Search Results (210)

Background/Objectives: Oleosomes, plant-derived lipid nanostructures comprising a triacylglycerol core surrounded by a phospholipid monolayer and interfacial proteins, provide sustainable alternatives to synthetic lipid vesicles. This study compares solvent-free aqueous extractions of oleosomes from five nuts (almond, macadamia, walnut, hazelnut, pine) and five seeds (flaxseed, sunflower, hemp, sesame, canola/rapeseed) to understand how botanical origin influences composition and physicochemical behavior. Methods: Oleosomes were isolated using solvent-free aqueous extraction. Extraction yield, lipid content, protein content, particle size, polydispersity, and zeta potential were determined using standard analytical assays and dynamic light scattering techniques. SDS–PAGE was performed to evaluate interfacial protein profiles and oleosin abundance. Results: Extraction yields ranged from 8.4% (flaxseed) to 59.5% (walnut). Oleosome diameters spanned 424 nm to 3.9 µm, and all oleosome dispersions exhibited negative zeta potentials (–26 to –57 mV). SDS–PAGE revealed abundant 15–25 kDa oleosins in seed oleosomes but relatively sparse proteins in nut oleosomes. Seed oleosomes were smaller and exhibited stronger electrostatic stabilization, while nut oleosomes formed larger droplets stabilized primarily through steric interactions due to lower oleosin content. Conclusions: Variation in oleosin abundance and interfacial composition leads to distinct stabilization mechanisms in nut and seed oleosomes. These findings establish a predictive basis for tailoring oleosome size, stability, and functionality, and highlight their potential as natural nanocarriers for food, cosmetic, and pharmaceutical formulations. Full article

The application of nanotechnology in medicine has garnered significant interest, particularly in the development of advanced drug delivery systems. Graphene oxide (GO) shows promise as a carrier for delivering microRNA (miRNA) mimics or antisense constructs. miRNAs play a crucial role in regulating gene expression, and their dysregulation is associated with various diseases, including cancer. This study aimed to evaluate the impact of graphene oxide on cellular signaling pathways and its potential as a platform for gene delivery by developing a GO–antisense miRNA-21 nanosystem in HepG2 liver cancer cells. A colloidal dispersion of GO was used to prepare GO-antisense miRNA-21 nanosystems via self-assembly. The nanosystem was characterized in terms of ultrastructure, size distribution, surface composition and binding by TEM, DLS, ATR-FTIR and UV-Vis spectra. Zeta potential measurements were conducted to evaluate nanosystem stability by assessing the release kinetics of antisense miRNA-21. The efficiency of the GO nanosystem in delivering antisense miRNA-21 into HepG2 cells was analyzed using confocal microscopy and flow cytometry. Given the central role of miRNA-21 in inflammatory and oncogenic pathways, we first assessed its expression following GO exposure. In line with previous studies reporting high miRNA-21 expression in hepatocellular carcinoma cells, GO treatment further increased miRNA-21 levels in HepG2 cells compared with untreated controls. Changes in the expression levels of IL-8, MCP-1, ICAM-1, TIMP-2, and NF-kB were quantified by qPCR analysis. The ultrastructural analysis confirmed a strong affinity between GO and antisense miRNA-21. Transfection results demonstrate that the GO-based nanosystem effectively delivered antisense miRNA-21 into HepG2 cells, leading to a reduction in the expression of key pro-inflammatory genes. These findings suggest that GO-based nanocarriers may offer a promising strategy for delivering localized intratumoral miRNA-based therapies that target gene regulation in hepatocellular carcinoma. Full article

Fatty acid vesicles (FAVs) are promising nanocarriers, but their application is limited by a narrow, alkaline pH formation window that mismatches the weak acidity of physiological environments, such as skin. To overcome this, we developed composite vesicles using oleic acid (OA) and the non-ionic surfactant Tween 40 (TW40). pH titration confirmed that the OA/TW40 system successfully broadened the vesicle formation window from 8.2–10.08 to 3.1–7.2, aligning it with the physiological pH range. The bioactive flavonoid luteolin (LUT) was efficiently encapsulated into these OA/TW40-FAVs, achieving a high encapsulation efficiency (EE) of 87.13% and a drug loading capacity (DLC) of 9.58. The formulation demonstrated superior topical delivery performance: the cumulative transdermal flux (933.08 µg·cm⁻²) and skin retention (68.18 µg·cm⁻²) were both approximately double that of the free LUT solution. Furthermore, the OA/TW40/LUT-FAVs provided sustained drug release and exhibited synergistically enhanced antioxidant and antimicrobial activities compared to free LUT or blank vesicles. Collectively, these findings establish OA/TW40 composite vesicles as a robust and efficient nanoplatform for the topical delivery of bioactive compounds. Full article

