Highly efficient and broad-spectrum antibacterial carbon dots combat antibiotic resistance.

Bacterial infections have become a major global public health issue, particularly with the emergence of multidrug-resistant strains. Therefore, developing non-antibiotic antimicrobial agents is crucial for treating drug-resistant bacterial infections. Building on previous research into natural products as novel antibacterial agents, this study synthesized curcumin-derived carbon dots using curcumin and ethylenediamine as raw materials through a hydrothermal method. The resulting carbon dots not only improved the water solubility and stability of curcumin but also exhibited highly efficient broad-spectrum antibacterial activity. Detailed investigations into the antibacterial performance and mechanisms of the carbon dots were conducted through experiments such as minimum inhibitory concentration (MIC) determination, live/dead bacterial staining, morphological studies, nucleic acid concentration detection, and reactive oxygen species (ROS) detection. The results indicated that the carbon dots significantly damaged the structural integrity of bacteria and generated large amounts of ROS. They exhibited remarkable antibacterial effects against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, and effectively inhibited drug-resistant MRSA. Their antibacterial efficacy was notably superior to that of broad-spectrum antibiotics such as chloramphenicol and Sulfadiazine. This study highlights the potential application of curcumin-derived carbon dots in combating bacterial infections and provides valuable insights for developing novel antibacterial agents derived from natural products.

Biocompatible sensors for ammonia gas detection.

In this work, three different dyes have been tested for the determination of gaseous ammonia. This gas is one of the products of microbial degradation and therefore its presence is an indicator of deterioration and could be used as a food freshness indicator. Three different sensors have been prepared and tested, two of them using the natural pigments curcumin and anthocyanin and the other one using bromothymol blue. All of them are biocompatible and therefore allowed to use in contact with food. Different compositions, materials for deposition, stability and reversibility for ammonia gas detection have been studied under high humidity conditions simulating real packaged food conditions. Colorimetry is the technique used to obtain the analytical parameter, the H coordinate of the HSV colour space, simply using a camera, avoiding the use of complex instrumentation. Sensibility, toxicity grade and stability found show that the sensor could be implemented in packaged food and form the basis of a freshness indicator for the food industry.

A computer-aided, heterodimer-based "triadic" carrier-free drug delivery platform to mitigate multidrug resistance in lung cancer and enhance efficiency.

Co-delivering multiple drugs or circumventing the drug efflux mechanism can significantly decrease multidrug resistance (MDR), a major cause of cancer treatment failure. In this study, we designed and fabricated a universal "three-in-one" self-delivery system for synergistic cancer therapy using a computer-aided strategy. First, we engineered two glutathione (GSH)-responsive heterodimers, ERL-SS-CPT (erlotinib [ERL] linked with camptothecin [CPT] via a disulfide bond [SS]) and CPT-SS-ERI (CPT conjugated with erianin [ERI]), which serve as both cargo and carrier material. Next, molecular dynamics simulations indicated that multiple noncovalent molecular forces, including π-π stacking, hydrogen bonds, hydrophobic interactions, and sulfur bonds, drive the self-assembly process of these heterodimers. We then explored the universality of the heterodimers and developed a "triadic" drug delivery platform comprising 40 variants. Subsequently, we conducted case studies on docetaxel (DTX)-loaded ERL-SS-CPT nanoparticles (denoted as DTX@ERL-SS-CPT NPs) and curcumin (CUR)-loaded ERL-SS-CPT NPs (identified as CUR@CPT-SS-ERI NPs) to comprehensively investigate their self-assembly mechanism, physicochemical properties, storage stability, GSH-responsive drug release, cellular uptake, apoptosis effects, biocompatibility, and cytotoxicity. Both NPs exhibited well-defined spherical structures, high drug loading rates, and excellent storage stability. DTX@ERL-SS-CPT NPs exhibited the strongest cytotoxicity in A549 cells, following the order of DTX@ERL-SS-CPT NPs > ERL-SS-CPT NPs > CPT > DTX > ERL. Conversely, DTX@ERL-SS-CPT NPs showed negligible cytotoxicity in normal human bronchial epithelium cell line (BEAS-2B), indicating good biocompatibility and safety. Similar observations were made for CUR@CPT-SS-ERI NPs regarding biocompatibility and cytotoxicity. Upon endocytosis and encountering intracellular overexpressed GSH, the disulfide-bond linker is cleaved, resulting in the release of the versatile NPs into three parts. The spherical NPs enhance water solubility, reduce the required dosage of free drugs, and increase cellular drug accumulation while suppressing P-glycoprotein (P-gp) expression, leading to apoptosis. This work provides a computer-aided universal strategy-a heterodimer-based "triadic" drug delivery platform-to enhance anticancer efficiency while reducing multidrug resistance.

