Search Results (34)

Ovarian cancer is the most lethal gynecologic malignancy, with chemoresistance and recurrence driven by cancer stem cells (CSCs). Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) mediate tumor–stroma communication, but their role in ovarian cancer progression and therapy remains unclear. Here, we investigated bone marrow (BM)-MSC-EVs, their effects on ovarian cancer cells, and the underlying molecular mechanisms. BM-MSCs were isolated, confirmed using flow cytometry and trilineage differentiation, and their EVs characterized using nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. Kuramochi cells were treated with BM-MSC-EVs and assessed for proliferation, colony formation, migration, invasion, apoptosis, and chemosensitivity. Aldehyde dehydrogenase (ALDH⁺) Kuramochi cells, with or without EV exposure, were transplanted into non-obese diabetic severe combined immunodeficiency mice for xenograft studies, followed by histology, immunohistochemistry, Western blotting, and EV miRNA profiling. BM-MSC-EVs increased cancer cell proliferation but reduced colony formation, migration, and invasion in vitro. They sensitized ALDH⁺ CSC-like cells to carboplatin, while paclitaxel response remained unchanged. In vivo, EVs accelerated tumor growth and activated prosurvival (p-AKT, BCL-2), angiogenic (VEGFA, CD31), and epithelial–mesenchymal transition-associated (vimentin) pathways. EVs were found to be enriched in hsa-miR-100-5p, hsa-miR-122-5p, and hsa-let-7i-5p based on miRNA array analysis, and these findings were further validated by qRT-PCR. These findings reveal the dual roles of BM-MSC-EVs: enhancing carboplatin sensitivity while promoting tumor progression and angiogenesis. Full article

Modern medicine requires effective, continuous, and safe therapies, which largely depend on the targeted delivery and activity of the drug. This goal can be achieved by designing drug delivery systems with improved pharmacokinetic properties and enhanced drug transport to the affected tissue. Human serum albumin (HSA) is an attractive carrier for the synthesis of therapeutic nanoparticles, several of which have already been approved by the United States Food and Drug Administration (FDA). The success of Abraxane as an effective treatment for metastatic breast cancer and non-small cell lung carcinoma, the application of Optison in ultrasound imaging, and the use of Nanocoll as an agent for SPECT diagnostics in sentinel node localisation confirm the strong potential of albumin-based systems. Further benefits are expected in patients with soft tissue cancers, as LadRx is seeking FDA marketing approval for Aldoxorubicin. The future of oncology lies in theranostics, which combines a tumour-localising factor on one platform with a drug targeting cancer cells and a factor that activates the cytotoxicity of the drug after it reaches the target tissue. This article presents recent advancements in albumin-based nanoparticles for drug delivery, targeting, and imaging. It also briefly discusses methods of synthesis and surface modification of albumin nanocarriers to enable targeted delivery to pathological sites. Finally, it outlines the latest approaches in multimodal theranostic platforms, highlighting albumin’s potential to improve cancer therapy. Full article

This study reports the development of paclitaxel (PTX)-loaded human serum albumin (HSA) nanoparticles (NPs), surface-decorated with trastuzumab (TMAB), with potential applicability in HER2-oriented delivery. The NPs were obtained via thermally driven self-assembly followed by non-covalent antibody adsorption and they were characterized using Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and ζ-potential analysis. The drug association efficiency (%DAE), defined exclusively for PTX, was high for both HSA-PTX and HSA-PTX-TMAB NPs (96.4% and 98.2% w/w, respectively), with loading capacities (%LC) of 8.9% and 7.4%, respectively. TMAB decoration led to a modest increase in mean diameter and a reduction in surface charge, consistent with successful surface modification. Both formulations exhibited rapid early-phase PTX release followed by an apparent stabilization phase, with distinct kinetic behavior between HSA–PTX and HSA–PTX–TMAB NPs. Cytotoxicity in A549 cells after 18 h of exposure showed modest, non-differential effects consistent with controlled release and short-term assessment of non-specific toxicity. Overall, this thermally assembled albumin-based system provides a promising foundation for further evaluation of HER2-oriented PTX delivery. Full article

