Search Results (10)

Background/Objectives: Over the past 25 years, numerous biological molecules, like recombinant lysosomal enzymes, neurotrophins, receptors, and therapeutic antibodies, have been tested in clinical trials for neurological diseases. However, achieving significant success in clinical applications has remained elusive. A primary challenge has been the inability of these molecules to traverse the blood–brain barrier (BBB). Recognizing this hurdle, our study aimed to utilize niosomes as delivery vehicles, leveraging the “molecular Trojan horse” technology, to enhance the transport of molecules across the BBB. Methods: Previously synthesized memantine derivatives (MP1–4) were encapsulated into niosomes for improved BBB permeability, hypothesizing that this approach could minimize peripheral drug toxicity while ensuring targeted brain delivery. Using the human neuroblastoma (SH-SY5Y) cell line differentiated into neuron-like structures with retinoic acid and then exposed to amyloid beta 1–42 peptide, we established an in vitro Alzheimer’s disease (AD) model. In this model, the potential usability of MP1–4 was assessed through viability tests (MTT) and toxicological response analysis. The niosomes’ particle size and morphological structures were characterized using scanning electron microscopy (SEM), with their loading and release capacities determined via UV spectroscopy. Crucially, the ability of the niosomes to cross the BBB and their potential anti-Alzheimer efficacy were analyzed in an in vitro transwell system with endothelial cells. Results: The niosomal formulations demonstrated effective drug encapsulation (encapsulation efficiency: 85.3% ± 2.7%), controlled release (72 h release: 38.5% ± 1.2%), and stable morphology (PDI: 0.22 ± 0.03, zeta potential: −31.4 ± 1.5 mV). Among the derivatives, MP1, MP2, and MP4 exhibited significant neuroprotective effects, enhancing cell viability by approximately 40% (p < 0.05) in the presence of Aβ1-42 at a concentration of 47 µg/mL. The niosomal delivery system improved BBB permeability by 2.5-fold compared to free drug derivatives, as confirmed using an in vitro bEnd.3 cell model. Conclusions: Memantine-loaded niosomes provide a promising platform for overcoming BBB limitations and enhancing the therapeutic efficacy of Alzheimer’s disease treatments. This study highlights the potential of nanotechnology-based delivery systems in developing targeted therapies for neurodegenerative diseases. Further in vivo studies are warranted to validate these findings and explore clinical applications. Full article

The recently demonstrated concept of the plasma photocathode, whereby a high-brightness bunch is initialized by laser ionization within a plasma wakefield acceleration bubble, is informally referred to as Trojan Horse wakefield acceleration. In a similar vein, the dielectric Trojan Horse concept incorporates a dielectric-lined waveguide to support a charged particle beam-driven accelerating mode and uses laser initiated ionization of neutral gas within the waveguide to generate a witness beam. One of the advantages of the dielectric Trojan Horse concept is the reduced requirements in terms of timing precision due to operation at a lower frequency. In this paper, we present experimental results on the generation and characterization of a four-bunch drive train for resonant excitation of wakefields in a cylindrical dielectric waveguide conducted at the Argonne Wakefield Accelerator facility. The results lay the foundation for the demonstration of a plasma photocathode scheme within a dielectric wakefield accelerating structure. Modifications to improve capture efficiency with improved beam transmission are suggested as well. Full article

Macrophages, which are part of the mononuclear phagocytic system, possess sensory receptors that enable them to target cancer cells. In addition, they are able to engulf large amounts of particles through phagocytosis, suggesting a potential “Trojan horse” drug delivery approach to tumors by facilitating the engulfment of drug-hidden particles by macrophages. Recent research has focused on the development of macrophage-based microrobots for anticancer therapy, showing promising results and potential for clinical applications. In this review, we summarize the recent development of macrophage-based microrobot research for anticancer therapy. First, we discuss the types of macrophage cells used in the development of these microrobots, the common payloads they carry, and various targeting strategies utilized to guide the microrobots to cancer sites, such as biological, chemical, acoustic, and magnetic actuations. Subsequently, we analyze the applications of these microrobots in different cancer treatment modalities, including photothermal therapy, chemotherapy, immunotherapy, and various synergistic combination therapies. Finally, we present future outlooks for the development of macrophage-based microrobots. Full article