Melanoma is one of the most aggressive skin cancers and requires innovative therapeutic strategies to overcome the limitations of conventional therapies. In this work, upconversion nanoparticles coated with mesoporous silica and functionalized with folic acid (UCNP@mSiO₂-FA) were developed as a targeted nanocarrier system for the delivery of doxorubicin (DOX). The UCNPs were synthesized via thermal decomposition, coated with mesoporous silica shells, and functionalized with folic acid (FA) to enable receptor-mediated targeting. DOX was then loaded into the mesoporous silica coating by adsorption, yielding UCNP@mSiO₂-FA-DOX. The different UCNPs were characterized for size, composition, colloidal stability, and loading and release of DOX. This comprehensive physicochemical characterization confirmed a high DOX loading efficiency and a slightly increased drug release under acidic conditions, mimicking the tumour microenvironment. In vitro assays using four melanoma cell lines (A375, B16-F10, MNT-1, and SK-MEL-28) revealed an excellent biocompatibility of UCNP@mSiO₂-FA and a significantly higher cytotoxicity of UCNP@mSiO₂-FA-DOX compared to unloaded UCNPs, in a dose-dependent manner. Cell cycle analysis demonstrated G2/M phase arrest after treatment with UCNP@mSiO₂-FA-DOX, confirming its antiproliferative effect. Overall, UCNP@mSiO₂-FA-DOX represents a promising nanoplatform for targeted melanoma therapy, combining active tumour targeting and enhanced anticancer efficacy. Full article

Liposomes started to be studied for drug delivery in 1970s, taking advantage of their ability to encapsulate hydrophilic and hydrophobic drugs using biodegradable and biocompatible molecules. Nowadays, they remain one of the most promising strategies for drug delivery not only in cancer treatment but also in gene therapies and vaccines. The design and development of liposomal systems have evolved significantly over the past decades, moving from conventional formulations to advanced, stimulus-responsive, and multifunctional nanocarriers. Analogous to the myth of the Trojan Horse, liposomes must mislead the host immune system to reach the interior of cancer cells in order to deliver the therapeutic payload. There are many barriers that liposomes have to overcome to circulate through the bloodstream and specifically target cancer cells without damaging other tissues. Crucial parameters such as lipid composition, particle size, zeta potential, and PEGylation have been systematically optimized to enhance pharmacokinetics and biodistribution and to improve delivery efficiency. Furthermore, conjugation with antibodies, peptides, or small molecules has enabled active targeting, while stimuli such as pH, temperature, and enzymatic activity have been exploited for controlled drug release within the tumor microenvironment. Such innovations have laid the groundwork for translating liposomal formulations from the bench to clinical applications. In this paper, we evaluate the physicochemical features of liposomal design that underpin their suitability and efficacy for anticancer drug delivery. We aimed to focus on two main aspects: conducting an exhaustive review of the physicochemical parameters of liposomal drugs that have already been approved by regulatory agencies, while maintaining a pedagogical approach when explaining the key design parameters for the optimal design of liposomes in oncology in detail. Full article

Polymeric micelles are widely studied as nanocarriers for hydrophobic drugs, yet their structural stability under physiological conditions remains a major limitation. This review provides a comparative evaluation of synthetic and natural polymeric micelles with a focus on their stability under dilution and in protein-rich environments. The discussion integrates thermodynamic and kinetic factors governing micelle integrity and examines how molecular composition, hydrophobic segment length, and core–shell modifications influence disintegration behavior. While synthetic micelles commonly collapse below their critical micelle concentration during intravenous administration, natural polymeric micelles, such as those derived from chitosan, alginate, or heparin, exhibit improved resistance to dilution but remain vulnerable to protein-induced destabilization. Strategies such as core or shell cross-linking, surface functionalization, and natural polymer coatings are reviewed as promising approaches to enhance circulation stability and controlled drug release. The work provides a framework for designing micellar systems with balanced biocompatibility, biodegradability, and robustness suitable for clinical drug-delivery applications. Full article

