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NANO-SYNBIOTICS: REPROGRAMMING THE GUT MICROBIOME FOR PERSONALIZED SYSTEMIC HEALTH

Introduction: The gut microbiota is a key player in systemic health, modulating immune responses, metabolic pathways, and neural communication by way of the gut–brain, gut–immune, and gut–metabolic axes. Synbiotics, a combination of probiotics and prebiotics, provide synergistic advantages in re-establishing microbial balance. Their therapeutic promise, however, is jeopardized by limitations such as poor survival of probiotics across the gastrointestinal (GI) tract, poor bioavailability, and non-specific release. Nanotechnology introduces a new way to address these barriers and allow for targeted and controlled delivery of bioactive compounds.

Methods: This study reviews recent advances in the exciting fields of nano-encapsulation and nano-carrier-mediated delivery of prebiotics and probiotics in the context of the newly coined word "synbiotics". The different types of nanocarriers have been designed to co-encapsulate prebiotics with probiotics, including polymeric nanoparticles (PLGAs), liposomes, nanogels, and solid lipid nanoparticles (SLNs). This study involves mechanisms to mitigate protection against gastric degradation, reasons for delivery at sites based on intestinal pH or microbial enzymatic sites, and provides a means of promoting colonization. We also examine the roles of microbiome sequencing and artificial intelligence (AI) in the customization of any nano-synbiotic formulation.

Results: Nano-synbiotics exhibited enhanced stabillity in the gastrointestinal tract, intestinal target release, and SCFA production, which ultimately resulted in improved gut colonization and systemic effects. Preclinical and early clinical evidence supports their use in the context of metabolic disease (e.g. obesity, type 2 diabetes), neurodegenerative disease (via the gut–brain axis), and inflammatory bowel disease (IBD). Personalized treatments based on the host microbiome profile and AI-aided analytics further augment their therapeutic value.

Conclusions: Nano-synbiotics provides personalized therapy, allowing gut microbiota modulation for systemic and personalized health interventions. The convergence of nanotechnology and microbiomics opens the door to next-generation biotherapeutics for addressing complex chronic diseases via the gut–systemic axis.

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Changes in Bovine Serum Albumin (BSA) conformation in the presence of silver nanoparticles (AgNPs)
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Blood proteins are the first biological components to interact with a material when it is introduced into an organism. Any alteration in the three-dimensional structure of these proteins can compromise their function. Moreover, the biological response to a material is significantly influenced by protein adsorption—not only in terms of the amount but also the type and structural conformation of the proteins involved [1].

Silver nanoparticles (AgNPs), on the other hand, are biomaterials with promising properties for medical applications. Motivated by this, we set out to study the behavior of a system composed of bovine serum albumin (BSA) and AgNPs.

In this work, we employed density and speed-of-sound measurements to calculate specific volume and adiabatic compressibility. In parallel, we used dynamic light scattering (DLS) and fluorescence spectroscopy to gain insights into protein conformation. The combined data suggest the presence of a balance between metal-enhanced fluorescence (MEF) and surface energy transfer (SET) effects—both dependent on the distance between tryptophan (Trp) residues and the AgNPs [2].

Volumetric and compressibility analyses also revealed changes in the protein’s tertiary structure [3]. DLS results exhibited two distinct peaks: the first corresponding to BSA monomers in their native state and the second to larger aggregates, clearly indicating protein aggregation [4].

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The Development of a Sustainable 3D-Hydrogel System for the Targeted Delivery of EOs extracted from wild bilberry (Vaccinium myrtillus L.) leaves

The 3D-PHydrogel project aims to develop a next-generation, sustainable hydrogel system that is 3D-printed and designed for the intelligent and targeted delivery of bioactive compounds derived from natural plant sources. The core innovation lies in incorporating essential oils (EOs) extracted via green technologies from wild bilberry (Vaccinium myrtillus L.) leaves collected from two regions in Cluj (Transylvania, Romania). These EOs will be embedded into biopolymer matrices composed of renewable resources such as starch (proso millet) and algae-derived materials (alginate). Using ionotropic gelation—a mild, environmentally friendly crosslinking technique—the 3D-PHydrogel project will focus on obtaining a biocompatible 3D hydrogel network capable of encapsulating and gradually releasing active compounds. This system could overcome current challenges related to compound stability, targeted delivery, and controlled release, particularly relevant for nanomedicine and bionanotechnology applications. The 3D-PHydrogel project will drive research combining sustainable and renewable materials available in natural and bioactive resources. Future validation of hydrogel’s functionality will be performed through in vitro assessments of antioxidant, antibacterial, and antifungal potential. The ultimate goal is to contribute to an eco-friendly, functional delivery platform for therapeutic and biomedical use.