SARS-CoV-2 surrogate bacteriophage φ6 cross-contamination between fruits and gloves, survival on discarded gloves and inactivation by photodynamic treatment.

This study assessed the SARS-CoV-2 surrogate bacteriophage φ6 cross-contamination between high-density polyethylene or polyvinyl chloride gloves and fruits (tomato and cucumber) using different inoculum levels (6.0 and 4.0 log PFU/sample). Bacteriophage φ6 survival on contaminated gloves was assessed over 9 days at 25 °C. The effectiveness of photodynamic treatment using curcumin as a photosensitizer to inactivate φ6 on fruits was determined. The fruit type and the glove material influenced the φ6 transfer. Longer contact times resulted in greater φ6 transfer. The highest φ6 transfer occurred from tomato to HDPE glove (0.8% or -1.1 log % transfer) after 30 s of contact at the higher inoculum level. Bacteriophage φ6 was detected on cross-contaminated HDPE gloves for up to 6 days. Bacteriophage φ6 survived better on vinyl gloves cross-contaminated by cucumber vs. tomato (detected up to 6 vs 3 days). Photodynamic inactivation of φ6 was time-dependent and varied with the tested fruit but was not influenced by viral starting concentration. Photodynamic treatment decreased the φ6 titer by 3.0 and 2.2 log PFU/sample in tomato and cucumber, respectively. Transmission electronic microscopy showed that photodynamic treatment changed the structure of the φ6 capsid. These findings may help in the management of SARS-CoV-2 contamination risks in fruit handling. They may also help in the establishment of effective measures to manage cross-contamination risk.

Effect of cationized guar gum on stability and bioaccessibility of curcumin-loaded Pickering emulsion stabilized by starch nanoparticles.

To enhance stability and bioaccessibility of curcumin in Pickering emulsions stabilized by starch nanoparticles (SNP), cationized guar gum (CGG) was incorporated into the emulsion. Zeta potential results revealed that SNP and CGG formed electrostatic interactions, resulting in stable interfacial layer with higher hydrophobicity. Adding 0.4 % CGG maintained a homogeneous phase without significant droplet size change for up to one month. The emulsion with 0.4 % CGG demonstrated stable storage under varying pH (4-10), ionic strength (0-10 mM NaCl), and freeze-thaw cycles (up to 3). When optimized Pickering emulsion system was applied to curcumin encapsulation, curcumin-loaded emulsions were stably maintained for up to one month. The curcumin retained approximately 100 % stability under thermal (90 °C) and UV (12h) treatments. In the optimized emulsion, starch components resisted digestion in oral and gastroenteric phases but were primarily digested in small intestine, resulting in an increasing bioaccessibility from 88.23 to 96.92 %.

Fish freshness monitoring based on bilayer cellulose acetate/polyvinylidene fluoride membranes containing ZIF-8 loaded curcumin.

This study presented a dual-layer freshness indicator film produced through electrospinning, combining cellulose acetate and polyvinylidene fluoride with zeolitic imidazolate framework-8 (ZIF-8) loaded with curcumin as the indicator. Our findings demonstrated that ZIF-8 effectively preserved its metal-organic framework structure during curcumin loading, ensuring the inherent color-changing ability of curcumin. The resulting colorimetric film exhibited altered tensile properties and increased water vapor permeability. Improved light stability and storage performance were observed. Compared to single-layer films, the dual-layer structure improved the hydrophilicity and stability of the indicator film. Importantly, the introduced indicator label efficiently captured the dynamic changes of TVB-N during freshness monitoring, providing comprehensive visual information for assessing fish freshness. The synergistic properties of ZIF-8, curcumin, and the dual-layer film structure contributed to an advanced freshness indicator system, providing a multifunctional and effective approach for real-time freshness assessment of fish freshness.

Modifying the interfacial dynamics of oleosome (lipid droplet) membrane using curcumin.