Human serum albumin (HSA), an endogenous protein, was employed in the synthesis of nanoparticles. The treatment of an HSA solution with ethanol and glutaraldehyde resulted in the formation of human serum albumin nanoparticles (HSA NPs), which exhibited a weak fluorescence emission peak at 515 nm upon excitation at 360 nm. Importantly, these synthesized HSA NPs displayed a pronounced fluorescence polarization (FP) signal under identical excitation and emission conditions. Furthermore, incubation of the HSA NPs with specific DNA aptamers targeting lysozyme and thrombin led to a significant decrease in the FP values. This reduction in FP was effectively reversed upon the addition of lysozyme and thrombin. Based on these observations, a label-free fluorescence polarization-based detection platform for lysozyme and thrombin was developed utilizing HSA NPs and a DNA aptamer system. Full article

Treating brain cancer remains challenging due to the blood–brain barrier (BBB) and the systemic toxicity of chemotherapy. This study focuses on developing human serum albumin (HSA) nanoparticles modified with low-molecular-weight protamine (LMWP) to improve crossing the BBB and enable targeted delivery of curcumin and temozolomide (TMZ). Nanoparticle stability was enhanced by crosslinking with aldehyde groups from oxidized gellan (OG). The successful attachment of LMWP to HSA at the thiol group of Cys34 was confirmed through FT-IR and ¹H-NMR analyses. Most self-assembled nanoparticles were smaller than 200 nm in diameter. Curcumin showed higher encapsulation efficiency than TMZ. In vitro drug release was pH-dependent: curcumin released more at pH 7.4, while TMZ release was better at pH 4. Higher crosslinking degrees reduced drug release. Cytotoxicity assays on V79-4 (normal) and C6 (glioma) cell lines showed increased apoptosis and significantly lower IC₅₀ values for co-encapsulated formulations, indicating a synergistic effect. Curcumin’s antioxidant activity was maintained and protected from UV degradation by the polymer matrix. The parallel artificial membrane permeability assay (PAMPA) confirmed that the functionalized formulations with co-encapsulated drugs could cross the BBB. Hemocompatibility studies indicated a favorable profile for intravenous use. Full article

We report the synthesis and characterization of folic acid (FA)-conjugated human serum albumin nanoparticles, (HSA-FA):Ru NPs, as targeted carriers for rutin (Ru), a flavonoid with known anticancer activity. Nanoparticles were fabricated via a desolvation method, and their surface was functionalized with folic acid to promote selective uptake by cancer cells overexpressing folate receptors. Morphological and dimensional analyses performed by atomic force microscopy (AFM), scanning electron microscopy (SEM), and fluorescence microscopy confirmed that all nanoparticles were below 100 nm and exhibited good colloidal stability. Voltametric measurements confirmed the successful incorporation of both rutin and folic acid within the (HSA-FA):Ru nanoparticle formulation. Biological evaluation was conducted on healthy L929 fibroblasts and HT-29 colon adenocarcinoma cells. MTS colorimetric assays revealed that (HSA-FA):Ru NPs significantly reduced the viability of HT-29 cells, while maintaining higher compatibility with L929 cells. Fluorescence and electron microscopy further confirmed preferential nanoparticle uptake and surface accumulation in HT-29 cells, supporting the role of folic acid in enhancing targeted delivery. The study demonstrates that HSA-based nanoparticles functionalized with FA and loaded with Ru offer a biocompatible and efficient strategy for selective intracellular drug delivery in colorectal cancer. These findings support the use of albumin-based nanocarriers in the development of targeted therapeutic platforms for cancer treatment. Full article