Background: Mesoporous silica nanoparticles (MS NPs) have attracted significant interest for their role in the advancement of drug delivery systems. However, further investigation is needed to unravel the mechanisms behind the shift in organ tropism that occurs with changes in composition. Methods: To shed light on the correlation between their composition and organ-targeting capabilities, a range of MS NPs was synthesized and subsequently administered intravenously to mice. Results: Our results indicate that MS NPs with a pristine -Si-O-Si- framework, or those incorporating -C-C- or –S-S-S-S- bonds, predominantly accumulated in the liver. The shift to lung tropism was observed exclusively in MS NPs that were enriched with –SH groups. Proteomic analysis identified histidine-rich glycoprotein (HRG) as the most prevalent protein associated with liver-preferred MS NPs in serum, while lung-preferred MS NPs, such as thioether-bridged deformable hollow mesoporous organosilica nanoparticles (HSMONs), showed the highest affinity for albumin. Furthermore, the lung-selective HSMONs, endowed with inherent deformability and glutathione-responsive biodegradability, were utilized as systemic nanocarriers for the delivery of gambogic acid (GA). Conclusions: Leveraging albumin absorbing-triggered tumor cell targeting and trafficking, HSMONs conjugated with GA effectively elicited potent antitumor effects in pulmonary tissue. Full article

Food spoilage and contamination remain pressing global challenges, undermining food security and safety while driving economic losses. Conventional preservation strategies, including thermal treatments, refrigeration, and synthetic additives, often compromise nutritional quality and raise sustainability concerns, thereby necessitating natural, effective alternatives. Curcumin, a polyphenolic compound derived from Curcuma longa, has demonstrated broad-spectrum antimicrobial, antioxidant, and anti-inflammatory activities, making it a promising candidate for food preservation. However, its poor solubility, instability, and low bioavailability limit direct applications in food systems. Advances in nanotechnology have enabled the development of nanoformulated curcumin, enhancing solubility, stability, controlled release, and functional efficacy. This review examines the antimicrobial mechanisms of curcumin and its nanoformulations, including membrane disruption, oxidative stress via reactive oxygen species, quorum sensing inhibition, and biofilm suppression. Applications in active and smart packaging are highlighted, where curcumin nanoformulation not only extends shelf life but also enables freshness monitoring through pH-responsive color changes. Evidence across meats, seafood, fruits, dairy, and beverages shows improved microbial safety, oxidative stability, and sensory quality. Multifunctional systems, such as hybrid composites and stimuli-responsive carriers, represent next-generation tools for sustainable packaging. However, challenges remain with scale-up, migration safety, cytotoxicity, and potential promotion of antimicrobial resistance gene (ARG) transfer. Future research should focus on safety validation, advanced nanocarriers, ARG-aware strategies, and regulatory frameworks. Overall, nanoformulated curcumin offers a natural, versatile, and eco-friendly approach to food preservation that aligns with clean-label consumer demand. Full article

The plasma membrane (PM) of eukaryotic cells plays a key role in the response to stress, acting as the first line of defense against environmental changes and protecting cells against intracellular perturbations. In this work, we explore how membrane-bound chaperones and membrane lipid domains work together to shape plasma membrane properties—a partnership we refer to as the “epichaperome–plasma membrane lipid axis.” This axis influences membrane fluidity, curvature, and domain organization, which in turn shapes the spatial and temporal modulation of signaling platforms and pathways essential for maintaining cellular integrity and homeostasis. Changes in PM fluidity can modulate the activity of ion channels, such as transient receptor potential (TRP) channels. These changes also affect processes such as endocytosis and mechanical signal transduction. The PM proteome undergoes rapid changes in response to membrane perturbations. Among these changes, the expression of heat shock proteins (HSPs) and their accumulation at the PM are essential mediators in regulating the physical state and functional properties of the membrane. Because of the pivotal role in stress adaptation, HSPs influence a wide range of cellular processes, which we grouped into three main categories: (i) mechanistic insights, differentiating in vitro (liposome, reconstituted membrane systems) and in vivo evidence for HSP-PM recruitment; (ii) functional outputs, spanning how ion channels are affected, changes in membrane fluidity, transcytosis, and the process of endocytosis and exosome release; and (iii) pathological effects, focusing on how rewired lipid–chaperone crosstalk in cancer drives resistance to drugs through altered membrane composition and signaling. Finally, we highlight Membrane Lipid Therapy (MLT) strategies, such as nanocarriers targeting specific PM compartments or small molecules that inhibit HSP recruitment, as promising approaches to modulate the functional stability of epichaperome assembly and membrane functionality, with profound implications for tumorigenesis. Full article