Cells store energy in lipid droplets, known as oleosomes, which have a neutral lipid core surrounded by a dilatable membrane of phospholipids and proteins. Oleosomes can be loaded with therapeutic lipophilic cargos through their permeable membrane and used as carriers. However, the cargo can also adsorb between the phospholipids and affect the membrane properties. In the present work, we investigated the effect of adsorbed curcumin on the mechanical properties of oleosome membranes using dilatational interfacial rheology (LAOD). The oleosome membrane had a weak-stretchable behavior, while the adsorption of curcumin led to stronger in-plane interactions, which were dependent on curcumin concentration and indicated a glassy-like structure. Our findings showed that adsorbed curcumin molecules can enhance the molecular interactions on the oleosome membrane. This behavior suggests that oleosomes membranes can be modulated by loaded cargo. Understanding cargo and membrane interactions can help to design oleosome-based formulations with tailored mechanical properties for applications.

Biocompatible Poly(ε-Caprolactone) Nanocapsules Enhance the Bioavailability, Antibacterial, and Immunomodulatory Activities of Curcumin.

Curcumin (Cur), the primary curcuminoid found in Curcuma longa L., has garnered significant attention for its potential anti-inflammatory and antibacterial properties. However, its hydrophobic nature significantly limits its bioavailability. Additionally, adipose-derived stem cells (ADSCs) possess immunomodulatory properties, making them useful for treating inflammatory and autoimmune conditions. This study aims to verify the efficacy of poly(ε-caprolactone) nanocapsules (NCs) in improving Cur's bioavailability, antibacterial, and immunomodulatory activities. The Cur-loaded nanocapsules (Cur-NCs) were characterized for their physicochemical properties (particle size, polydispersity index, Zeta potential, and encapsulation efficiency) and stability over time. A digestion test simulated the behavior of Cur-NCs in the gastrointestinal tract. Micellar phase analyses evaluated the Cur-NCs' bioaccessibility. The antibacterial activity of free Cur, NCs, and Cur-NCs against various Gram-positive and Gram-negative strains was determined using the microdilution method. ADSC viability, treated with Cur-NCs and Cur-NCs in the presence or absence of lipopolysaccharide, was analyzed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay. Additionally, ADSC survival was assessed through the Muse apoptotic assay. The expression of both pro-inflammatory (interleukin-1ß and tumor necrosis factor-α) and anti-inflammatory (IL-10 and transforming growth factor-ß) cytokines on ADSCs was evaluated by real-time polymerase chain reaction. The results demonstrated high stability post-gastric digestion of Cur-NCs and elevated bioaccessibility of Cur post-intestinal digestion. Moreover, Cur-NCs exhibited antibacterial activity against Escherichia coli without affecting Lactobacillus growth. No significant changes in the viability and survival of ADSCs were observed under the experimental conditions. Finally, Cur-NCs modulated the expression of both pro- and anti-inflammatory cytokines in ADSCs exposed to inflammatory stimuli. Collectively, these findings highlight the potential of Cur-NCs to enhance Cur's bioavailability and therapeutic efficacy, particularly in cell-based treatments for inflammatory diseases and intestinal dysbiosis.

Drug Combination Studies of Isoquinolinone AM12 with Curcumin or Quercetin: A New Combination Strategy to Synergistically Inhibit 20S Proteasome.

In the eukaryotic cells, the ubiquitin-proteasome system (UPS) plays a crucial role in the intracellular protein turnover. It is involved in several cellular functions such as the control of the regular cell cycle progression, the immune surveillance, and the homeostasis. Within the 20S proteasome barrel-like structure, the catalytic subunits, ß1, ß2 and ß5, are responsible for different proteolytic activities: caspase-like (C-L), trypsin-like (T-L) and chymotrypsin-like (ChT-L), respectively. The ß5 subunit is particularly targeted for its role in antitumor activity: the synthesis of ß5 subunit inhibitors could be a promising strategy for the treatment of solid and hematologic tumors. In the present work, we performed two combination studies of AM12, a recently developed synthetic proteasome inhibitor, with curcumin and quercetin, two nutraceuticals endowed of many pharmacological properties. We measured the combination index (CI), applying the Chou and Talalay method, comparing the two studies, from 50% to 90% of proteasome inhibition. In the case of the combination AM12 + curcumin, an increasing synergism was observed from 50% to 90% of proteasome inhibition, while in the case of the combination AM12 + quercetin an additive effect was observed only from 50% to 70% of ß5 subunit inhibition. These results suggest that combining AM12 with curcumin is a more promising strategy than combining it with quercetin for potential therapeutic applications, especially in treating tumors.

