Search Results (182)

Vaccination represents the cornerstone of Newcastle disease control. Nanotechnology offers a promising approach to improve the effectiveness of DNA vaccines, supporting their use as an alternative to conventional platforms. Herein, the Avian Orthoavulavirus 1 (AOAV-1) fusion (F) gene was cloned into a DNA expression plasmid (pDNA). After validating the constructed pDNA-F and confirming robust intracellular protein expression in vitro, three polymeric nanoparticles (NPs)-based formulations were generated using Chitosan (Cs), poly(lactic-co-glycolic) (PLGA), and poly(amidoamine) (PAMAM)-Dendrimers. Physicochemical characterization, stability assessment, and in vitro release analysis confirmed nanoparticle formation and effective DNA incorporation. In vivo experiments were conducted to comparatively evaluate the immunogenicity, particularly the immune priming capacity, and protective efficacy of nanoparticle-based formulations and naked pDNA-F, all tested in parallel at standardized pDNA doses via intranasal (IN) and intramuscular routes. PAMAM-Dendrimers-pDNA-F IM group demonstrated superior efficacy, with 100% survival, the highest post-challenge anamnestic antibody titers, and a pronounced reduction in viral RNA shedding. PLGA-NPs-pDNA-F IN group demonstrated enhanced efficacy, with 90% survival. Naked pDNA-F surpassed the Cs-NPs-pDNA-F in both immune priming and clinical protection, with Cs-NPs-pDNA-F exhibiting the lowest overall performance. These findings highlight that DNA vaccine performance depends on both carrier type and administration route, with PAMAM dendrimers and PLGA enhancing efficacy, whereas chitosan demonstrated reduced efficacy under the tested conditions. Full article

Poly(amidoamine) (PAMAM) dendrimers are widely recognized as versatile nanocarriers due to their tunable architecture and ability to associate with bioactive molecules. In this study, generation 3 PAMAM dendrimers functionalized with triphenylphosphonium (TPP) were employed to investigate the association of structurally related phenolic compounds—caffeic acid, p-coumaric acid, and cinnamic acid—through either covalent conjugation or non-covalent encapsulation. Physicochemical characterization by NMR, dynamic light scattering, and zeta potential measurements revealed the formation of supramolecular aggregates rather than isolated dendrimer units, with hydrodynamic diameters ranging from 127 to 260 nm and positive surface charge across all formulations. Encapsulation efficiencies determined by HPLC reached 93.8% for caffeic acid, 78.9% for p-coumaric acid, and 71% for cinnamic acid, indicating differential association behavior. Molecular dynamics simulations over 1 μs supported these findings, showing stronger and more stable interactions for polar antioxidants, particularly caffeic acid, driven by hydrogen bonding and electrostatic interactions, while cinnamic acid displayed preferential binding in more hydrophobic dendrimer regions. Radical scavenging assays (DPPH• and ABTS•+) demonstrated that all formulations retained antioxidant capacity, although dendrimer association modulated scavenging kinetics. In cellular assays under oxidative stress, free caffeic acid exhibited the strongest immediate reduction of intracellular reactive oxygen species, whereas dendrimer-associated systems showed reduced but significant activity, consistent with decreased solvent accessibility and slower release predicted by simulations. Overall, these results highlight a trade-off between molecular retention and immediate biological efficacy, demonstrating that the mode of association governs antioxidant accessibility and performance. This combined experimental and computational approach provides a mechanistic framework for the rational design of dendrimer-based delivery systems aimed at balancing stability and functional activity. Full article

