RESUMEN

BACKGROUND: In allogeneic-hematopoietic stem cell transplantation for acute myeloid leukemia (AML), donor T cells combat leukemia through the graft-versus-leukemia (GVL) effect, while they also pose a risk of triggering life-threatening graft-versus-host disease (GVHD) by interacting with recipient cells. The onset of GVHD hinges on the interplay between donor T cells and recipient antigen-presenting cells (APCs), sparking T-cell activation. However, effective methods to balance GVHD and GVL are lacking. METHODS: In our study, we crafted nanocapsules by layering polycationic aminated gelatin and polyanionic alginate onto the surface of T cells, examining potential alterations in their fundamental physiological functions. Subsequently, we established an AML mouse model and treated it with transplantation of bone marrow cells (BMCs) combined with encapsulated T cells to investigate the GVL and anti-GVHD effects of encapsulated T cells. In vitro co-culture was employed to probe the effects of encapsulation on immune synapses, co-stimulatory molecules, and tumor-killing pathways. RESULTS: Transplantation of BMCs combined with donor T cells selectively encapsulated onto AML mice significantly alleviates GVHD symptoms while preserving essential GVL effects. Encapsulated T cells exerted their immunomodulatory effects by impeding the formation of immune synapses with recipient APCs, thereby downregulating co-stimulatory signals such as CD28-CD80, ICOS-ICOSL, and CD40L-CD40. Recipient mice receiving encapsulated T-cell transplantation exhibited a marked increase in donor Ly-5.1-BMC cell numbers, accompanied by unaltered in vivo expression levels of perforin and granzyme B. While transient inhibition of donor T-cell cytotoxicity in the tumor microenvironment was observed in vitro following single-cell nanoencapsulation, subsequent restoration to normal antitumor activity ensued, attributed to selective permeability of encapsulated vesicle shells and material degradation. Moreover, the expression of apoptotic proteins and FAS-FAS ligand pathway at normal levels was still observed in leukemia tumor cells. CONCLUSIONS: Encapsulated donor T cells effectively mitigate GVHD while preserving the GVL effect by minimizing co-stimulatory signaling with APCs through early immune isolation. Subsequent degradation of nanocapsules restores T-cell cytotoxic efficacy against AML cells, mediated by cytotoxic pathways. Using transplant-encapsulated T cells offers a promising strategy to suppress GVHD while preserving the GVL effect.

Asunto(s)

Modelos Animales de Enfermedad , Enfermedad Injerto contra Huésped , Leucemia Mieloide Aguda , Linfocitos T , Animales , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/inmunología , Ratones , Enfermedad Injerto contra Huésped/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Humanos , Efecto Injerto vs Leucemia , Nanocápsulas/química

RESUMEN

This study describes the comparison between the interaction of a series of peptide-functionalized chitosan-based nanocapsules and liposomes with two cell lines, i.e., mouse macrophages RAW 264.7 and human endothelial cells EA.hy926. Both types of nanocarriers are loaded with magnetic nanoparticles and designed for anti-inflammatory therapy. The choice of these magnetic nanostructures is argued based on their advantages in terms of size, morphology, chemical composition, and the multiple possibilities of modifying their surface. Moreover, active targeting might be ensured by using an external magnetic field. To explore the impact of chitosan-based nanocapsules and liposomes on cell cytophysiology, the cell viability, using the MTT assay, and cell morphology were investigated. The results revealed low to moderate cytotoxicity of free nanocapsules and significant cytotoxicity induced by chitosan-coated liposomes loaded with dexamethasone, confirming its release from the delivery system. Thus, after 48 h of treatment with nanocapsules, the viability of RAW 264.7 cells varied between 88.18% (OCNPM-1I, 3.125 µg/mL) and 76.37% (OCNPM-1, 25 µg/mL). In the same conditions, EA.hy926 cell viability was between 99.91% (OCNPM-3, 3.125 µg/mL) and 75.15% (OCNPM-3, 25 µg/mL) at the highest dose (25 µg/mL), the values being comparable for both cell lines. Referring to the cell reactivity after dexamethasone-loaded liposome application, the lowest viability of RAW 264.7 cells was 41.25% (CLDM5CP-1, 25 µg/mL) and 58.20% (CLDMM2CP-1 1.25 µg/mL) in the endothelial cell line, proving a selective character of action of nanocarriers. The cell morphology test, performed to support and confirm the results obtained by the MTT test, revealed a differentiated response for the two types of nano-carriers. As expected, an intense cytotoxic effect in the case of dexamethasone-loaded liposomes and a lack of cytotoxicity for drug-free nanocapsules were noticed. Therefore, our study demonstrated the biocompatible feature of the studied nanocarriers, which highlights them for future research as potential drug delivery systems for pharmacological applications, including anti-inflammatory therapy.