Quaternized Curcumin Derivative-Synthesis, Physicochemical Characteristics, and Photocytotoxicity, Including Antibacterial Activity after Irradiation with Blue Light.

Over the past few years, numerous bacterial strains have become resistant to selected drugs from various therapeutic groups. A potential tool in the fight against these strains is antimicrobial photodynamic therapy (APDT). APDT acts in a non-specific manner by generating reactive oxygen species and radicals, thereby inducing multidimensional intracellular effects. Importantly, the chance that bacteria will develop defense mechanisms against APDT is considered to be low. In our research, we performed the synthesis and physicochemical characterization of curcumin derivatives enriched with morpholine motifs. The obtained compounds were assessed regarding photostability, singlet oxygen generation, aggregation, and acute toxicity toward prokaryotic Aliivibrio fischeri cells in the Microtox® test. The impact of the compounds on the survival of eukaryotic cells in the MTT assay was also tested (WM266-4, WM115-melanoma, MRC-5-lung fibroblasts, and PHDF-primary human dermal fibroblasts). Initial studies determining the photocytotoxicity, and thus the potential APDT usability, were conducted with the following microbial strains: Candida albicans, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa. It was noted that the exposure of bacteria to LED light at 470 nm (fluence: 30 J/cm2) in the presence of quaternized curcumin derivatives at the conc. of 10 µM led to a reduction in Staphylococcus aureus survival of over 5.4 log.

Curcumin-Based Molecularly Imprinted Polymer Electropolymerized on Single-Use Graphite Electrode for Dipyridamole Analysis.

A new molecularly imprinted polymer (MIP)-based disposable electrochemical sensor for dipyridamole (DIP) determination was obtained. The sensor was rapidly prepared by potentiodynamic electrochemical polymerization on a pencil graphite electrode (PGE) using curcumin (CUR) as a functional monomer and DIP as a template molecule. After the optimization of the conditions (pH, monomer-template ratio, scan rate, number of cyclic voltammetric cycles applied in the electro-polymerization process and extraction time of the template molecule) for MIP formation, DIP voltammetric behavior at the modified electrode (MIP_PGE) was investigated. DIP oxidation took place in a pH-dependent, irreversible mixed diffusion-adsorption controlled process. Differential pulse voltammetry (DPV) and adsorptive stripping differential pulse voltammetry (AdSDPV) were used to quantify DIP from pharmaceutical and tap water samples. Under optimized conditions (Britton-Robinson buffer at pH = 3.29), the obtained linear ranges were 5.00 × 10-8-1.00 × 10-5 mol/L and 5.00 × 10-9-1.00 × 10-7 mol/L DIP for DPV and AdSDPV, respectively. The limits of detection of the methods were 1.47 × 10-8 mol/L for DPV and 3.96 × 10-9 mol/L DIP for AdSDPV.

Curcumin-Loaded Nanocomposite Hydrogel Dressings for Promoting Infected Wound Healing and Tissue Regeneration.

Background: The skin regulates body processes. When damaged, it is prone to breeding bacteria, causing inflammation and impeding wound healing. There is an urgent need for new dressings that can combat bacteria to aid in infectious wound repair. Methods: In this study, a curcumin-loaded nanocomposite hydrogel dressing (GelMA/AHA-Gel@Cur) with antibacterial properties and strong toughness was synthesized, designed to combine the modified gelatin-based hydrogel (GelMA/AHA) with curcumin-coated gelatin (Gel@Cur) nanoparticles to promote the healing of bacterial infection wounds. Under UV irradiation, methylacrylylated gelatin (GelMA) and aldehyaluronic acid (AHA) formed a composite network hydrogel through radical polymerization and Schiff base reaction. Meanwhile, the residual aldehyde group on the molecular chain of AHA securely locked Gel@Cur nanoparticles in the hydrogel network through Schiff base reaction. Results: The addition of Gel@Cur nanoparticles not only enhanced the hydrogel's mechanical strength but also facilitated a sustained, gradual release of curcumin, endowing the composite hydrogel with robust antimicrobial capabilities. In an animal model of infected wounds, the composite hydrogel significantly improved wound closure, healing, and vascularization compared to the control group. Hemocompatibility tests confirmed the hydrogel's safety, with a hemolysis ratio of just 0.45%. Histological evaluation following treatment with the composite hydrogel showed improved tissue architecture, increased collagen deposition, and regeneration of dermal gland structures. Conclusion: The GelMA/AHA-Gel@Cur composite hydrogel exhibits excellent mechanical properties, potent antimicrobial activity, and controlled drug release, along with superior cell and hemocompatibility. These characteristics make it a promising material for infected wound repair and a potential candidate for clinical skin regeneration applications.