Human serum albumin (HSA) plays a fundamental role in the human body, including the transport of exogenous and endogenous substances. HSA is also a biopolymer with a great medical and pharmaceutical potential. Due to nontoxicity and biocompatibility, this protein can be used as a nanocarrier. 10-(2′-Pyrimidyl)-3,6-diazaphenothiazine (10-Pyr-3,6-DAPT) is a phenothiazine showing high anticancer potential in vitro against glioma, melanoma and breast cancer cells. Additionally, this compound is characterized by selectivity of action towards MCF-7 breast cancer and has low cytotoxicity towards normal cells. Considering the promising pharmacological potential of this compound and using spectroscopic techniques, HSA and human serum albumin nanoparticles (HSA-NP) were tested as carriers of this molecule. Based on the obtained data and the appropriate mathematical models (Stern-Volmer and Klotz models), it can be concluded that 10-Pyr-3,6-DAPT probably forms a weak (K_a = (5.24 ± 0.57) $\times$ 10⁴ and K_a = (4.67 ± 0.59) $\times$ 10⁴) for excitation wavelengths λ_ex 275 nm and λ_ex 295 nm, respectively) static complex (k_q > 10¹⁰) with HSA (at Sudlow site II (subdomain IIIA), and the phenomenon of it having both strong therapeutic and toxic effects is possible. High encapsulation efficiency of 10-Pyr-3,6-DAPT into the HSA-NPs was obtained, and the changes in albumin secondary structure due to the presence of 10-Pyr-3,6-DAPT were registered. Based on the data presented, it can be concluded that due to the high toxic effects of 10-Pyr-3,6-DAPT, a better carrier may be HSA-NPs. Full article

Background/Objectives: The key components of the blood–brain barrier (BBB) are endothelial cells, pericytes, astrocytes, and the capillary basement membrane. The BBB serves as the main barrier for drug delivery to the brain and is the most restrictive endothelial barrier in the body. Nearly all large therapeutic molecules and over 90% of small-molecule drugs cannot cross the BBB. To overcome this challenge, nanotechnology, particularly drug delivery systems such as nanoparticles (NPs), have gained significant attention. Methods: Poly(lactide-co-glycolide) (PLGA) and albumin-based NPs (bovine/human), with or without transferrin (Tf) ligands (BSA, HSA, BSA-Tf, HSA-Tf), and nanolipid carriers (NLC) were synthesized. The interactions of these NPs with human brain microvascular endothelial cells (hBMECs), human brain vascular pericytes (hBVPs), and human astrocytes (hASTROs) were analyzed. Results: At doses of 15.62 µg/mL, 31.25 µg/mL, and 62.5 µg/mL, none of the NPs caused toxic effects on hBMECs, hBVPs, or hASTROs after 3 h of incubation. All NPs were internalized by the cells, but BSA-Tf and HSA-Tf showed significantly higher uptake in hBMECs in a dose-dependent manner. Ultrastructural analysis revealed notable differences between NP formulation and cell type. Conclusions: Our findings underscore the potential of ligand-targeted NPs to selectively interact with BBB endothelial cells. Ultrastructural analysis reveals distinct cellular processing pathways for various NP formulations across BBB-associated cell types, with autophagy emerging as a crucial mechanism for NP handling in pericytes and astrocytes. Changes in NP chemical properties upon biological exposure present significant challenges for nanomedicine design, emphasizing the need for further investigation into NP interactions at the cellular and subcellular levels. Full article

In the present work, we studied the interactions of three types of iron oxide nanoparticles (IONPs) with human serum albumin (HSA) by fluorescence and UV-Vis spectroscopy. The determined binding parameters of the reactions and the thermodynamic parameters, including ΔHo, ΔSo, and ΔGo indicated that electrostatic forces play a major role in the interaction of IONPs with HSA. These measurements indicate a fluorescent quenching mechanism based on IONPs-HSA static complex formation. Our study shows that the interaction between HSA and IONPs depends on the nanoparticle structure. The interaction between IONPs and HSA was found to be spontaneous, exothermic, and entropy-driven. HSA was shown to interact moderately with IONPs obtained with plant extracts of Uncaria tomentosa L. (IONP@UT) and Clinopodium vulgare L. (IONP@CV), and firmly with IONPs prepared with Ganoderma lingzhi (Reishi) extract (IONP@GL), via ground-state association. Analysis by modified Stern-Volmer approximation indicates that the quenching mechanism is static. Our study significantly improves our understanding of the mechanisms of interaction, distribution, and transport involved in the interaction between proteins and IONPs. It provides crucial insights into the functional perturbations of albumin binding capacity and the effects of IONPs on the stability and structural modifications of plasma carrier proteins. Full article

