloroformate activation (method B). The latter method is non-volatile and generates safe-to-handle byproduct 4-nitrophenol, making it much less hazardous and more eco-friendly. The molecular structure of Toco–Dox was characterized by ¹H, ¹³C NMR, FT-IR, and MALDI-TOF-MS. Toco–Dox could self-assemble into nanoparticles in the DMSO/water mixture and Toco–Dox nanoparticles were further characterized by DLS. Moreover, the molecular properties of Toco–Dox were theoretically calculated or virtually analyzed (Dox as a control). In addition, unlike (free) Dox, Toco–Dox showed moderate MCF-7 breast cancer cell inhibition (cytotoxicity) and a cytoplasm localization behavior. This work provided an efficient approach to develop a natural (fat-soluble) vitamin-based prodrug system for breast cancer chemotherapy. Full article

Treating brain cancer remains challenging due to the blood–brain barrier (BBB) and the systemic toxicity of chemotherapy. This study focuses on developing human serum albumin (HSA) nanoparticles modified with low-molecular-weight protamine (LMWP) to improve crossing the BBB and enable targeted delivery of curcumin and temozolomide (TMZ). Nanoparticle stability was enhanced by crosslinking with aldehyde groups from oxidized gellan (OG). The successful attachment of LMWP to HSA at the thiol group of Cys34 was confirmed through FT-IR and ¹H-NMR analyses. Most self-assembled nanoparticles were smaller than 200 nm in diameter. Curcumin showed higher encapsulation efficiency than TMZ. In vitro drug release was pH-dependent: curcumin released more at pH 7.4, while TMZ release was better at pH 4. Higher crosslinking degrees reduced drug release. Cytotoxicity assays on V79-4 (normal) and C6 (glioma) cell lines showed increased apoptosis and significantly lower IC₅₀ values for co-encapsulated formulations, indicating a synergistic effect. Curcumin’s antioxidant activity was maintained and protected from UV degradation by the polymer matrix. The parallel artificial membrane permeability assay (PAMPA) confirmed that the functionalized formulations with co-encapsulated drugs could cross the BBB. Hemocompatibility studies indicated a favorable profile for intravenous use. Full article

Nanogels are polymer-based, crosslinked hydrogel particles on the nanometer scale. Nanogels developed from synthetic and natural polymers have gathered a great deal of attention in industry and scientific society due to having an increased surface area, softness, flexibility, absorption, and drug loading ability, as well as their mimicking the environment of a tissue. Nanogels having biocompatibility, nontoxic and biodegradable properties with exceptional design, fabrication, and coating facilities may be used for a variety of different biomedical applications, such as drug delivery and therapy, tissue engineering, and bioimaging. Nanogels fabricated by chemical crosslinking and physical self-assembly displayed the ability to encapsulate therapeutics, including hydrophobic, hydrophilic, and small molecules, proteins, peptides, RNA and DNA sequences, and even ultrasmall nanoparticles within their three-dimensional polymer networks. One of the many drug delivery methods being investigated as a practical option for targeted delivery of drugs for cancer treatment is nanogels. The delivery of DNA and anticancer drugs like doxorubicin, epirubicin, and paclitaxel has been eased by polymeric nanogels. Stimuli-responsive PEGylated nanogels have been reported as smart nanomedicines for cancer diagnostics and therapy. Another promising biomedical application of nanogels is wound healing. Wounds are injuries to living tissue caused by a cut, blow, or other impact. There are numerous nanogels having different polymer compositions that have been reported to enhance the wound healing process, such as hyaluronan, poly-L-lysine, and berberine. When antimicrobial resistance is present, wound healing becomes a complicated process. Researchers are looking for novel alternative approaches, as foreign microorganisms in wounds are becoming resistant to antibiotics. Silver nanogels have been reported as a popular antimicrobial choice, as silver has been used as an antimicrobial throughout a prolonged period. Lignin-incorporated nanogels and lidocaine nanogels have also been reported as an antioxidant wound-dressing material that can aid in wound healing. In this review, we will summarize recent progress in biomedical applications for various nanogels, with a prime focus on cancer and wound healing. Full article