Magnesium metal-organic framework microneedles loaded with curcumin for accelerating oral ulcer healing.

Oral ulcers are a common oral mucosal disease that seriously affect the quality of life. Traditional drug treatments have shown unsatisfactory efficacy and potential adverse reactions. In this study, curcumin-loaded multifunctional magnesium metal-organic framework-embedded hyaluronic acid-soluble microneedles patches were developed to optimize treatment strategies for oral ulcers. This microneedles patch achieves efficient release of curcumin and Mg2+ in the ulcer through precisely targeted delivery and controllable release mechanism, significantly regulates inflammation, promotes cell migration and angiogenesis, and accelerates the ulcer healing process. At the same time, the synergistic effect of curcumin and gallic acid effectively alleviated oxidative stress, while the backplate ε-poly-L-lysine and needle tip Mg2+ jointly constructed an antibacterial barrier to effectively inhibit pathogens. Verification using an oral ulcer rat model showed that the microneedles patch exhibited excellent therapeutic effects. This not only opens up a new avenue for clinical oral treatment but also marks a breakthrough in nanobiomaterials science and drug delivery technology and heralds a broad prospect in the field of oral ulcer treatment in the future.

Inhibition of HIV-1 infection with curcumin conjugated PEG-citrate dendrimer; a new nano formulation.

BACKGROUND: Nano-drug delivery systems have become a promising approach to overcoming problems such as low solubility and cellular uptake of drugs. Along with various delivery devices, dendrimers are widely used through their unique features. PEG-citrate dendrimers are biocompatible and nontoxic, with the ability to improve drug solubility. Curcumin, a naturally occurring polyphenol, has multiple beneficial properties, such as antiviral activities. However, its optimum potential has been significantly hampered due to its poor water solubility, which leads to reduced bioavailability. So, the present study attempted to address this issue and investigate its antiviral effects against HIV-1. METHOD: The G2 PEG-citrate dendrimer was synthesized. Then, curcumin was conjugated to it directly. FTIR, HNMR, DLS, and LCMS characterized the structure of products. The conjugate displayed an intense yellow color. In addition, increased aqueous solubility and cell permeability of curcumin were achieved based on flow cytometry results. So, it could be a suitable vehicle for improving the therapeutic applications of curcumin. Moreover, cell toxicity was assessed using XTT method. Ultimately, the SCR HIV system provided an opportunity to evaluate the level of HIV-1 inhibition by the curcumin-dendrimer conjugate using a p24 HIV ELISA kit. RESULTS: The results demonstrated a 50% up to 90% inhibition of HIV proliferation at 12 µm and 60 µm, respectively. Inhibition of HIV-1 at concentrations much lower than CC50 (300 µM) indicates a high potential of curcumin-dendrimer conjugate against this virus. CONCLUSION: Thereby, curcumin-dendrimer conjugate proves to be a promising tool to use in HIV-1 therapy.

Novel ophthalmic hyaluronic acid-hydrogel with curcumin nanoparticles for enhanced healing of ulcerative keratitis in rabbit model.

Corneal ulcers, whether melting or indolent, are common in humans and companion animals. Treatment involves local administration of antibiotic eye drops and corneal healing drugs. Compared to traditional treatments for ulcerative keratitis, herbal medicines offer unique advantages, such as potent anti-inflammatory effects and inhibition of proinflammatory cytokines. Curcumin, extracted from the Curcuma Longa plant, possesses extensive pharmacological properties, such as anti-inflammatory, anti-cancer, and antioxidant properties, and is used in various medicines. In this study, we developed a novel ophthalmic drop hydrogel using a formulation of Curcumin NPs encapsulated with ß-cyclodextrin and hyaluronic acid, to accelerate corneal healing and improve the quality of healed structures. The formation of Curcumin NPs into Hyaluronic acid-based hydrogels was characterized by zeta, FTIR, and scanning electron microscope (SEM) analyses. A total of 25 healthy male New Zealand Albino rabbits were experimentally induced with ulcerative keratitis and treated individually with topical medication. Rabbits were divided into five groups. Fluorescein dye staining, corneal clarity score, Schirmer tear test, proinflammatory cytokine measurement, and pathologic factors assessments were used to evaluate the optimised Curcumin NPs with ß-cyclodextrin in Hyaluronic acid hydrogel. Our results demonstrated that the optimized Curcumin NPs with ß-cyclodextrin in hyaluronic acid hydrogel significantly reduced the frequency of medication administration compared to conventional therapies, enhancing the quality of healed structures and effectively treating ulcerative keratitis. All findings in this study provide new insight into designing and fabricating novel ophthalmic medicine for ulcerative keratitis for topical usage.