Asunto(s)

Antiinflamatorios , Supervivencia Celular , Quitosano , Liposomas , Nanocápsulas , Liposomas/química , Quitosano/química , Ratones , Nanocápsulas/química , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/administración & dosificación , Humanos , Células RAW 264.7 , Supervivencia Celular/efectos de los fármacos , Dexametasona/farmacología , Dexametasona/química , Dexametasona/administración & dosificación , Línea Celular , Nanopartículas de Magnetita/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología

RESUMEN

Insufficient angiogenic stimulation and dysregulated glycolipid metabolism in senescent vascular endothelial cells (VECs) constitute crucial features of vascular aging. Concomitantly, the generation of excess senescence-associated secretory phenotype (SASP) and active immune-inflammatory responses propagates within injured vessels, tissues, and organs. Until now, targeted therapies that efficiently rectify phenotypic abnormalities in senescent VECs have still been lacking. Here, we constructed a Pd/hCeO2-BMS309403@platelet membrane (PCBP) nanoheterostructured capsule system loaded with fatty acid-binding protein 4 (FABP4) inhibitors and modified with platelet membranes and investigated its therapeutic role in aged mice. PCBP showed significant maintenance in aged organs and demonstrated excellent biocompatibility. Through cyclic tail vein administration, PCBP extended the lifespan and steadily ameliorated abnormal phenotypes in aged mice, including SASP production, immune and inflammatory status, and age-related metabolic disorders. In senescent ECs, PCBP mediated the activation of vascular endothelial growth factor (VEGF) signaling and glycolysis and inhibition of FABP4 by inducing the synthesis of hypoxia-inducible factor-1α, thereby reawakening neovascularization and restoring glycolipid metabolic homeostasis. In conclusion, the PCBP nanocapsule system provides a promising avenue for interventions against aging-induced dysfunction.

Asunto(s)

Envejecimiento , Nanocápsulas , Animales , Ratones , Envejecimiento/metabolismo , Nanocápsulas/química , Humanos , Ratones Endogámicos C57BL , Glucolípidos/química , Glucolípidos/metabolismo , Senescencia Celular/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Angiogénesis

RESUMEN

The treatment of triple-negative breast cancer (TNBC) faces challenges due to its limited immune response and weak tumor immunogenicity. A collaborative strategy involves combining the activation of pyroptosis and the stimulator of interferon genes (STING) pathway to enhance tumor immunogenicity and fortify the antitumor immune response, which may improve therapeutic outcomes in TNBC. In this study, we report the fabrication of a zinc-phenolic nanocapsule (RMP@Cap), which is loaded with mitoxantrone (MTO) and anti-PD-L1 antibodies (aPD-L1) and coated with erythrocyte membrane, for TNBC immunotherapy. The delivery of RMP@Cap can induce tumor cell pyroptosis and, therefore, trigger the release of mitochondrial DNA, which further combines with zinc agonists to intensify STING activation, resulting in a cascade amplification of the therapeutic effect on tumors. Additionally, the incorporation of aPD-L1 into the zinc-phenolic nanocapsule relieves the inhibitory effect of tumor cells on recruited cytotoxic T cells, thereby improving the tumor-killing capacity. Furthermore, the incorporation of a camouflaged erythrocyte membrane coating enables nanocapsules to achieve prolonged in vivo circulation, resulting in improved tumor accumulation for effective antitumor therapy. This study demonstrates a synergistic therapeutic modality involving pyroptosis, coupled with the simultaneous activation and cyclic amplification of the STING pathway in immunotherapy.

Asunto(s)

Inmunoterapia , Proteínas de la Membrana , Nucleotidiltransferasas , Piroptosis , Piroptosis/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Animales , Ratones , Nucleotidiltransferasas/metabolismo , Humanos , Femenino , Neoplasias de la Mama Triple Negativas/terapia , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Zinc/química , Mitoxantrona/química , Mitoxantrona/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Nanocápsulas/química , Ratones Endogámicos BALB C , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Antígeno B7-H1/metabolismo , Ensayos de Selección de Medicamentos Antitumorales

RESUMEN

OBJECTIVES: Furosemide (FSM), a potent loop diuretic, is used to treat edema due to hypertension, congestive heart failure, and liver and renal failures. FSM applications are limited by its low bioavailability. Our aim is to use different nanoencapsulation strategies to control the release of FSM and enhance its pharmacokinetic properties. METHODS: Two types of FSM-loaded nanocapsules, namely FSM-loaded lipid nanocapsules (LNCs) and polymeric nanocapsules (PNCs), were developed, physicochemically characterized, and subjected to pharmacokinetic and pharmacodynamic studies. Lipid nanocapsules were prepared by the simple phase inversion method using LabrafacTM lipid, while the polymeric nanocapsules were prepared by nanoprecipitation method using polycaprolactone polymer. RESULTS: Transmission electron microscopy ascertains spherical structures, corroborating the nanometric diameter of both types of nanocapsules. The particle size of the optimized FSM-loaded LNCs and FSM-loaded PNCs was 32.19 ± 0.72 nm and 230.7 ± 5.13 nm, respectively. The percent entrapment efficiency was 63.56 ± 1.40% of FSM for the optimized PNCs. The in vitro release study indicated prolonged drug release compared to drug solutions. The two loaded nanocapsules systems succeeded in enhancing the pharmacokinetic parameters in comparison to the marketed FSM solution with superior diuretic activity (p < 0.05). The results of the stability study and the terminal sterilization by autoclave indicated the superiority of LNCs over PNCs in maintaining the physical parameters under storage conditions and the drastic conditions of sterilization. CONCLUSIONS: LNCs and PNCs are considered promising nanosysems for improving the diuretic effect of FSM.