Background: Ulcerative colitis (UC), a subtype of chronic inflammatory bowel disease (IBD), is primarily treated with oral medications to reduce inflammation and alleviate symptoms. Celecoxib (CXB) is an attractive candidate for UC; however, its limited solubility and low bioavailability pose significant challenges to its clinical application. Methods: We reported a novel chondroitin sulfate A–Celecoxib (CSA-CXB) polymeric nanoprodrug to address the limited solubility and low bioavailability of CXB. CXB was conjugated to chondroitin sulfate A (CSA) via succinic anhydride (SA) and ethylenediamine to prepare CSA-CXB polymers, which can self-assemble into nanoparticle structural prodrugs in aqueous condition. We investigated the stability, blood compatibility, and responsiveness of the nanoparticles. The ability of the nanoparticles to treat UC in vitro and in vivo was then evaluated. Results: The CSA-CXB nanoprodrug was spherical with a mean particle size of 188.4 ± 2.2 nm, a zeta potential of −22.9 ± 0.1 mV, and sustained drug release behavior. Furthermore, CSA-CXB exhibited remarkable antioxidant and anti-inflammatory effects, as it can significantly increase the free radical scavenging rate and reduce the expression level of ROS, TNF-α, IL-6, nitric oxide (NO), and COX-2 protein in vitro. In vivo results demonstrated that CSA-CXB targeted the mice’s colon efficiently mitigate UC symptoms by inhibiting the expression of inflammatory cytokine. Conclusions: The CSA-CXB nanoprodrug can improve the therapeutic impact of CXB, and has potential as a new preparation for a clinical UC treatment nanoprodrug. Full article

Sesaminol is a natural functional compound of sesame with low bioaccessibility due to its high crystallinity. Here, a peptide-based self-assembly microgel was constructed to encapsulate sesaminol, reducing its crystallinity and improving its bioaccessibility. In this contribution, the peptide AcNH-Leu-Tyr-Tyr-CONH₂ (LYY) was shown to form a mesoporous three-dimensional (3D) microgel through microstructure characterization. Various characterization methods revealed that the LYY peptide self-assembled through β-folds and random coils, and the primary intermolecular interactions arose from hydrogen bonding and the π-π stacking effect. Subsequently, sesaminol was encapsulated within the microgel through co-assembly. The maximum encapsulation efficiency of sesaminol was 80.8 ± 0.9%, mainly in the form of nanoparticles encapsulated in microgel by morphology characterization. The XRD results indicated that sesaminol primarily existed in an amorphous state following encapsulation. The cumulative release indicated that sesaminol had a sustained release effect in the encapsulation system. Its bioaccessibility and antioxidant levels were increased. Molecular docking indicated that the main interactions between sesaminol and the self-assembled structure were hydrogen bonding and π-π interactions. Establishing sesaminol encapsulation provides valuable data and theoretical support for the research of sesaminol and the sesame processing industry. Full article

The purpose of this study was to design nanocarriers with small-size and antioxidant properties for the effective encapsulation of curcumin. Here, procyanidins, vanillin, and amino acids were used to successfully prepare nanocarriers of a controllable size in the range of 328~953 nm and to endow antioxidant ability based on a one-step self-assembly method. The reaction involved a Mannich reaction on the phenolic hydroxyl groups of procyanidins, aldehyde groups of vanillin, and amino groups of amino acids. Subsequently, curcumin nanoparticles were prepared by loading curcumin with this nanocarrier, and the encapsulation efficiency of curcumin was 85.97%. Compared with free curcumin, the antioxidant capacity and photothermal stability of the embedded curcumin were significantly improved, and it could be slowly released into simulated digestive fluid. Moreover, using the corticosterone-induced PC12 cell injury model, the cell viability increased by 23.77% after the intervention of curcumin nanoparticles, and the cellular antioxidant capacity was also significantly improved. The nanoparticles prepared in this work can effectively improve the solubility, stability, and bioactivity of curcumin, which provides a reference for the embedding and delivery of other hydrophobic bioactive compounds. Full article