Effects of photodynamic therapy using bisdemethoxycurcumin combined with melatonin or acetyl-melatonin on C. Albicans.

The current study aims to explore the efficacy of antifungal photodynamic therapy (PDT) on C. albicans biofilms by combining photosensitizers, bisdemethoxycurcumin (BDMC), and melatonin (MLT) or acetyl-melatonin (AcO-MLT). Additionally, the relationship between different types of reactive oxygen species and PDT's antifungal efficacy was investigated. BDMC, MLT and AcO-MLT were applied, alone and in combination, to 48-hour C. albicans biofilm cultures (n = 6/group). Blue and red LED light (250 mW/cm2 with 37.5 J/cm2 for single or 75 J/cm2 for dual photosensitizer groups) were used to irradiate BDMC groups and MLT/AcO-MLT groups, respectively. For combination groups, blue LEDs and subsequently red LEDs were used. Drop plate assays were performed at 0, 1 and 6 h post-treatment. Colony forming units (CFUs) were then counted after 48 h. Hydroxyl radicals and singlet oxygen were measured using fluorescence spectroscopy and electron spin resonance (ESR) spectroscopy. Additionally, cell cytotoxicity was tested on human oral keratinocytes. Significant CFU reductions were observed with combinations 20 µM BDMC + 20 µM AcO-MLT and 60 µM BDMC + 20 µM MLT at 0 and 1 h post-treatment, respectively. Singlet oxygen production increased with the addition of MLT/AcO-MLT and had moderate-substantial correlations with inhibition at all times. Hydroxyl radical production was not significantly different from the control. Additionally, BDMC exhibited subtle cytotoxicity on human oral keratinocytes. PDT using BDMC + MLT or AcO-MLT, with blue and red LED light, effectively inhibits C. albicans biofilm through singlet oxygen generation. Melatonin acts as a photosensitizer in PDT to inhibit fungal infection.

Modified Ce/Zr-MOF Nanoparticles Loaded with Curcumin for Alzheimer's Disease via Multifunctional Modulation.

Introduction: Alzheimer's disease (AD), a neurodegenerative condition, stands as the most prevalent form of dementia. Its complex pathological mechanisms and the formidable blood-brain barrier (BBB) pose significant challenges to current treatment approaches. Oxidative stress is recognized as a central factor in AD, underscoring the importance of antioxidative strategies in its treatment. In this study, we developed a novel brain-targeted nanoparticle, Ce/Zr-MOF@Cur-Lf, for AD therapy. Methods: Layer-by-layer self-assembly technology was used to prepare Ce/Zr-MOF@Cur-Lf. In addition, the effect on the intracellular reactive oxygen species level, the uptake effect by PC12 and bEnd.3 cells and the in vitro BBB permeation effect were investigated. Finally, the mouse AD model was established by intrahippocampal injection of Aß1-42, and the in vivo biodistribution, AD therapeutic effect and biosafety of the nanoparticles were researched at the animal level. Results: As anticipated, Ce/Zr-MOF@Cur-Lf demonstrated efficient BBB penetration and uptake by PC12 cells, leading to attenuation of H2O2-induced oxidative damage. Moreover, intravenous administration of Ce/Zr-MOF@Cur-Lf resulted in rapid brain access and improvement of various pathological features of AD, including neuronal damage, amyloid-ß deposition, dysregulated central cholinergic system, oxidative stress, and neuroinflammation. Conclusion: Overall, Ce/Zr-MOF@Cur-Lf represents a promising approach for precise brain targeting and multi-target mechanisms in AD therapy, potentially serving as a viable option for future clinical treatment.

Curcumin/pEGCG-encapsulated nanoparticles enhance spinal cord injury recovery by regulating CD74 to alleviate oxidative stress and inflammation.