Background: Cancer is a major health concern that significantly impacts the global population. Selective chemotherapeutic delivery is needed to improve the efficacy of cancer therapy while minimizing side effects in healthy cells. This study investigated the potential of gold nanoclusters (AuNCs) functionalized with poly(amidoamine) dendrimers (PAMAM) and folic acid (FA) to selectively deliver doxorubicin (DOX) to cancer cells that express the folate receptor (FR). Methods: AuNC synthesis was confirmed via UV–visible and Fourier transform infrared spectroscopy, nanoparticle tracking analysis, and transmission electron microscopy. Folic acid (FA) was incorporated for cell surface receptor targeting, while the triphenylphosphonium cation (TPP⁺) was added to improve mitochondrial localization. Cytotoxicity (MTT), apoptosis, caspase 3/7, mitopotential, and oxidative stress assays were assessed using human MCF-7 (breast adenocarcinoma), HeLa (cervical carcinoma), Caco-2 (colon adenocarcinoma), MDA-MB-231 (epithelial breast cancer), and the embryonic kidney (HEK293) cells. Results: Favorable DOX loading (>78%), with more than 90% of the drug released at pH 4.5, was achieved. A dose-dependent increase in cytotoxicity was observed, with IC50 values lower in cancer cells than HEK293 cells, indicating selective toxicity and minimal off-target effects. Targeting nanocomplexes produced the best responses in the mitopotential, caspase, and oxidative stress assays in HeLa and MCF-7 cells. Conclusions: The improved cytotoxicity in cancer cells may be due to folate-receptor-mediated cellular uptake, as well as the mitochondrial uptake of TPP⁺ nanocomplexes. This highlighted the potential of the drug–AuNC nanocomplexes to limit systemic side effects, proposing a potential novel strategy for drug delivery to cancer cells. Full article

HIV-associated neurocognitive impairment persists despite combination antiretroviral therapy, largely driven by chronic microglial activation that sustains neuroinflammation and neuronal injury. Activated microglia contribute to HIV-associated brain pathology by releasing proinflammatory mediators that disrupt synaptic integrity and impair cognition. N-acetylaspartylglutamate (NAAG), an abundant neuropeptide that maintains glutamatergic homeostasis, is hydrolyzed by glutamate carboxypeptidase II (GCPII) to glutamate. We previously demonstrated that reduced brain and cerebrospinal fluid NAAG levels in people living with HIV correlate with cognitive impairment, and that pharmacological GCPII inhibition with 2-(phosphonomethyl)-pentanedioic acid (2-PMPA) elevates brain NAAG and improves cognition in EcoHIV-infected mice. To enhance brain delivery and preferentially target activated microglia, we conjugated 2-PMPA to a generation 4 hydroxyl poly(amidoamine) (PAMAM) dendrimer (D-2-PMPA). Our findings demonstrate that D-2-PMPA achieves preferential microglial drug delivery, resulting in a >600% increase in cerebrospinal fluid NAAG levels. At doses 8.3-fold lower than free 2-PMPA, this formulation reversed EcoHIV-induced deficits in social interaction, novel object recognition, and fear-conditioned memory without altering locomotor activity or anxiety-like behavior. D-2-PMPA also restored prefrontal cortex synaptic density and preserved dendritic architecture. Together, these findings demonstrate that microglia-targeted GCPII inhibition represents a potent nanotherapeutic strategy to restore synaptic integrity and cognitive function in HIV-associated neurocognitive impairment. Full article

Poly(amidoamine) (PAMAM) and poly-L-lysine (PLL) dendrimers have emerged as highly versatile macromolecular platforms with significant potential in biomedical applications, owing to their well-defined architecture, tunable surface chemistry, and capacity for multivalent functionalization. Their ability to carry substantial molecular payloads and to be engineered for selective interactions with biological systems has positioned them as attractive candidates for targeted drug delivery, including the transport of boron-rich compounds. Recent advances in dendrimer chemistry have enabled the incorporation of boron clusters into PAMAM and PLL structures, creating hybrid systems designed to enhance cellular uptake, improve tumor selectivity, and increase boron accumulation within malignant tissues. Given the growing interest in boron neutron capture therapy (BNCT), the integration of boron clusters into dendrimer structures represents a particularly promising direction for enhancing boron delivery to tumors. This manuscript reviews current knowledge on PAMAM and PLL dendrimers and their boron-functionalized derivatives, summarizing findings from cell culture studies, in vivo models, and clinical or preclinical investigations. Particular attention is given to both the advantageous properties of these dendrimers—such as improved delivery efficiency and biocompatibility—and their potential undesirable biological effects. As such, PAMAM and PLL dendrimers represent an important and evolving class of carriers that may significantly advance the effectiveness of boron neutron capture therapy (BNCT) in cancer treatment. Full article