Asunto(s)

Diuréticos , Furosemida , Lípidos , Nanocápsulas , Tamaño de la Partícula , Polímeros , Nanocápsulas/química , Furosemida/administración & dosificación , Furosemida/farmacocinética , Furosemida/química , Furosemida/farmacología , Animales , Diuréticos/administración & dosificación , Diuréticos/farmacocinética , Diuréticos/farmacología , Lípidos/química , Polímeros/química , Ratas , Masculino , Liberación de Fármacos , Administración Intravenosa , Sistemas de Liberación de Medicamentos/métodos , Ratas Wistar , Poliésteres/química , Portadores de Fármacos/química , Disponibilidad Biológica

RESUMEN

Food spoilage exacerbates global hunger and poverty, necessitating urgent advancements in food shelf life extension methodologies. However, balancing antibacterial efficacy for food preservation with human and environmental safety remains a significant challenge. Natural essential oils (EOs), known for their potent antibacterial and antioxidant properties, offer eco-friendly alternatives, yet their high volatility and instability limit practical applications. Herein, we conducted the encapsulation of EOs within biocompatible metal phenolic networks (MPNs) to create EOs@MPN nanocapsules. Subsequently, these nanocapsules were integrated into bio-nanocomposite films composed of natural soy protein isolate (SPI) and carboxymethyl cellulose (CMC). The resulting films exhibited robust mechanical properties (Tensile Strength >10 MPa) and significantly enhanced antioxidant activity (7-fold higher than pure films). Importantly, the synergistic combination of EOs and MPNs conferred enhanced antibacterial efficacy. Safety assessments confirmed the bio-nanocomposite films' high biodegradability (> 90 %) and negligible cytotoxicity, ensuring environmental sustainability and human health safety. In practical applications, the bio-nanocomposite films effectively delayed the surface browning of fresh-cut fruits for up to 48 h, demonstrating a pronounced synergistic antioxidative effect against oxidation. Moreover, tomatoes and blueberries packaged with the bio-nanocomposite films still maintained freshness for up to 12 days, offering promising strategies for extending the shelf life of perishable fruits. These findings underscore the potential of EOs@MPN-based bio-nanocomposite films as sustainable solutions for food preservation and highlight their practical viability in mitigating food spoilage and enhancing food security globally.

Asunto(s)

Antioxidantes , Conservación de Alimentos , Frutas , Nanocápsulas , Nanocompuestos , Aceites Volátiles , Aceites Volátiles/química , Aceites Volátiles/farmacología , Conservación de Alimentos/métodos , Nanocápsulas/química , Nanocompuestos/química , Frutas/química , Antioxidantes/química , Antioxidantes/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Fenoles/química , Metales/química , Humanos

RESUMEN

Nucleic Acid Nanocapsules (NANs) are nucleic acid nanostructures that radially display oligonucleotides on the surface of cross-linked surfactant micelles. Their chemical makeup affords the stimuli-responsive release of therapeutically active DNA-surfactant conjugates into the cells. While NANs have so far demonstrated the effective cytosolic delivery of their nucleic acid cargo, as seen indirectly by their gene regulation capabilities, there remain gaps in the molecular understanding of how this process happens. Herein, we examine the enzymatic degradation of NANs and confirm the identity of the DNA-surfactant conjugates formed by using mass spectrometry (MS). With surface enhanced (resonance) Raman spectroscopy (SE(R)RS), we also provide evidence that the energy-independent translocation of such DNA-surfactant conjugates is contingent upon their release from the NAN structure, which, when intact, otherwise buries the hydrophobic surfactant tail in its interior. Such information suggests a critical role of the surfactant in the lipid disruption capability of the DNA surfactant conjugates generated from degradation of the NANs. Using NANs made with different tail lengths (C12 and C10), we show that this mechanism likely holds true despite significant differences in the physical properties (i.e., critical micelle concentration (CMC), surfactants per micelle, Nagg) of the resultant particles (C12 and C10 NANs). While the total cellular uptake efficiencies of C12 and C10 NANs are similar, there were differences observed in their cellular distribution and localized trafficking, even after ensuring that the total concentration of DNA was the same for both particles. Ultimately, C10 NANs appeared less diffuse within cells and colocalized less with lysosomes over time, achieving more significant knockdown of the target gene investigated, suggesting more effective endosomal escape. These differences indicate that the surfactant assembly and disassembly properties, including the number of surfactants per particle and the CMC can have important implications for the cellular delivery efficacy of DNA micelles and surfactant conjugates.