The bile acid transport system is a natural physiological cycling process between the liver and the small intestine, occurring approximately 6–15 times during the day. There are various bile acid transporter proteins on hepatocytes that specifically recognize bile acids for transport. Therefore, in this paper, a novel liposome, cholic acid-modified irinotecan hydrochloride liposomes (named CA-CPT-11-Lip), was prepared based on the “Trojan horse” strategy. The liposomes preparation process was optimized, and some important quality indicators were investigated. The distribution of irinotecan hydrochloride in mice was then analyzed by high-performance liquid chromatography (HPLC), and the toxicity of liposomes to hepatocellular carcinoma cells (HepG-2) was evaluated in vitro. As a result, CA-CPT-11-Lip was successfully prepared. It was spherical with a particle size of 154.16 ± 4.92 nm, and the drug loading and encapsulation efficiency were 3.72 ± 0.04% and 82.04 ± 1.38%, respectively. Compared with the conventional liposomes (without cholic acid modification, named CPT-11-Lip), CA-CPT-11-Lip had a smaller particle size and higher encapsulation efficiency, and the drug accumulation in the liver was more efficient, enhancing the anti-hepatocellular carcinoma activity of irinotecan hydrochloride. The novel nanoliposome modified by cholic acid may help to expand the application of irinotecan hydrochloride in the treatment of hepatocellular carcinoma and construct the drug delivery system mode of drug liver targeting. Full article

A facile and robust microfluidic method to produce nanoparticle-in-microparticle systems (Trojan systems) is reported as a delivery vector for the oral administration of active pharmaceutical ingredients. The microfluidic system is based on two coaxial capillaries that produce monodisperse water-in-oil-in-water (W/O/W) double emulsions in a highly controlled fashion with precise control over the resulting particle structure, including the core and shell dimensions. The influence of the three phase flow rates, pH and drying process on the formation and overall size is evaluated. These droplets are then used as templates for the production of pH-sensitive Trojan microparticles after solvent evaporation. The shell of Trojan microparticles is made of Eudragit^®, a methacrylic acid-ethyl acrylate copolymer that would enable the Trojan microparticle payload to first pass through the stomach without being degraded and then dissolve in the intestinal fluid, releasing the inner payload. The synthesis of the pH-sensitive Trojan microparticles was also compared with a conventional batch production method. The payloads considered in this work were different in nature: (1) fluorescein, to validate the feasibility of the polymeric shell to protect the payload under gastric pH; (2) poly(D,L-lactic acid/glycolic acid)-PLGA nanoparticles loaded with the antibiotic rifampicin. These PLGA nanoparticles were produced also using a microfluidic continuous process and (3) PLGA nanoparticles loaded with Au nanoparticles to trace the PLGA formulation under different environments (gastric and intestinal), and to assess whether active pharmaceutical ingredient (API) encapsulation in PLGA is due efficiently. We further showed that Trojan microparticles released the embedded PLGA nanoparticles in contact with suitable media, as confirmed by electron microscopy. Finally, the results show the possibility of developing Trojan microparticles in a continuous manner with the ability to deliver therapeutic nanoparticles in the gastrointestinal tract. Full article

The investigation of the combined toxic action of different types of nanoparticles (NPs) and their interaction between each other and with aquatic organisms is an important problem of modern ecotoxicology. In this study, we assessed the individual and mixture toxicities of cadmium and zinc sulfides (CdS and ZnS), titanium dioxide (TiO₂), and two types of mesoporous silicon dioxide (with no inclusions (SMB3) and with metal inclusions (SMB24)) by a microalga growth inhibition bioassay. The counting and size measurement of microalga cells and NPs were performed by flow cytometry. The biochemical endpoints were measured by a UV-VIS microplate spectrophotometer. The highest toxicity was observed for SMB24 (EC50, 3.6 mg/L) and CdS (EC50, 21.3 mg/L). A combined toxicity bioassay demonstrated that TiO₂ and the SMB3 NPs had a synergistic toxic effect in combinations with all the tested samples except SMB24, probably caused by a “Trojan horse effect”. Sample SMB24 had antagonistic toxic action with CdS and ZnS, which was probably caused by metal ion scavenging. Full article

The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a “Trojan horse” for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed. Full article