This study focuses on the preparation of poly(HCQM-co-VP) copolymeric nanoparticles (NPs) to enhance the aqueous solubility and bioavailability of the hydrophobic and antitumor molecules HCQ (hydroxychloroquine) and α-TOS (α-tocopheryl succinate). HCQ is covalently incorporated into the polymer backbone, while α-TOS is encapsulated within the nanoparticles by non-covalent interactions. Poly(HCQM-co-VP) was synthesized from a vinyl derivative of HCQ (HCQM) and N-vinylpyrrolidone (VP), with a molar composition of 17% HCQM and 83% VP, providing the optimal hydrophobic/hydrophilic balance for forming, via nanoprecipitation, empty nanoparticles (NPs) with a diameter of 123.6 nm and a zeta potential of −5.8 mV. These nanoparticles effectively encapsulated α-TOS within their hydrophobic core, achieving an encapsulation efficiency (%EE) of 78%. These α-TOS-loaded NPs resulted in smaller diameters and more negative zeta potentials (71 nm, −19.2 mV) compared to the non-loaded NPs. The cytotoxicity of these NPs was evaluated using the AlamarBlue assay on MCF-7 breast cancer cells. The empty NPs showed no toxic effects within the tested concentration range, after 72 h of treatment. In contrast, the α-TOS-loaded NPs, exhibited a pronounced cytotoxic effect on MCF-7 cells with an IC₅₀ value of 100.2 μg·mL⁻¹, thereby demonstrating their potential as controlled drug delivery systems for cancer treatment. These findings contribute to the development of a new HCQ-based polymeric nanocarrier for α-TOS or other hydrophobic drugs for the treatment of cancer and other diseases treatable with these drugs. Full article

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia and associated complications such as cardiovascular disease, nephropathy, retinopathy, neuropathy, and chronic non-healing wounds. Current antidiabetic therapies offer only partial glycemic control and are limited by poor bioavailability, adverse effects, and an inability to prevent disease progression. Plant-derived exosome-like nanoparticles (PENPs) have emerged as a promising class of natural nanocarriers with excellent biocompatibility, low immunogenicity, and intrinsic multi-component bioactivity. However, few reviews have addressed recent progress in PENPs for DM therapy. To capture the recent developments in this area, this review provides a systematic synthesis of recent advances in PENPs for DM therapy, covering plant sources, extraction and purification methods, molecular compositions, and therapeutic mechanisms. Preclinical studies have demonstrated that PENPs can improve hyperglycemia, enhance insulin sensitivity, regulate hepatic lipid metabolism, and promote wound healing by modulating oxidative stress, inflammation, gut microbiota, glucose metabolism, and insulin signaling. Additionally, PENPs have been shown to promote angiogenesis via glycolytic reprogramming. Despite these promising findings, challenges including scalable isolation, standardized physicochemical characterization, and clinical translation remain. Future directions include engineering multifunctional PENPs, establishing Good Manufacturing Practice (GMP)-compliant production, and conducting clinical trials to facilitate their integration into precision therapeutics for diabetes management. Full article

Background/Objectives: Biodegradable and pH-responsive nanocarriers using zwitterionic moieties represent a promising avenue for targeted delivery of chemotherapeutics. The present study addresses this by developing zwitterionic nanoparticles based on polylactic acid/poly(ethylene adipate) (PLA/PEAd) copolymers grafted with SBMA, designed to combine acid-triggered drug release with stealth-like biocompatibility. Methods: A series of polylactic acid/poly(ethylene adipate) (PLA/PEAd) copolymers with varying compositions (95/5, 90/10, and 75/25 w/w) were synthesized via ring-opening polymerization, followed by controlled radical grafting of the zwitterionic monomer [2-(Methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), which was then successfully grafted upon their backbone. The resulting zwittenionic copolymers were thoroughly characterized for their structural and physicochemical properties, displaying tunable molecular weights of 3200–4900 g/mol, enhanced hydrophilicity and controlled degradation, with mass loss ranging from 8% to 83% over 30 days, depending on PEAd content and pH. Paclitaxel-loaded nanoparticles of spherical shape with sizes ranging from 220 to 565 nm were then fabricated. Drug release was pH-dependent with significantly higher release at pH 5.0 (up to ~79% for PLAPEAd7525-SBMA) compared to pH 7.4 (~18–35%). Hemolysis assays demonstrated excellent hemocompatibility, and cytotoxicity studies showed strong anticancer activity (>80% cell death in MDA-MB-231) with lower toxicity toward iMEFs, especially for PEAd-rich formulations. Conclusions: Our findings underline the potential of SBMA-functionalized PLA/PEAd nanoparticles as effective nano-carriers for tumor-targeted chemotherapy. Full article