Asunto(s)

Citosol , ADN , Micelas , Tensoactivos , Tensoactivos/química , ADN/química , ADN/metabolismo , Citosol/metabolismo , Humanos , Nanocápsulas/química

RESUMEN

Diazepam (DZP) is a sedative medication prescribed to treat anxiety and as a sleep inducer, although its residual effects are unfavorable to patients. Nanotechnology represents a tool to improve the pharmacological characteristics of drugs, reducing their side effects. This study aimed to develop and characterize DZP nanocapsules and to evaluate their toxicity in alternative models and the hypnotic-sedative effect in mice. Nanocapsules were prepared by the nanoprecipitation method and properly characterized. Long-term and accelerated stability studies were performed. The in vitro release profile was determined by diffusion in Franz cells. The safety of the formulation was evaluated in the Caenorhabditis elegans (C. elegans) and the oral acute toxicity in mice. Pharmacological evaluation was performed using thiopental-induced sleeping time. DZP was successfully incorporated into Poly-(ɛ-caprolactone) (PCL) nanocapsules, with high entrapment efficiency. The nanocapsule did not affect the development or survival of C. elegans, different from the free drug, which affected the nematode development at the higher tested dose. No signs of toxicity, nor body mass or feed consumption changes were observed during the 14 days evaluated. Finally, this innovative formulation carrying DZP can produce a hypnotic-effect at a reduced dose compared to the free drug, with no toxicity in alternative models.

Asunto(s)

Caenorhabditis elegans , Diazepam , Hipnóticos y Sedantes , Nanocápsulas , Sueño , Animales , Caenorhabditis elegans/efectos de los fármacos , Nanocápsulas/toxicidad , Nanocápsulas/química , Hipnóticos y Sedantes/toxicidad , Hipnóticos y Sedantes/farmacología , Ratones , Diazepam/toxicidad , Diazepam/farmacología , Sueño/efectos de los fármacos , Masculino , Femenino

RESUMEN

Recently, nanocarriers have been utilized for encapsulating and sustained release of agrochemicals specifically auxins. Due to their potential applications such as increased bioavailability and improved crop yield and nutritional quality. Herein, the efficacy of alginate/chitosan nanocapsules as a nanocarrier for the hormone indole-3-butyric acid (IBA) loading and its effect on rooting tobacco plants has been carried out in the present study. The average particle size of IBA-alginate/chitosan nanocapsules was measured by Dynamic light scattering analysis at 321 nm. Scanning electron microscope studies revealed the spherical shape of nanoparticles with an average size of 97 nm. The average particle size of IBA-alginate/chitosan nanocapsules was measured by Dynamic light scattering analysis at 321 nm. The characteristic peaks of IBA on alginate/chitosan nanocapsules were identified by Fourier transform infrared spectroscopic analysis. Also, high efficiency (35%) of IBA hormone loading was observed. The findings indicated that the concentration of 3 mgL-1 of IBA-alginate/chitosan nanocapsules has the highest efficiency in increasing the rooting in tobacco (Nicotiana tabacum) plants compared to other treatments. According to our results, we can introduce alginate/chitosan nanocapsules as an efficient nanocarrier in IBA hormone transfer applications and their use in agriculture.

Asunto(s)

Alginatos , Quitosano , Indoles , Nanocápsulas , Nicotiana , Raíces de Plantas , Quitosano/química , Nicotiana/efectos de los fármacos , Nicotiana/crecimiento & desarrollo , Nicotiana/metabolismo , Alginatos/química , Indoles/química , Nanocápsulas/química , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Tamaño de la Partícula , Espectroscopía Infrarroja por Transformada de Fourier , Ácidos Hexurónicos/química , Ácido Glucurónico/química , Reguladores del Crecimiento de las Plantas/farmacología , Reguladores del Crecimiento de las Plantas/química