Acknowledgement: This work is supported by a grant from the Romanian Ministry of Education and Research, CCCDI-UEFISCDI, project number PN-IV-P1-PCE-2023-1092.

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QUANTITATIVE ANALYSIS OF MAGNETIC NANOPARTICLE CLUSTERS IN A BREAST PHANTOM WITH TUMOR CELLS UNDER A STATIC MAGNETIC FIELD
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Introduction: Despite the growing interest in the medical applications of magnetic nanoparticles (MNPs), the structural changes of MNP clusters in biological media under static magnetic fields (SMFs) remain poorly characterized. This study investigates how SMF influences the density and shape of MNP clusters in a breast phantom containing tumor cells.

Materials and Methods: Fe3O4 nanoparticles (<50 nm, Sigma-Aldrich) with a magnetic moment of 56.31 emu/g, coercivity of 6.48 Oe, and hysteresis loop area of 350.95 erg/g were visualized in a gelatin-based breast-mimicking phantom with MCF-7 breast adenocarcinoma cells in Dulbecco’s Modified Eagle Medium (DMEM, Sigma) using digital breast tomosynthesis. A Nd2Fe14B disc magnet was used to guide MNP distribution, generating mechanical forces on MCF-7 cells. Quantitative analysis of MNP clusters employed the convex hull method to calculate pixel density and circularity in acquired 3D X-ray images using ImageJ 1.53k (NIH) software.

Results: SMF application increased MNP cluster density from 0.28 ± 0.03 pixel-1 to 0.53 ± 0.04 pixel-1 (p < 0.05). There was a 14% increase in the circularity of MNP cluster formations in response to SMF (0.81 ± 0.02 a.u.) compared with MNPs alone (0.70 ± 0.02), p < 0.05. Estimated magnetic forces ranged from 0.001 to 255.28 pN, which was within the range known to initiate magneto-mechanochemical effects on tumor cells. Remote control of MNP clustering by SMF leads to altered force distributions in the cells, modulating mechanochemical transduction via conformational changes in protein–lipid interactions, ion channels and membrane receptors. This enables theranostic applications, wherein SMFs enhance MNP delivery, imaging contrast, and targeted antitumor effects.

Conclusion: The current study demonstrates that SMF influences the spatial distribution of MNP clusters in a breast phantom with MCF-7 cells, drawing attention to personalized breast cancer treatment strategies based on the magneto-mechanochemical effects of MNPs on tumor cells.

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pH-Responsive DNA Origami Switch for Targeted Apoptosis in Tumor Microenvironment

Targeting death receptors (DRs) for cancer therapy holds promise due to their ability to trigger apoptosis in malignant cells. However, the broad expression of DRs in both cancerous and normal tissues has hindered clinical success, primarily due to systemic toxicity. To overcome this limitation, we engineered a DNA origami-based nanorobot that performs conditional, tumor-specific activation of DRs through autonomous structural switching in response to the acidic tumor microenvironment. The nanodevice is constructed with a programmable triplex DNA lock that remains stable at physiological pH (7.4), keeping six TRAIL-mimicking peptide ligands concealed within a closed nanocavity. Under acidic conditions (pH ~6.5), characteristic of solid tumors, the triplex lock dissociates, inducing an open conformation that presents the ligands in a precise 10-nm hexagonal pattern—an arrangement previously shown to be optimal for DR clustering and activation.

We demonstrate that this pH-triggered conformational change results in a potent induction of apoptosis in breast cancer cells in vitro. In vivo, intratumoral administration of the nanorobot in a xenograft mouse model significantly reduced tumor burden—achieving up to 70% tumor growth inhibition—while sparing healthy tissue and avoiding off-target effects. This system exemplifies a new class of “smart” nanomedicines that integrate environmental sensing with spatially organized ligand presentation to execute therapeutic functions with high precision. Our work provides a proof of concept for logic-gated, stimuli-responsive DNA nanorobots with potential applications in targeted cancer therapy and precision medicine.