Studying nanoscale self-assembly in real time using external stimuli unlocks new opportunities for dynamic and adaptive materials. While electrostatic self-assembly is well-established, real-time monitoring of its structural evolution under light irradiation remains largely unexploited. In this study, we employ light-responsive azobenzene dyes (Acid Yellow 38, AY38) and pH-sensitive polyamidoamine (PAMAM) dendrimers to investigate the kinetics of electrostatic self-assembly under UV irradiation. Using a custom in situ small-angle neutron scattering (SANS) setup, we track the real-time morphological transformations of self-assembled structures with sub-minute resolution. We introduce two distinct pathways: method A (pre-irradiated cis-AY38 for controlled, slow kinetics) and method B (direct UV-induced self-assembly, fast kinetics). The results reveal that trans-cis isomerization kinetics dictate the rate of self-assembly, influencing aggregate stability, ζ-potential evolution, and final morphology. Structural analysis using dynamic and static light scattering (DLS and SLS) and SANS elucidates a transition from spherical to ellipsoidal morphologies governed by electrostatic and dipole-dipole interactions. These findings establish photoisomerization-driven self-assembly as a robust mechanism for tunable nanoscale architectures, paving the way for adaptive photonic materials, targeted drug delivery, and reconfigurable nanostructures. Full article

The article describes the interaction between 4-amino-1,8-naphthalic anhydride and the terminal amine groups of the first-generation poly(amidoamine) (PAMAM) dendrimer. Cotton fabric was treated with the newly obtained photoactive dendrimer (DA) to achieve its antimicrobial photodynamic inactivation. The photodynamic inactivation method is an innovative approach in which, upon irradiation with visible light, photosensitizers generate highly reactive oxygen species, specifically singlet oxygen (¹O₂), which destroys microbial cells. In the dark, the DA dendrimer strongly inhibits the development of the model bacteria Bacillus cereus (a Gram-positive bacterium) and Pseudomonas aeruginosa (a Gram-negative bacterium) in solution. Upon irradiation with visible light, the inhibition is significantly enhanced, achieving almost complete inactivation of B. cereus and 94% of P. aeruginosa. Cotton fabric was treated with the DA dendrimer at two concentrations (0.15% and 0.30% weight of fabric). It was found that the dendrimer molecules are adherent to the cellulose fiber surfaces and do not leach in washing. Treatment of the fabric with DA partially increases its hydrophobicity, which prevents the adhesion of some bacteria. In the dark, the treated fabric shows weak antibacterial activity because the dendrimer DA molecules are attached to the textile surface, and inactivation depends solely on the microorganism’s surface contact. However, upon irradiation, a significant increase in the fabric’s antimicrobial activity is observed, as the fixed dendrimer participates in the release of singlet oxygen, which effectively attacks microorganism cell membranes and components. For the fabric with the higher concentration (DA30), 94% inactivation of B. cereus and 89% inactivation of P. aeruginosa were achieved. Thus, a synergistic effect between photodynamic activity and increased hydrophobicity was achieved, making the modified cotton fabric an example of a high-tech textile with permanent, renewable disinfection. Full article