RESUMEN

The dense extracellular matrix (ECM) in the tumor microenvironment forms an abnormal physical barrier, which impedes the delivery and penetration of nanomedicines and hinders their therapeutic efficacy. Herein, we synthesize matrix-degrading soft-nanocapsules composed of human serum albumin (HSA) and hyaluronidase (HAase) for overcoming the obstruction of ECM in the tumor microenvironment. The matrix-degrading human serum albumin/hyaluronidase soft-nanocapsules, referred to as HSA/HAase SNCs, possess a uniform diameter, inward hollow structure, and wrinkled morphology. In vitro biocompatibility results indicate that the HSA/HAase SNCs display no adverse effects on the viability of human umbilical vein endothelial cells (HUVECs), smooth muscle cells (SMCs), and mouse breast cancer (4T1) cells and do not induce hemolysis towards red blood cells (RBCs). The HSA/HAase SNCs exhibit a 1.4-fold increase in tumor cellular uptake compared to the stiff-counterparts and enhanced penetration in 4T1-, mouse colon carcinoma 26- (CT26-), and mouse pancreatic cancer- (PanO2-) multicellular spheroids. Thanks to the advanced biological properties, a photodynamic platform prepared by loading Ce6 in the HSA/HAase SNCs (HSA/HAase@Ce6) shows improved reactive oxygen species production, a stronger killing effect for cancer cells, and deeper penetration in tumor tissues. In vivo experiments show that HSA/HAase@Ce6 effectively inhibits tumor growth in breast cancer mouse models. RNA-seq analysis of the mice that received the treatment of HSA/HAase@Ce6 shows enrichment of signaling pathways associated with ECM-degradation, which demonstrates that the matrix-degrading nanocapsules overcome the ECM-induced physical barriers in tumors. Overall, the matrix-degrading soft-nanoplatform represents a highly promising strategy to overcome ECM-induced physical barriers and enhance the therapeutic efficacy of nanomedicines.

Asunto(s)

Neoplasias de la Mama , Hialuronoglucosaminidasa , Fotoquimioterapia , Fármacos Fotosensibilizantes , Animales , Humanos , Ratones , Hialuronoglucosaminidasa/metabolismo , Femenino , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/síntesis química , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Albúmina Sérica Humana/química , Células Endoteliales de la Vena Umbilical Humana , Nanocápsulas/química , Antineoplásicos/química , Antineoplásicos/farmacología , Ratones Endogámicos BALB C , Matriz Extracelular/metabolismo , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral

RESUMEN

Hair follicle-penetrating nanoparticles offer a promising avenue for targeted antibiotic delivery, especially in challenging infections like acne inversa or folliculitis decalvans. However, demonstrating their efficacy with existing preclinical models remains difficult. This study presents an innovative approach using a 3D in vitro organ culture system with human hair follicles to investigate the hypothesis that antibiotic nanocarriers may reach bacteria within the follicular cleft more effectively than free drugs. Living human hair follicles were transplanted into a collagen matrix within a 3D printed polymer scaffold to replicate the follicle's microenvironment. Hair growth kinetics over 7 days resembled those of simple floating cultures. In the 3D model, fluorescent nanoparticles exhibited some penetration into the follicle, not observed in floating cultures. Staphylococcus aureus bacteria displayed similar distribution profiles postinfection of follicles. While rifampicin-loaded lipid nanocapsules were as effective as free rifampicin in floating cultures, only nanoencapsulated rifampicin achieved the same reduction of CFU/mL in the 3D model. This underscores the hair follicle microenvironment's critical role in limiting conventional antibiotic treatment efficacy. By mimicking this microenvironment, the 3D model demonstrates the advantage of topically administered nanocarriers for targeted antibiotic therapy against follicular infections.

Asunto(s)

Antibacterianos , Folículo Piloso , Impresión Tridimensional , Rifampin , Staphylococcus aureus , Folículo Piloso/microbiología , Folículo Piloso/efectos de los fármacos , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Staphylococcus aureus/efectos de los fármacos , Rifampin/farmacología , Rifampin/uso terapéutico , Rifampin/administración & dosificación , Sistemas de Liberación de Medicamentos , Nanopartículas/química , Nanocápsulas/química , Infecciones Estafilocócicas/tratamiento farmacológico

RESUMEN

This study evaluated the effects of topically applied hydrogels (HG) containing nanoencapsulated indol-3-carbinol (I3C) and its free form in a rat model of skin wounds. Formulations were topically applied twice a day for five days to the wounds. On days 1, 3, and 6, the wound area was measured to verify the % of regression. On the sixth day, the animals were euthanized for the analysis of the inflammatory and oxidative profile in wounds. The nanocapsules (NC) exhibited physicochemical characteristics compatible with this kind of suspension. After five hours of exposure to ultraviolet C, more than 78% of I3C content in the suspensions was still observed. The NC-I3C did not modify the physicochemical characteristics of HG when compared to the HG base. In the in vivo study, an increase in the size of the wound was observed on the 3rd experimental day, which was lower in the treated groups (mainly in HG-NC-I3C) compared to the control. On the 6th day, HG-I3C, HG-NC-B, and HG-NC-I3C showed lower regression of the wound compared to the control. Additionally, HG-NC-I3C exhibited an anti-inflammatory effect (as observed by decreased levels of interleukin-1B and myeloperoxidase), reduced oxidative damage (by decreased reactive species, lipid peroxidation, and protein carbonylation levels), and increased antioxidant defense (by improved catalase activity and vitamin C levels) compared to the control. The current study showed more satisfactory results in the HG-NC-I3C group than in the free form of I3C in decreasing acute inflammation and oxidative damage in wounds.