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Preparation and characterization of poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) P(3HB-co-3HV-co-3HHх)-based nanoparticles for antibacterial drug delivery

Drug delivery systems in the form of biodegradable nanoparticles are becoming increasingly important in medicine. Among the representatives of the polyhydroxyalkanoate family, the most promising for use in biomedicine are copolymers of 3-hydroxybutyric acid with inclusions of 4 HB, 3HV or 3HHx monomers. In this regard, the aim of this work was to obtain a three-component copolymer P(3HB-co-3HV-co-3HHx) using Cupriavidus necator B-10646 and to design nanoparticles on its basis, including those loaded with the antibacterial drug ceftazidime.

P(3HB-co-3HV-co-3HHx) samples were synthesized by Cupriavidus necator B-10646 using oleic acid as a carbon substrate. P(3HB-co-3HV-co-3HHх) carriers were obtained via the emulsification method, loaded with ceftazidime and then characterized in terms of particle morphology and size, drug encapsulation and release. The safety and therapeutic efficacy of nanoparticles were assessed in NIH 3T3, E. coli and St. aureus cell cultures.

Using the emulsification method by changing the experimental conditions, nanoparticles with an average diameter from 450 to 900 nm and a zeta potential of -15 -21 mV were obtained. The sustained release of the drug was demonstrated over 28 days in PBS. The kinetics of ceftazidime release from P(3HB-co-3HV-co-3HHx) nanoparticles is described by the Higuchi and Korsmeyer–Peppas models, which corresponds to the diffusion mechanism. The developed polymer nanoparticles loaded with ceftazidime have antibacterial activity and suppress the development of St. aureus and E. coli, without negatively affecting the adhesion and proliferation of fibroblast cells. The number of viable NIH 3T3 fibroblasts cultured in the presence of P(3HB-3HV-3HHx) nanoparticles is comparable to the control.

The developed P(3HB-3HV-3HHx) nanoparticles can be recommended as promising carriers for the delivery of antibacterial drugs.

This study was funded by State Assignment of the Ministry of Science and Higher Education of the RF (Project No. FWES-2021-0025).

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Polymeric nanomicelles encapsulating aggregation-induced emission (AIE) natural molecules

Introduction

Nanotechnology can provide innovative solutions for the encapsulation of anticancer hydrophobic drugs. Aggregation-induced emission molecules are a newly discovered class of substances that present an enhancement in their emission upon aggregation. Polymeric micelles encapsulating molecules that have both AIE and anticancer properties can be utilized for applications in nanomedicine, such as image-guided drug delivery and surgery.

Methods

In this research, three different amphiphilic random copolymers of poly(oligoethylene glycol methylether methacrylate-co-methyl methacrylate), P(OEGMA-co-MMA) were used for the formulation of nanomicelles encapsulating curcumin and quercetin in different concentrations. Nanosystems’ physicochemical and photophysical properties were studied via Electrophoretic Light Scattering (ELS), Dynamic Light Scattering (DLS), Fluorescence (FS), and UV–Vis Absorption Spectroscopy (UV–Vis).

Results

DLS experiments revealed the formulation of loaded nanomicelles with hydrodynamic radii below 113 nm for curcumin and 241 nm for quercetin. UV-Vis spectroscopy confirmed the encapsulation of curcumin and quercetin inside the nanocarriers. Curcumin was loaded in nanomicelles at a concentration of 10 wt%, while 5 wt% was achieved for quercetin. Fluorescence experiments proved the presence of the AIE phenomenon for both molecules. FBS assay results revealed no interaction between the nanomicelles and serum proteins. Nanoparticles remained stable for 21 days.

Conclusions

A successful formulation of curcumin and quercetin nanocarriers presenting the AIE phenomenon is reported. As FBS assay experiments revealed promising results, further biocompatibility tests can be carried out in order to utilize such formulations in nanomedicine.

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Magnetic Element Doping of Iron Oxide Nanoparticles for Enhanced Performance in Cancer Thermo-Radiotherapy

Thermotherapy in the form of hyperthermia (42-50°C) is often added to cancer treatments to increase the tumor’s sensitivity to adjuvant (chemo)radiotherapy. Magnetic nanoparticles (MNPs) are promising tools for such applications, as they have the capacity to generate heat upon exposure to an alternating magnetic field and simultaneously deliver a radiotherapeutic dose. Optimization of this multifunctional performance implies morphological fine-tuning of MNPs, aiming at high magnetization saturation (MS) values and, hence, high specific loss power (SLP), while incorporating a suitable radiotherapeutic isotope.