This study presents a novel hydrogel formulation combining mupirocin, a broad-spectrum antibiotic, with keratinocyte growth factor (KGF) to enhance wound healing through antibacterial action and tissue regeneration. Mupirocin was encapsulated in hydroxypropyl β-cyclodextrin (HP-β-CD) and stabilized with poly(amidoamine) dendrimers (PAMAM). Molecular docking studies assessed mupirocin’s binding to PAMAM and its interaction with isoleucyl-tRNA synthetase. Physicochemical properties—including zeta potential, particle size, and surface tension—were characterized, and drug release kinetics were evaluated using Franz diffusion cells. In vitro assays on human dermal fibroblasts (HS27) included proliferation, scratch wound healing, and flow cytometry to assess cellular behavior. Antibacterial efficacy was determined via the Kirby–Bauer disk diffusion method. Results showed strong binding of mupirocin to its target enzyme, enhanced by KGF. The hydrogel exhibited favorable properties: surface tension of 24.7 dyne/cm, zeta potential of −24.79 mV, and particle size of ~119 nm, indicating high stability. Franz diffusion revealed sustained drug release compared to commercial mupirocin. Cellular assays demonstrated significant fibroblast migration and proliferation, with flow cytometry confirming increased wound healing markers. The formulation showed potent antimicrobial activity, including against Methicillin-resistant Staphylococcus aureus (MRSA), highlighting its promise for infected wound treatment and advanced clinical wound care. Full article

The rapid development of nanomedicine is driving extensive research and the synthesis of new nanomaterials. Biocompatible nanoparticles have the potential to serve as both imaging agents for medical diagnostics and carriers for targeted therapy. Among the various nanocomplexes investigated for cancer theranostics, gold nanoparticles stabilized by polyamidoamine (PAMAM) dendrimers have proven to be a promising platform. The unique physicochemical properties of gold nanoparticles, when combined with the branched architecture of PAMAM dendrimers, enhance stability, biocompatibility, and functionalization capability, enabling precise tumour targeting, improved imaging contrast, and controlled drug release. In this paper, we demonstrate the synthesis of gold nanoparticles stabilized by 2nd generation PAMAM dendrimers using three different methods: sonication, microwave, and unassisted techniques. The described synthesis approaches provide a rapid and straightforward method to achieve monodisperse particle size distribution and high colloidal stability up to 3 months. Physicochemical characterization of the nanocomplexes was carried out using ultraviolet-visible light spectroscopy, dynamic light scattering with zeta potential analysis, infrared spectroscopy, and atomic force microscopy. Furthermore, the effects of selected concentrations of PAMAM:HAuCl₄ nanoparticles for all types of synthesis on human breast adenocarcinoma and human osteosarcoma cell lines were investigated using cytotoxicity assays. The results of the conducted tests show cytotoxicity values at a similar level. However, the sample synthesized using the sonication technique exhibited the lowest toxicity. Full article

Background/Objectives: Alectinib, a second-generation tyrosine kinase inhibitor indicated for the treatment of non-small-cell lung cancer (NSCLC), exhibits suboptimal oral bioavailability, primarily attributable to its inherently low aqueous solubility and limited dissolution kinetics. This study aimed to enhance Alectinib’s solubility and therapeutic efficacy by formulating a G4-NH2-PAMAM dendrimer complex. Methods: The complex was prepared using the organic solvent evaporation method and characterized by DSC, FTIR, dynamic light scattering (DLS), and zeta potential measurements. A validated high-performance liquid chromatography (HPLC) method quantified the Alectinib. In vitro drug release studies compared free Alectinib with the G4-NH2-PAMAM dendrimer complex. Cytotoxicity against NSCLC cell line A549 was assessed using MTT assays, clonogenic assay, and scratch-wound assay. Xenograft effect was investigated in the H460 lung cell line. Pharmacokinetic parameters were evaluated in rats using LC–MS/MS. Results: Alectinib exhibited an encapsulation efficiency of 59 ± 5%. In vitro release studies demonstrated sustained drug release at pH 6.8 and faster degradation at pH 2.5. Anticancer activity in vitro showed comparable efficacy to free Alectinib, with 98% migration inhibition. In vivo tumor suppression studies revealed near-complete tumor regression (~100%) after 17 days of treatment, compared to 75% with free Alectinib. Pharmacokinetic analysis indicated enhanced absorption (shorter Tmax), prolonged systemic circulation (longer half-life), and higher bioavailability (increased AUC) for the dendrimer-complexed drug. Conclusions: These findings suggest that the G4-NH2-PAMAM dendrimer system significantly improves Alectinib’s pharmacokinetics and therapeutic potential, making it a promising approach for NSCLC treatment. Full article