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I3C nanocapsules exhibited characteristics compatible with this kind of suspension;On 3rd day, I3C nanocapsules prevented the increase of wound area;I3C nanocapsules decreased oxidative damage in wound tissue;Inflammatory proteins were decreased in I3C nanocapsules treated group.

Asunto(s)

Indoles , Inflamación , Nanocápsulas , Estrés Oxidativo , Piel , Cicatrización de Heridas , Animales , Indoles/farmacología , Ratas , Cicatrización de Heridas/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Piel/efectos de los fármacos , Piel/patología , Piel/metabolismo , Nanocápsulas/química , Masculino , Ratas Wistar , Antioxidantes/farmacología

RESUMEN

Ferroptosis-mediated multimodal therapy has emerged as a promising strategy for tumor elimination, with lipid peroxide (LPO) playing a pivotal role. However, the therapeutic efficiency is limited due to insufficient intracellular levels of free fatty acids (FFA), which severely hinder the production of LPO. To address this limitation, we proposed a lipophagy strategy aimed at degrading lipid droplets (LDs) to release FFA, serving as the essential "fuel" for LPO production. In this study, the lipophagy inducer epigallocatechin gallate (EGCG) was self-assembled with reactive oxygen species (ROS)-producer phenethyl isothiocyanate (PEITC) mediated by Fe2+ to form EFP nanocapsules, which were further integrated into microneedle patches to form a "all-in-one" EFP@MNs. The metal-polyphenol network structure of EFP endow it with photothermal therapy capacity. Upon insertion into tumors, the released EFP nanocapsules were demonstrated to induce lipophagy through metabolic disturbance, thereby promoting LPO production and facilitating ferroptosis. When combined with photothermal therapy, this approach significantly remolded the tumor immune microenvironment by driving tumor-associated macrophages toward M1 phenotype and enhancing dendritic cell maturation. Encouragingly, in conjunction with αPD-L1 treatment, the proposed EFP@MNs exhibited remarkable efficacy in tumor ablation. Our study presents a versatile framework for utilizing microneedle patches to power ferroptosis-mediated multimodal therapy.

Asunto(s)

Ferroptosis , Nanocápsulas , Polifenoles , Ferroptosis/efectos de los fármacos , Animales , Polifenoles/administración & dosificación , Polifenoles/química , Nanocápsulas/química , Ratones , Catequina/administración & dosificación , Catequina/análogos & derivados , Agujas , Humanos , Línea Celular Tumoral , Terapia Fototérmica/métodos , Terapia Combinada , Femenino , Ratones Endogámicos BALB C , Especies Reactivas de Oxígeno/metabolismo , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Microambiente Tumoral/efectos de los fármacos , Autofagia/efectos de los fármacos , Peróxidos Lipídicos/metabolismo , Isotiocianatos

RESUMEN

Hibiscus sabdariffa L. (roselle) is a medicinal and edible plant which rich in anthocyanins with potent antioxidant properties. To enhance the stability of roselle anthocyanins, they were encapsulated in nanocapsules composed of carboxymethyl chitosan (CMC), chitosan hydrochloride (CHC), and ß-lactoglobulin (ß-Lg). In vitro simulated digestion assays evaluated the impact of various core-to-wall ratios and ß-Lg concentrations on the bioaccessibility of seven anthocyanins. Nanocapsules with a core-to-wall ratio of 1:2 and ß-Lg at 10 mg/mL exhibited the highest encapsulation efficiency (EE). Cyanidin-3-glucoside had the highest EE, while cyanidin-3-sambubioside showed the outstanding retention rate. Furthermore, simulated digestion experiments combined with molecular docking revealed that peonidin-3-glucoside and petunidin-3-glucoside likely interact with and bind to the outer ß-Lg layer of the nanocapsules, increasing their release during in vitro digestion. This study demonstrates that encapsulating roselle anthocyanins in CMC, CHC, and ß-Lg nanocapsules significantly enhances their bioaccessibility.

Asunto(s)

Antocianinas , Hibiscus , Nanocápsulas , Extractos Vegetales , Antocianinas/química , Hibiscus/química , Nanocápsulas/química , Extractos Vegetales/química , Digestión , Composición de Medicamentos , Simulación del Acoplamiento Molecular , Humanos , Disponibilidad Biológica

RESUMEN

Curcumin (Cur) as a natural food additive and photosensitizer has been widely applied on photodynamic sterilization and preservation for food, but the poor aqueous solubility and light stability restrict its extensive application. In this study, we report a Cur nanocapsules (Cur-CDs) made by carbon dots (CDs). Attributing to the hydrogen bonds formed between Cur and CDs, Cur-CDs exhibits excellent Cur aqueous solubility each to 9286.98 ng/mL (enhanced by 246.27 times) and light stability (enhanced by 1.51 times). The photogenerated electron transmission from Cur to CDs in addition resulted in >1.23 and 1.60 times generation of •O2- and •OH, compared to that of bare Cur. Accordingly, 5.73 × 103 CFU L. monocytogenes, and 5.43 × 103 CFU S. aureus were killed by 0.06 mg/mL Cur-CDs within 20 mins of blue light, showing the promising potential in the development and application of safe and environmentally friendly non-thermal sterilization technology based on Cur-CDs.