Background: Rheumatoid arthritis (RA) tends to occur in symmetrical joints and is always accompanied by synovial hyperplasia and cartilage damage. Triptolide (TP), an extract from Tripterygium, has anti-inflammatory and immunomodulatory properties and could be used in the treatment of RA. However, its poor water solubility and the multi-system lesions caused by the use of this substance limit its clinical application. Therefore, it would be of great significance to assemble a composite nanoparticle hydrogel and apply it to a collagen-induced arthritis (CIA) mouse model to investigate the therapeutic effect and biosafety of this compound. Method: TP@HSA nanoparticles (TP@HSA NPs) were fabricated with a self-assembly method; a thermosensitive hydrogel loaded with the TP@HSA NPs (TP@HSA NP hydrogel) was prepared by using chitosan and beta- glycerophosphate (β-GP) and was then intra-articularly injected into CIA mice. The changes in joint swelling were measured with a digital caliper, and inflammation and cartilage damage were evaluated by using hematoxylin and eosin (H&E) and safranin O–fast green (SO&FG) staining, respectively. Results: TP@HSA NPs with an average diameter of 112 ± 2 nm were successfully assembled, and their encapsulation efficiency and drug loading efficiency were 47.6 ± 1.5% and 10.6 ± 3.3%, respectively. The TP@HSA NP hydrogel had a gelation temperature of 30.5 ± 0.2 °C, which allows for its injection at low temperatures and its sol–gel transformation under physiological conditions within 2 min, making it a suitable drug depot. The TP@HSA NP hydrogel was intra-articularly injected into CIA mice; it released TP locally and exerted anti-inflammatory and immunomodulatory effects, alleviating synovial inflammation and cartilage damage effectively. Conclusions: We successfully fabricated a TP@HSA NP-loaded thermosensitive hydrogel with good biosafety, which can release TP slowly for the treatment of RA. Our study provides a basis for the development of TP-based innovative preparations and has good application prospects. Full article

Background: Activating the cytosolic innate immune sensor, the cGAS-STING pathway, holds great promise for enhancing antitumor immunity, particularly in combination with immune checkpoint inhibitors (ICIs). However, the clinical application of STING agonists is often hindered by poor tumor accumulation, limited cellular uptake, and rapid clearance. To address these challenges, we developed a human serum albumin (HSA)-based nanoreactor system for the efficient delivery of the STING agonist SR-717, aiming to improve its antitumor efficacy. Methods: Using a biomineralization technique, we encapsulated SR-717 within HSA nanocages to form SH-NPs. These nanoparticles were characterized in terms of size, stability, and cellular uptake, and their ability to activate the STING pathway was assessed in both in vitro and in vivo models, including freshly isolated human renal tumor tissues. In vivo antitumor efficacy was evaluated in a murine renal tumor model, and immune responses were measured. Results: SH-NPs exhibited enhanced stability, efficient cellular uptake, and superior tumor accumulation compared to free SR-717. They robustly activated the STING pathway, as evidenced by increased phosphorylation of TBK1 and IRF3, along with elevated IFN-β production. Additionally, SH-NPs reshaped the immunosuppressive tumor microenvironment, promoting T-cell-mediated immunity and improving the therapeutic efficacy of checkpoint blockade in murine models. The validation in human renal tumor tissues further highlighted their potential for clinical translation. Importantly, SH-NPs were well tolerated with minimal systemic toxicity. Conclusions: This study underscores the potential of HSA-based nanoparticles for the targeted delivery of STING agonists, effectively enhancing antitumor immunity and improving cancer immunotherapy outcomes. SH-NPs offer a promising solution to the limitations of current STING agonists in clinical settings. Full article

Calcified aortic valve disease in its final stage leads to aortic valve stenosis, limiting cardiac function. To date, surgical intervention is the only option for treating calcific aortic valve stenosis. This study combined controlled drug delivery by nanoparticles (NPs) and active targeting by antibody conjugation. The chelating agent diethylenetriaminepentaacetic acid (DTPA) was covalently bound to human serum albumin (HSA)-based NP, and the NP surface was modified using conjugating antibodies (anti-elastin or isotype IgG control). Calcification was induced ex vivo in porcine aortic valves by preincubation in an osteogenic medium containing 2.5 mM sodium phosphate for five days. Valve calcifications mainly consisted of basic calcium phosphate crystals. Calcifications were effectively resolved by adding 1–5 mg DTPA/mL medium. Incubation with pure DTPA, however, was associated with a loss of cellular viability. Reversal of calcifications was also achieved with DTPA-coupled anti-elastin-targeted NPs containing 1 mg DTPA equivalent. The addition of these NPs to the conditioned media resulted in significant regression of the valve calcifications compared to that in the IgG-NP control without affecting cellular viability. These results represent a step further toward the development of targeted nanoparticular formulations to dissolve aortic valve calcifications. Full article