Nano-based drug delivery systems present a promising approach to improve the efficacy and safety of therapeutics by enabling targeted drug transport and controlled release. In parallel, computational approaches—particularly Molecular Dynamics (MD) simulations and Artificial Intelligence (AI)—have emerged as transformative tools to accelerate nanocarrier design and optimise their properties. MD simulations provide atomic-to-mesoscale insights into nanoparticle interactions with biological membranes, elucidating how factors such as surface charge density, ligand functionalisation and nanoparticle size affect cellular uptake and stability. Complementing MD simulations, AI-driven models accelerate the discovery of lipid-based nanoparticle formulations by analysing vast chemical datasets and predicting optimal structures for gene delivery and vaccine development. By harnessing these computational approaches, researchers can rapidly refine nanoparticle composition to improve biocompatibility, reduce toxicity and achieve more precise drug targeting. This review synthesises key advances in MD simulations and AI for two leading nanoparticle platforms (gold and lipid nanoparticles) and highlights their role in enhancing therapeutic performance. We evaluate how in silico models guide experimental validation, inform rational design strategies and ultimately streamline the transition from bench to bedside. Finally, we address key challenges such as data scarcity and complex in vivo dynamics and propose future directions for integrating computational insights into next generation nanodelivery systems. Full article

Background/Objectives: The conventional treatment of glioblastoma (GBM) with alkylating agents is not curative. The protein O6-methylguanine DNA methyltransferase (MGMT) is a significant limitation, being able to repair drug-induced DNA damage. Thus, exploring non-alkylating agents already approved by the FDA is imperative. The antidepressant fluoxetine (FL) has been explored due to its anti-cancer properties. However, its first-pass effect and its non-targeted distribution to brain tissue are major limitations of FL’s administration, which is conventionally orally administered. Thus, the primary objective of this work was the development of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) tailored with folic acid (FA) for FL delivery to GBM cells. Methods: A Central Composite Design (CCD) was applied to optimize the NPs. Results: The developed FA-functionalized PLGA NPs exhibited physicochemical properties suitable for brain-targeted delivery. The final formulation presented an average diameter of 167 ± 8 nm, a polydispersity index (PdI) of 0.23 ± 0.07, and a zeta potential of −22.2 ± 0.3 mV. The encapsulation efficiency (EE) and loading capacity (LC) values were 44.4 ± 3.8% and 3.1 ± 0.3%, respectively. In vitro studies demonstrated that the NPs are stable in storage and simulated physiological conditions and can maintain a controlled and slow-release profile of FL for 17 days. In vitro cell uptake experiments demonstrated that conjugation with FA enhances the NPs’ internalization in GBM cells overexpressing folate receptors through endocytosis mediated by this receptor. Furthermore, in vitro cytotoxicity experiments demonstrated that the FL encapsulation in the developed NPs maintains drug efficacy, as well as it was able to increase cell sensitivity to treatment with an alkylating agent. Conclusions: These results suggest that the developed NPs are effective nanocarriers, either as a standalone therapy or as a chemosensitizer in combination with the standard GBM treatment. Full article

The use of nanoparticles has revolutionized drug delivery by enabling targeted and controlled therapeutic release. However, their interactions with intracellular organelles, particularly lysosomes, are not yet fully understood. This study delineates the differential effects of two widely used nanocarriers—mesoporous silica (MSNs) and albumin (ANPs) nanoparticles—on lysosomal biology, with a focus on the expression and activity of cathepsins (CtsB and CtsD), which are key proteases involved in protein degradation and maintaining cellular balance. These two types of nanoparticles, differing in their material and degradability, exhibit distinct behaviors inside the cell. We demonstrate that inorganic MSNs cause significant changes in lysosomal function by altering lysosomal content and cathepsin levels, without triggering lysosomal membrane permeabilization—a typical response to organic particle stress. In contrast, ANPs—which are susceptible to lysosomal cathepsin degradation—induce milder changes in cathepsin expression and maintain lysosomal integrity. Our results highlight that the composition of nanocarriers plays a pivotal role in modulating lysosomal protease activity and maintaining overall cellular homeostasis, highlighting the importance of these parameters in the rational design of drug delivery platforms. Full article