Asunto(s)

Carbono , Curcumina , Listeria monocytogenes , Nanocápsulas , Fármacos Fotosensibilizantes , Puntos Cuánticos , Staphylococcus aureus , Listeria monocytogenes/efectos de los fármacos , Listeria monocytogenes/crecimiento & desarrollo , Listeria monocytogenes/efectos de la radiación , Curcumina/farmacología , Curcumina/química , Carbono/química , Carbono/farmacología , Staphylococcus aureus/efectos de los fármacos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Puntos Cuánticos/química , Nanocápsulas/química , Esterilización , Antibacterianos/farmacología , Antibacterianos/química , Luz

RESUMEN

In this study, the effect of Thymus vulgaris essential oil (TVO) nanoemulsion (NE, 500 mg/L) in combination with ultrasound (ultrasound-NE) on the microbial and physiological quality of green bell pepper was investigated. The TVO-NE droplet size and zeta potential were 84.26 nm and - 0.77 mV, respectively. The minimum inhibitory concentrations of the TVO and TVO-NE against E. coli and S. aureus were about 0.07 and 7 g/L, respectively. The NE-ultrasound treatment exhibited the lowest peroxidase activity and respiration rate with no detrimental effect on texture, total phenolic content, antioxidant activity, pH, and TSS. Although the NE-ultrasound treatment showed the highest weight loss and electrolytic leakage, it exhibited the best visual color and appearance. The NE-ultrasound treatment descended the total viable/mold and yeast counts significantly compared to control. Results showed that treating the bell peppers with NE-ultrasound can result in bell peppers with good postharvest quality and extended shelf life.

Asunto(s)

Capsicum , Escherichia coli , Nanocápsulas , Aceites Volátiles , Staphylococcus aureus , Thymus (Planta) , Thymus (Planta)/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Capsicum/química , Capsicum/microbiología , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Conservación de Alimentos/métodos , Ultrasonido/métodos , Antioxidantes/farmacología , Ondas Ultrasónicas , Emulsiones

RESUMEN

Leukemia, particularly acute myeloid leukemia (AML) is considered a serious health condition with high prevalence among adults. Accordingly, finding new therapeutic modalities for AML is urgently needed. This study aimed to develop a biocompatible nanoformulation for effective oral delivery of the phytomedicine; baicalin (BAC) for AML treatment. Lipid nanocapsules (LNCs) based on bioactive natural components; rhamnolipids (RL) as a biosurfactant and the essential oil linalool (LIN), were prepared using a simple phase-inversion method. The elaborated BAC-LNCs displayed 61.1 nm diameter and 0.2 PDI. Entrapment efficiency exceeded 98 % with slow drug release and high storage-stability over 3 months. Moreover, BAC-LNCs enhanced BAC oral bioavailability by 2.3-fold compared to BAC suspension in rats with higher half-life and mean residence-time. In vitro anticancer studies confirmed the prominent cytotoxicity of BAC-LNCs on the human leukemia monocytes (THP-1). BAC-LNCs exerted higher cellular association, apoptotic capability and antiproliferative activity with DNA synthesis-phase arrest. Finally, a mechanistic study performed through evaluation of various tumor biomarkers revealed that BAC-LNCs downregulated the angiogenic marker, vascular endothelial growth-factor (VEGF) and the anti-apoptotic marker (BCl-2) and upregulated the apoptotic markers (Caspase-3 and BAX). The improved efficacy of BAC bioactive-LNCs substantially recommends their pharmacotherapeutic potential as a promising nanoplatform for AML treatment.

Asunto(s)

Liberación de Fármacos , Flavonoides , Leucemia Mieloide Aguda , Nanocápsulas , Animales , Flavonoides/farmacología , Flavonoides/administración & dosificación , Flavonoides/química , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Nanocápsulas/química , Masculino , Apoptosis/efectos de los fármacos , Ratas , Glucolípidos/química , Glucolípidos/administración & dosificación , Glucolípidos/farmacología , Monoterpenos/farmacología , Monoterpenos/química , Monoterpenos/administración & dosificación , Células THP-1 , Disponibilidad Biológica , Administración Oral , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/química , Ratas Sprague-Dawley , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Monoterpenos Acíclicos