In this work, we investigated iron oxide NPs doped with two elements: paramagnetic Mn(II) and lanthanide Ho(III) with a high magnetic moment, prepared by thermal decomposition and co-precipitation, respectively, resulting in MS values that increased by up to 1.7 times and improved heating efficiency at 346 kHz and 23 mT. In addition, a pronounced Mn(II) outer rim obtained for higher Mn(II)-content NPs allowed the detection of T1-weighted MRI contrast convenient for monitoring NPs distribution in tissues due to the water exchange at the NPs' surface. The SLP values of NPs doped with Ho(III) into the Fe-oxide lattice were demonstrated to be dependent on both size and Ho content, with the best-performing NPs being 12 nm with 2.5% Ho. Furthermore, the presence of Ho(III) within the Fe-oxide lattice, in addition to higher SLP, offers the opportunity to perform radiotherapy using the 166Ho-isotope, a b-emitter (t1/2=27h) produced by the stable 165Ho via neutron activation.

These findings demonstrate that Fe-oxide NPs containing magnetic elements with additional functionalities provide the basis for the further development of hybrid materials with enhanced thermotherapeutic performance in combination with radiotherapy.

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Research on Improving the Efficiency of aquaculture Using Self-Powered Triboelectric Nanogenerators and Microfluidic Technology

Aquaculture, a vital sector within the marine economy, is increasingly focused on improving breeding efficiency to support sustainable industrial growth. However, deep-sea aquaculture faces several challenges, including high operational costs, complex environmental control systems, and specific issues such as water pollution, hypoxia, and low feeding efficiency in fish. To overcome these barriers, emerging nanotechnologies like Triboelectric Nanogenerator (TENG) technology and microfluidic technology offer innovative solutions. TENG technology, by harnessing mechanical energy from ocean waves, can provide a sustainable power supply for aquaculture systems, reducing the dependency on traditional, expensive energy sources. This energy can be used to power equipment, sensors, and other vital systems within the aquaculture environment, making the operation more cost-effective and environmentally friendly. On the other hand, microfluidic technology optimizes water quality and enhances feed distribution by precisely controlling the flow of fluids in aquaculture systems. This capability helps maintain a stable environment, crucial for the health and growth of marine organisms. Moreover, both TENG and microfluidic devices can function as efficient sensors, enabling real-time monitoring of biological behavior, environmental conditions, and other key parameters. By integrating these technologies into marine cage aquaculture, the industry can achieve better environmental control, reduced energy costs, and improved breeding outcomes, supporting the long-term sustainability and profitability of the sector.

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Formulation and Therapeutic Evaluation of Beta vulgaris-Mediated Zinc Nanoparticles for the Management of Inflammatory Disorders

Abstract (200–300 words):

The increasing demand for sustainable, biocompatible nanotherapeutics has drawn attention to green synthesis methods using plant-based resources. Beta vulgaris (beetroot), known for its rich polyphenolic and antioxidant content, presents great potential as a natural reducing and stabilizing agent in nanoparticle production. This study explores the green synthesis, characterization, and anti-inflammatory evaluation of zinc nanoparticles (ZnNPs) mediated by Beta vulgaris extract.

ZnNPs were synthesized using aqueous root extracts of Beta vulgaris via a bottom-up approach. The phytochemicals in the extract facilitated an efficient reduction in zinc ions and stabilization of the nanoparticles. Reaction parameters such as pH, temperature, and extract concentration were optimized to ensure reproducibility and product quality. The resulting colloidal suspension remained stable without visible aggregation for several weeks.

Comprehensive characterization was carried out using UV-Vis spectroscopy, FTIR and SEM. SEM analysis showed an average particle size of 68 ± 5 nm with a polydispersity index (PDI) of <0.3, indicating excellent homogeneity. SEM images confirmed spherical morphology with particle sizes ranging from 50 to 80 nm. FTIR spectra confirmed no drug-excipient incompatibility in nanoparticle stabilization.

Anti-inflammatory activity was evaluated using protein denaturation and nitric oxide scavenging assays, revealing potent effects comparable to standard drugs. The observed activity may be due to the synergistic antioxidant effects of Beta vulgaris and the immunomodulatory properties of zinc, potentially through NF-κB pathway inhibition.

This study highlights a green, cost-effective route for synthesizing stable and bioactive ZnNPs with promising pharmaceutical applications for managing inflammatory disorders.

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