Circular dichroism (CD) is an excellent and rapid method for analysis of chiral molecules, whose mechanism is based on the absorption of left- and right-hand circularly polarized light. Albumin nanoparticles are biocompatible and easy to modify due to their structure. Tumor cell membranes are among the molecules that direct nanoparticles into the tumor microenvironment, but methods to study them except molecular biology are not well validated yet. The aim of this study was to use circular dichroism as the tool to qualitatively assess ligand binding on the surface of nanoparticles. Human serum albumin (HSA) nanoparticles with encapsulated 5-fluorouracil (5-FU) were coated on MCF-7 cell membranes and subjected to CD analysis. This study was completed using sample and separate 5-FU release analysis. The amount of encapsulated drug in nanoparticles affects the binding of cell membranes on the nanoparticle surface. In addition, it can be suspected that the alpha structure of HSA was mainly used for the interaction, which confirms the effectiveness of using CD as a rapid technique for analyzing ligand-nanoparticle interactions. The release of 5-FU from the nanoparticles proceeds in an uncontrolled manner, making this study in need of further modification and investigation. Full article

The objective of this study was to evaluate the effectiveness of organ-on-chip system investigating simultaneous cellular efficacy and real-time reactive oxygen species (ROS) occurrence of anticancer drug-loaded nanoparticles (NPs) using hepatocarcinoma cells (HepG2) chip system under static and hepatomimicking shear stress conditions (5 dyne/cm²). Then, the role of hepatomimetic shear stress exposed to HepG2 and drug solubility were compared. The highly soluble doxorubicin (DOX) and poorly soluble paclitaxel (PTX) were chosen. Fattigated NPs (AONs) were formed via self-assembly of amphiphilic albumin (HSA)-oleic acid conjugate (AOC). Then, drug-loaded AONs (DOX-AON or PTX-AON) were exposed to a serum-free HepG2 medium at 37 °C and 5% carbon dioxide for 24 h using a real-time ROS sensor chip-based microfluidic system. The cellular efficacy and simultaneous ROS occurrence of free drugs and drug-loaded AONs were compared. The cellular efficacy of drug-loaded AONs varied in a dose-dependent manner and were consistently correlated with real-time of ROS occurrence. Drug-loaded AONs increased the intracellular fluorescence intensity and decreased the cellular efficacy compared to free drugs under dynamic conditions. The half-maximal inhibitory concentration (IC₅₀) values of free DOX (13.4 μg/mL) and PTX (54.44 μg/mL) under static conditions decreased to 11.79 and 38.43 μg/mL, respectively, under dynamic conditions. Furthermore, DOX- and PTX-AONs showed highly decreased IC₅₀ values of 5.613 and 21.86 μg/mL, respectively, as compared to free drugs under dynamic conditions. It was evident that cellular efficacy and real-time ROS occurrence were well-correlated and highly dependent on the drug-loaded nanostructure, drug solubility and physiological shear stress. Full article

In this study, we developed an efficient mRNA delivery vehicle by optimizing a lyophilization method for preserving human serum albumin-based nanobubbles (HSA-NBs), bypassing the need for artificial stabilizers. The morphology of the lyophilized material was verified using scanning electron microscopy, and the concentration, size, and mass of regenerated HSA-NBs were verified using flow cytometry, nanoparticle tracking analysis, and resonance mass measurements, and compared to those before lyophilization. The study also evaluated the response of HSA-NBs to 1 MHz ultrasound irradiation and their ultrasound (US) contrast effect. The functionality of the regenerated HSA-NBs was confirmed by an increased expression of intracellularly transferred Gluc mRNA, with increasing intensity of US irradiation. The results indicated that HSA-NBs retained their structural and functional integrity markedly, post-lyophilization. These findings support the potential of lyophilized HSA-NBs, as efficient imaging, and drug delivery systems for various medical applications. Full article