Spinal cord injury (SCI) often accompanies impairment of motor function, yet there is currently no highly effective treatment method specifically for this condition. Oxidative stress and inflammation are pivotal factors contributing to severe neurological deficits after SCI. In this study, a type of curcumin (Cur) nanoparticle (HA-CurNPs) was developed to address this challenge by alleviating oxidative stress and inflammation. Through non-covalent interactions, curcumin (Cur) and poly (-)-epigallocatechin-3-gallate (pEGCG) are co-encapsulated within hyaluronic acid (HA), resulting in nanoparticles termed HA-CurNPs. These nanoparticles gradually release curcumin and pEGCG at the SCI site. The released pEGCG and curcumin not only scavenge reactive oxygen species (ROS) and prevents apoptosis, thereby improving the neuronal microenvironment, but also regulate CD74 to promote microglial polarization toward an M2 phenotype, and inhibits M1 polarization, thereby suppressing the inflammatory response and fostering neuronal regeneration. Moreover, in vivo experiments on SCI mice demonstrate that HA-CurNPs effectively protect neuronal cells and myelin, reduce glial scar formation, thereby facilitating the repair of damaged spinal cord tissues, restoring electrical signaling at the injury site, and improving motor functions. Overall, this study demonstrates that HA-CurNPs significantly reduce oxidative stress and inflammation following SCI, markedly improving motor function in SCI mice. This provides a promising therapeutic approach for the treatment of SCI.

Genetically engineered cellular nanoparticles loaded with curcuminoids for cancer immunotherapy.

Background: Inducing immunogenic cell death (ICD) is a promising strategy to enhance immune responses for immune checkpoint blockade (ICB) therapy, but the lack of a simple and effective platform to integrate ICD and ICB therapy limits their clinical application. Methods: Here, we developed programmed cell death protein 1 (PD1)-overexpressing genetically engineered nanovesicles (NVs)-coated curcumin (Cur)-loaded poly (lactic-co-poly-polyglycolic acid) nanoparticles (PD1@Cur-PLGA) to integrate ICD and ICB therapy for enhancing tumor immunotherapy. Results: Genetically engineered NVs greatly enhanced the tumor targeting of nanoparticles, and the PD1 on NVs dramatically blocked the PD1/PDL1 signaling pathway and stimulated antitumor immune responses. Meanwhile, the delivered Cur successfully induced tumor cell apoptosis and activated ICD by inhibiting NF-κB phosphorylation and Bcl-2 protein expression and activating caspase and Bax apoptotic signaling. By synergizing the ICD effect of Cur and the PD1/PDL1 axis blocking function of genetically engineered NVs, the PD1@Cur-PLGA enhanced the intratumoral infiltration rate of mature dendritic cells and CD8+ T cells in tumor tissues, resulting in significantly inhibiting tumor growth in breast and prostate tumor-bearing mouse models. Conclusion: This synergistic ICD and ICB therapy based on genetically engineered NVs provides a low-cost, safe, and effective strategy to enhance cancer immunotherapy.

Yeast encapsulation of photosensitive insecticides increases toxicity against mosquito larvae while protecting microorganisms.

An important defense against the deadly diseases that mosquitoes transmit is the application of insecticides that reduce mosquito populations. Unfortunately, the evolution and subsequent spread of insecticide resistance has decreased their efficacy. Therefore, new mosquito control strategies are needed. One class of larvicides, known as photosensitive insecticides, or PSIs, kills larvae via light-activated oxidative damage. PSIs are promising larvicides because of their high larvicidal efficacy, rapid photodegradation, inexpensive cost, and mechanism that is dissimilar to other insecticide classes. We explored a novel delivery strategy for increasing both the larvicidal efficiency and environmental biocompatibility of PSIs, known as yeast encapsulation. Using the PSIs, curcumin and methylene blue, we measured the survival of Anopheles gambiae larvae and Escherichia coli following exposure to either non-encapsulated or yeast-encapsulated PSIs and a photoperiod. Yeast encapsulation increased the phototoxicity of both curcumin and methylene blue against mosquito larvae, likely by increasing ingestion. Furthermore, yeast encapsulation protected E. coli from the phototoxicity of yeast-encapsulated curcumin, but not yeast-encapsulated methylene blue. Yeast encapsulation increases the larvicidal efficacy of a PSI while also increasing biocompatibility. Therefore, yeast encapsulation of PSIs is a promising insecticide delivery strategy for mosquito control.