Natural polyphenolic compounds play a pivotal role in biological processes and exhibit notable antioxidant activity. Among these compounds, chlorogenic acid stands out as one of the most widespread and important polyphenols. The accurate detection of chlorogenic acid is crucial for ensuring the quality and classification of the raw materials used in its extraction, as well as the final products in the food, pharmaceutical, and cosmetics industries that contain this bioactive compound. Raman spectroscopy emerges as a powerful analytical tool, particularly in field applications, due to its versatility and sensitivity, offering both qualitative and quantitative analyses. By using the self-assembly of gold nanoparticles at liquid–liquid interfaces and the developed “aqua-print” process, we propose a facile and inexpensive route to fabricate enhanced substrates for surface-enhanced Raman spectroscopy with high reproducibility. To ensure substrate reliability and accurate molecule detection in SERS experiments, a benchmarking procedure was developed. This process involved the use of non-resonant rhodamine 6G dye in the absence of charge transfer and was applied to all synthesized nanoparticles and fabricated substrates. The latter revealed the highest enhancement factor of 4 × 10⁴ for 72 nm gold nanoparticles among nanoparticle diameters ranging from 14 to 99 nm. Furthermore, the enhanced substrate was implemented in the detection of chlorogenic acid with a concentration range from 10 μM to 350 μM, demonstrating high accuracy (R² > 99%). Raman mapping was employed to validate the good uniformity of the signal (the standard deviation was below 15%). The findings of this study were also supported by DFT calculations of the theoretical Raman spectra, demonstrating the formation of the chlorogenic acid dimer. The proposed method is strategically important for the development of the class of in-field methods to detect polyphenolic compounds in raw materials such as plants, extracted plant proteins, and polyphenolic compounds. Full article

Carotenoids are increasingly used as naturally occurring food colorants. For application as beverage colorants, fat-soluble carotenoids are formulated into dispersion systems via nanoparticle (NP) formation. In recent years, the antioxidant properties of carotenoids have gained immense recognition for their preventive health benefits, thereby highlighting further interest in their development as functional food ingredients. Although functional carotenoids in dispersion-based formulations are desirable, knowledge regarding the structural and optical properties of NPs of carotenoids other than those of β-carotene, and methods to efficiently produce and compare NPs of various carotenoids, remain scarce. In this study, NPs of β-carotene, lycopene, astaxanthin, and lutein were prepared using a simple reprecipitation method, with a focus on understanding the variations in the molecular self-assembly influenced by the quality of solvent used during reprecipitation. This study presents the novel finding that the terminal groups of carotenoids significantly affect the intermolecular interactions, thereby altering the structural and optical properties of the resulting NPs. Our findings are expected to contribute to the development of new technologies for controlling the color of carotenoids based on the crystal structure of the NPs. Full article

(1) Objective: To optimize the preparation process of hyaluronic acid-modified ginsenoside Rb1 self-assembled nanoparticles (HA@GRb1@CS NPs), characterize and evaluate them in vitro, and investigate the mechanism of action of HA@GRb1@CS NPs in treating cardiovascular diseases (CVDs) associated with inflammation and oxidative stress. (2) Methods: The optimal preparation process was screened through Plackett–Burman and Box–Behnken designs. Physical characterization of HA@GRb1@CS NPs was conducted using transmission electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. Stability experiments, in vitro drug release studies, and lyophilisate selection were performed to evaluate the in vitro performance of HA@GRb1@CS NPs. The anti-inflammatory and antioxidant capabilities of HA@GRb1@CS NPs were assessed using H9c2 and RAW264.7 cells. Additionally, bioinformatics tools were employed to explore the mechanism of action of HA@GRb1@CS NPs in the treatment of CVDs associated with inflammation and oxidative stress. (3) Results: The optimal preparation process for HA@GRb1@CS NPs was achieved with a CS concentration of 2 mg/mL, a TPP concentration of 2.3 mg/mL, and a CS to TPP mass concentration ratio of 1.5:1, resulting in a particle size of 126.4 nm, a zeta potential of 36.8 mV, and a PDI of 0.243. Characterization studies confirmed successful encapsulation of the drug within the carrier, indicating successful preparation of HA@GRb1@CS NPs. In vitro evaluations demonstrated that HA@GRb1@CS NPs exhibited sustained-release effects, leading to reduced MDA (Malondialdehyde) content and increased SOD (Superoxide Dismutase) content in oxidatively damaged H9c2 cells. Furthermore, it showed enhanced DPPH (2,2-Diphenyl-1-picrylhydrazyl) and ABTS⁺ [2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)] free radical scavenging rates and inhibited the release of inflammatory factors NO (Nitric Oxide) and IL-6 (Interleukin-6) from RAW264.7 cells. (4) Conclusions: The HA@GRb1@CS NPs prepared in this study exhibit favorable properties with stable quality and significant anti-inflammatory and antioxidant capabilities. The mechanisms underlying their therapeutic effects on CVDs may involve targeting STAT3, JUN, EGFR, CASP3, and other pathways regulating cell apoptosis, autophagy, anti-lipid, and arterial sclerosis signaling pathways. Full article

