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.

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.

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.

The development of nanovaccines capable of eliciting tumor-specific immune responses holds significant promise for tumor immunotherapy. However, many nanovaccine designs rely heavily on incorporating multiple adjuvants and carriers, increasing the biological hazards associated with these additional components. Here, this work introduces novel flexible nanocapsules (OVAnano) designed to mimic extracellular vesicles, primarily using the ovalbumin antigen and minimal polyethylenimine adjuvant components. These results show that the biomimetic flexible structure of OVAnano facilitates enhanced antigen uptake by dendritic cells (DCs), leading to efficient antigen and adjuvant release into the cytosol via endosomal escape, and ultimately, successful antigen cross-presentation by DCs. Furthermore, OVAnano modulates the intracellular nuclear factor kappa-B (NF-κB) signaling pathway, promoting DC maturation. The highly purified antigens in OVAnano demonstrate remarkable antigen-specific immunogenicity, triggering strong antitumor immune responses mediated by DCs. Therapeutic tumor vaccination studies have also shown that OVAnano administration effectively suppresses tumor growth in mice by inducing immune responses from CD8+ and CD4+ T cells targeting specific antigens, reducing immunosuppression by regulatory T cells, and boosting the populations of effector memory T cells. These findings underscore that the simple yet potent strategy of employing minimal flexible nanocapsules markedly enhances DC-mediated antitumor immunotherapy, offering promising avenues for future clinical applications.

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.

Polymer nanocapsules with hydrophobic cores are promising candidates for nanoreactors to carry out (bio)chemical reactions mimicking the performance of natural cellular systems. Their architecture allows reagents to be encapsulated in the cores enabling reactions to proceed in confined environments in a controlled, and efficient manner. Polysaccharide-shell oil-core nanocapsules are proposed here as facile mergeable nanoreactors. Spontaneous fusion of oppositely charged polysaccharide capsules is demonstrated for the first time. Such capsules are formed and easily loaded with reagents by nanoemulsification of an aqueous solution of hydrophobically modified polysaccharides (chitosan, hyaluronate) and oleic acid with dissolved desired hydrophobic compounds. Efficient fusion of the formed nanocapsules dispersed in an aqueous medium at optimized conditions (pH, ionic strength) is followed using fluorescence microscopy by labeling both their cores and shells with fluorescent dyes. As a proof of concept, a model fluorogenic synthesis is also realized by fusing the capsules containing separated reagents and the catalyst. The nanocapsules and fusion process developed here establish a platform for realization of versatile reactions in a confined environment including model studies on biologically relevant processes taking place in natural systems.

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.

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.

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.

For decades, animal models have been the standard approach in drug research and development, as they are required by regulations in the transition from preclinical to clinical trials. However, there is growing ethical and scientific concern regarding these trials, as 80 % of the therapeutic potential observed in pre-clinical studies are often unable to be replicated, despite demonstrating efficacy and safety. In response to this, Tissue Engineering has emerged as a promising alternative that enables the treatment of various diseases through the production of biological models for advanced biological assays or through the direct development of tissue repairs or replacements. One of the promising applications of Tissue Engineering is the development of three-dimensional (3D) models for in vitro tests, replacing the need for in vivo animal models. In this study, 3D skin equivalents (TSE) were produced and used as an in vitro model to test photobiostimulation using curcumin-loaded nanocapsules. Photodynamic biostimulation therapy uses photodynamic processes to generate small amounts of reactive oxygen species (ROS), which can activate important biological effects such as cell differentiation, modulation of inflammatory processes and contribution to cell regeneration. The PLGA nanocapsules (NC) used in the study were synthesized through a preformed polymer deposition method, exhibiting particle size <200 nm, Zeta potential >|30| and polydispersity index between 0.5 and 0.3. Atomic force microscopy analyzes confirmed that the particle size was <200 nm, with a spherical morphology and a predominantly smooth and uniform surface. The NC biocompatibility assay did not demonstrate cytotoxicity for the concentrations tested (2.5-25 μg mL-1).The in vitro release assay showed a slow and sustained release characteristic of the nanocapsules, and cellular uptake assays indicated a significant increase in cellular internalization of the curcumin-loaded nanostructure. Monolayer photobiostimulation studies revealed an increase in cell viability of the HDFn cell line (viability 134 %-228 %) for all LED fluences employed at λ = 450 nm (150, 300, and 450 mJ cm-2). Additionally, the scratch assays, monitoring in vitro scar injury, demonstrated more effective effects on cell proliferation with the fluence of 300 mJ cm-2. Staining of TSE with hematoxylin and eosin showed the presence of cells with different morphologies, confirming the presence of fibroblasts and keratinocytes. Immunohistochemistry using KI-67 revealed the presence of proliferating cells in TSE after irradiation with LED λ = 450 nm (150, 300, and 450 mJ cm-2).