RESUMEN

Despite the potential of photodynamic therapy (PDT) in cancer treatment, the development of efficient and photostable photosensitizing molecules that operate at long wavelengths of light has become a major hurdle. Here, we report for the first time an Ir(III)-phthalocyanine conjugate (Ir-ZnPc) as a novel photosensitizer for high-efficiency synergistic PDT treatment that takes advantage of the long-wavelength excitation and near infrared (NIR) emission of the phthalocyanine scaffold and the known photostability and high phototoxicity of cyclometalated Ir(III) complexes. In order to increase water solubility and cell membrane permeability, the conjugate and parent zinc phthalocyanine (ZnPc) were encapsulated in amphoteric redox-responsive polyurethane-polyurea hybrid nanocapsules (Ir-ZnPc-NCs and ZnPc-NCs, respectively). Photobiological evaluations revealed that the encapsulated Ir-ZnPc conjugate achieved high photocytotoxicity in both normoxic and hypoxic conditions under 630 nm light irradiation, which can be attributed to dual Type I and Type II reactive oxygen species (ROS) photogeneration. Interestingly, PDT treatments with Ir-ZnPc-NCs and ZnPc-NCs significantly inhibited the growth of three-dimensional (3D) multicellular tumor spheroids. Overall, the nanoencapsulation of Zn phthalocyanines conjugated to cyclometalated Ir(III) complexes provides a new strategy for obtaining photostable and biocompatible red-light-activated nano-PDT agents with efficient performance under challenging hypoxic environments, thus offering new therapeutic opportunities for cancer treatment.

Asunto(s)

Antineoplásicos , Indoles , Isoindoles , Fotoquimioterapia , Fármacos Fotosensibilizantes , Humanos , Indoles/química , Indoles/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Iridio/química , Iridio/farmacología , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Compuestos de Zinc/química , Especies Reactivas de Oxígeno/metabolismo , Nanocápsulas/química , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos

RESUMEN

A novel nano bio-fertilizer encapsulation method was developed to crosslink chitosan and alginate with humic acid. These nanocapsules, referred to as (Ch./Alg.HA.NPK) or (Ch./Alg.HA.NPK.PGPRs), were loaded with nanoscale essential agro-nutrients (NPK) and beneficial microorganisms Pseudomonas Fluorescence abbreviated as (P.Fluorescence). Structural and morphological analyses were conducted using FourierTransform Infrared, Thermogravimetric Analysis, Scanning Electron Microscopy, Malvern Zeta NanoSizer, and Zeta potential. Encapsulation efficiency and water retention were also determined compared to control non-crosslinked nanocapsules. The sustained cumulative release of NPK over 30 days was also investigated to 33.2%, 47.8%, and 68.3%, alternatively. The release mechanism, also assessed through the kinetic module of the Korsemeyer- Peppas Mathematical model, demonstrated superior performance compared to non-crosslinked nanocapsules (chitosan/alginate). These results show the potential of the synthesized nanocapsules for environmentally conscious controlled release of NPK and PGPRs, thereby mitigating environmental impact, enhancing plant growth, and reducing reliance on conventional agrochemical fertilizers.

Asunto(s)

Agricultura , Alginatos , Quitosano , Fertilizantes , Quitosano/química , Agricultura/métodos , Alginatos/química , Nanocápsulas/química , Sustancias Húmicas/análisis , Pseudomonas/metabolismo , Pseudomonas/crecimiento & desarrollo

RESUMEN

The use of essential oils as natural antioxidant, antimicrobial and insect repellent agent was limited by the loss of bioactive components especially volatile compounds. This study aimed to improve biological properties of curry leaf essential oil (CLEO) by producing nanometer sized particles through two different synthesis techniques; nanoencapsulation and nanoprecipitation. The methods produced different nanostructures; nanocapsules and nanospheres distinguished by the morphological structure (TEM analysis). Successful loading of CLEO into chitosan nanocarrier was proven by FTIR spectra. Zeta potential values for both nanostructures were more than +30 mV implying their stability against aggregation. CLEO loaded nanocapsules exhibited highest antibacterial properties against Gram-positive bacteria compared to nanospheres. Meanwhile, CLEO loaded nanospheres recorded up until 90.44 % DPPH radical scavenging properties, higher compared to nanocapsules. Both nanostructures demonstrated further improvement in antioxidant and antibacterial activities with the incorporation of higher chitosan concentration. In vitro release analysis indicated that CLEO undergo two-stage discharge mechanism where fast discharge occurred up until 12 h followed by sustained released afterwards. The two synthesis methods applied synergistically with greater chitosan concentration successfully produced nanostructures with >60 % encapsulation efficiency (EE). This concluded that both techniques were reliable to protect the bioactive constituents of CLEO for further used.

Asunto(s)

Antibacterianos , Antioxidantes , Quitosano , Liberación de Fármacos , Nanopartículas , Aceites Volátiles , Hojas de la Planta , Quitosano/química , Quitosano/farmacología , Aceites Volátiles/química , Aceites Volátiles/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Hojas de la Planta/química , Antioxidantes/química , Antioxidantes/farmacología , Nanopartículas/química , Fenómenos Químicos , Pruebas de Sensibilidad Microbiana , Portadores de Fármacos/química , Tamaño de la Partícula , Nanocápsulas/química