Plant proteins have gained significant attention over animal proteins due to their low carbon footprint, balanced nutrition, and high sustainability. These attributes make plant protein nanocarriers promising for applications in drug delivery, nutraceuticals, functional foods, and other areas. Zein, a major by-product of corn starch processing, is inexpensive and widely available. Its unique self-assembly characteristics have led to its extensive use in various food and drug systems. Zein’s functional tunability allows for excellent performance in loading and transporting bioactive substances. Lutein offers numerous bioactive functions, such as antioxidant and vision protection, but suffers from poor chemical stability and low bioavailability. Nano-embedding technology can construct various zein-loaded lutein nanodelivery systems to address these issues. This review provides an overview of recent advances in the construction of zein-loaded lutein nanosystems. It discusses the fundamental properties of these systems; systematically introduces preparation techniques, structural characterization, and functional properties; and analyzes and predicts the target-controlled release and bioaccessibility of zein-loaded lutein nanosystems. The interactions and synergistic effects between Zein and lutein in the nanocomplexes are examined to elucidate the formation mechanism and conformational relationship of zein–lutein nanoparticles. The physical and chemical properties of Zein are closely related to the molecular structure. Zein and its modified products can encapsulate and protect lutein through various methods, creating more stable and efficient zein-loaded lutein nanosystems. Additionally, embedding lutein in Zein and its derivatives enhances lutein’s digestive stability, solubility, antioxidant properties, and overall bioavailability. Full article

In this study, a novel and simple strategy is proposed based on 3D network formed by easily blending polysaccharide carrageenan (Car) and fucoidan (Fuc) without a crosslinker. The Fuc/Car dual coating effectively assists the self-assembly of soy protein-isolated (SPI)/curcumin (Cur, C) composite microcapsules (SPI/C) and achieves an excellent curcumin encapsulation efficiency (EE) up to 95.28% with a 4.16% loading capacity (LC) under optimal conditions. The resulting nanocomposites achieved a satisfying redispersibility in aqueous solution and enhanced the water solubility with a lower size dispersity index (PDI) of 0.12 and a larger zeta potential of −29.67 mV. The Fuc/Car double-layer network not only dramatically improved its thermal stability and photostability, but also provided controlled release and enhanced antioxidant activity in in vitro conditions. The underlying mechanism of the self-assembly of the curcumin-loaded nanoparticles was also addressed. The results proved the feasibility of the encapsulation of unstable hydrophobic bioactive substances (curcumin) with the dual anionic polysaccharide Fuc/Car co-stabilized SPI nanoparticles. This study paves the way for an alternative way of developing novel curcumin delivery systems and will have broad prospects in the pharmaceutical industries. Full article

Lignin, a main byproduct from paper manufacturing and biorefineries, is now emerging as a new low-cost, renewable starting material for new product development. Its biocompatibility and safety make it valuable for creating novel and value-added products. Lignin, a polymer with many hydrophilic and active groups, confers many useful properties. However, there are several challenges to overcome due to its complex chemical structure and heterogeneous self-assembly behavior. Nanostructured systems using lignin could address these challenges, finding applications in food science, cosmetics, and healthcare. This study explores two main green synthesis approaches for lignin nanoparticles: bottom-up based on the self-assembly in a solvent–antisolvent system and top-down based on the ultrasonication. These nanoparticles are evaluated for morphology, estimation of phenolic content and antioxidant effects. Specifically, the antisolvent nanostructures show a spherical conformation with a higher antioxidant activity due to a better organization of phenolic hydroxyl groups. Obtained result have been exploited to draw an efficient and cheap technological route for lignin valorization. Full article