Oropouche orthobunyavirus (OROV) is an emerging arbovirus with a high potential of dissemination in America. Little is known about the role of peripheral blood mononuclear cells (PBMC) response during OROV infection in humans. Thus, to evaluate human leukocytes susceptibility, permissiveness and immune response during OROV infection, we applied RNA hybridization, qRT-PCR and cell-based assays to quantify viral antigens, genome, antigenome and gene expression in different cells. First, we observed OROV replication in human leukocytes lineages as THP-1 monocytes, Jeko-1 B cells and Jurkat T cells. Interestingly, cell viability and viral particle detection are maintained in these cells, even after successive passages. PBMCs from healthy donors were susceptible but the infection was not productive, since neither antigenome nor infectious particle was found in the supernatant of infected PBMCs. In fact, only viral antigens and small quantities of OROV genome were detected at 24 hpi in lymphocytes, monocytes and CD11c⁺ cells. Finally, activation of the Interferon (IFN) response was essential to restrict OROV replication in human PBMCs. Increased expression of type I/III IFNs, ISGs and inflammatory cytokines was detected in the first 24 hpi and viral replication was re-established after blocking IFNAR or treating cells with glucocorticoid. Thus, in short, our results show OROV is able to infect and remain in low titers in human T cells, monocytes, DCs and B cells as a consequence of an effective IFN response after infection, indicating the possibility of leukocytes serving as a trojan horse in specific microenvironments during immunosuppression. Full article

The toxicity of the copper oxide nanoparticles (CuO NP) has been attributed to the so-called “Trojan horse”-type mechanism, relying on the particle uptake and extensive intracellular release of copper ions, due to acidic pH in the lysosomes. Nevertheless, a clear distinction between extra- and intracellular-mediated effects is still missing. Therefore, the impact of the endocytosis inhibitor hydroxy-dynasore (OH-dyn), as well as bafilomycin A1 (bafA1), inhibiting the vacuolar type H⁺-ATPase (V-ATPase), on the cellular toxicity of nano- and microsized CuO particles, was investigated in BEAS 2 B cells. Selected endpoints were cytotoxicity, copper uptake, glutathione (GSH) levels, and the transcriptional DNA damage and (oxidative) stress response using the high-throughput reverse transcription quantitative polymerase chain reaction (RT-qPCR). OH-dyn markedly reduced intracellular copper accumulation in the cases of CuO NP and CuO MP; the modulation of gene expression, induced by both particle types affecting especially HMOX1, HSPA1A, MT1X, SCL30A1, IL8 and GADD45A, were completely abolished. BafA1 lowered the intracellular copper concentration in case of CuO NP and strongly reduced transcriptional changes, while any CuO MP-mediated effects were not affected by bafA1. In conclusion, the toxicity of CuO NP depended almost exclusively upon dynamin-dependent endocytosis and the intracellular release of redox-active copper ions due to lysosomal acidification, while particle interactions with cellular membranes appeared to be not relevant. Full article

Fundamental similarities and differences between laser-driven plasma wakefield acceleration (LWFA) and particle-driven plasma wakefield acceleration (PWFA) are discussed. The complementary features enable the conception and development of novel hybrid plasma accelerators, which allow previously not accessible compact solutions for high quality electron bunch generation and arising applications. Very high energy gains can be realized by electron beam drivers even in single stages because PWFA is practically dephasing-free and not diffraction-limited. These electron driver beams for PWFA in turn can be produced in compact LWFA stages. In various hybrid approaches, these PWFA systems can be spiked with ionizing laser pulses to realize tunable and high-quality electron sources via optical density downramp injection (also known as plasma torch) or plasma photocathodes (also known as Trojan Horse) and via wakefield-induced injection (also known as WII). These hybrids can act as beam energy, brightness and quality transformers, and partially have built-in stabilizing features. They thus offer compact pathways towards beams with unprecedented emittance and brightness, which may have transformative impact for light sources and photon science applications. Furthermore, they allow the study of PWFA-specific challenges in compact setups in addition to large linac-based facilities, such as fundamental beam–plasma interaction physics, to develop novel diagnostics, and to develop contributions such as ultralow emittance test beams or other building blocks and schemes which support future plasma-based collider concepts. Full article