Gold nanoparticles stabilized with polyamidoamine dendrimers are one of the potential candidates for use as a contrast agent in computed tomography and a drug delivery agent. This work demonstrates a rapid, two-step synthesis of such complexes, which are size-stable for up to 18 months. The first step of the synthesis involves a short sonication of gold (III) chloride hydrate with polyamidoamine dendrimers of the fourth generation, while the second step uses microwaves to reduce gold (III) chloride hydrate with sodium citrate. The developed synthesis method enables rapid production of spherical and monodisperse gold nanoparticles stabilized with polyamidoamine dendrimers. Physicochemical characterization of the gold nanoparticle-polyamidoamine dendrimers complexes was performed using ultraviolet-visible spectroscopy, dynamic light scattering technique, infrared spectroscopy, atomic force microscopy, and transmission electron microscopy. The toxicity of synthesized complexes on the breast cancer MCF-7 cell line has been studied using the tetrazolium salt reduction test. The produced gold nanoparticles revealed lower toxicity levels on the MCF-7 cell line after 18 months from synthesis compared with newly synthesized colloids. Synthesized gold nanoparticles stabilized with dendrimers and commercially available gold nanoparticles stabilized with sodium citrate show similar toxicity levels on breast cancer cells. Full article

Polyhydroxyalkanoates (PHAs), recognized as a medical biomaterial, have been proven to promote cell proliferation and tissue repair. PHA has a variety of forms: PHB, PHV, PHHx, and PHBHHx, etc. In this study, PHBHHx was selected as the precursor to fabricate biopolyester films. Specifically, a novel type of biopolyester film was generated through an ammonolysis cross-linking reaction in conjunction with polyamidoamine dendrimer G2.0 (PAMAM). The properties of the resultant biopolyester films were comprehensively evaluated, encompassing surface characteristics, amino group content, and water contact angle. The drug-loading properties and compatibility with osteoblasts of the biopolyester films were also determined. The findings revealed that following aminolysis, the biopolyester film surface exhibited enhanced roughness and an enlarged surface area. Moreover, as the aminolysis duration extended, the hydrophilicity and drug-loading efficiency were significantly augmented. Post-aminolysis, the PHBHHx membrane exhibited a more favorable environment for the adhesion and proliferation of osteoblasts. Overall, the biopolyester film developed in this study provides novel insights and materials for tissue engineering, especially bone tissue repair. Full article

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a well-known technique for polymer analysis, particularly for determining the molecular weight and structural details of dendrimers. In this study, we evaluated the performance of various matrices, such as 2′,4′,6′-trihydroxyacetophenone (THAP), α-cyano-4-hydroxycinnamic acid (HCCA), and sinapinic acid (SA), and their combinations, on the sensitivity and resolution of poly(amidoamine) (PAMAM) dendrimers of different generations (G3.0, G4.0, and G5.0). Our results demonstrated that the combination of HCCA-THAP significantly enhanced spectral resolution and peak intensity compared to individual matrices, particularly for higher-generation dendrimers. This improvement is attributed to the better ionization efficiency achieved with the combined matrices. These findings provide critical insights into optimizing MALDI-TOF MS for the accurate characterization of complex polymers, with potential applications in drug delivery and nanotechnology. Full article

A novel electrochemical detection method utilizing a cost-effective hybrid-modified electrode has been established. A glassy carbon (GC) modified electrode was tested for its ability to measure electrochemical tTG antibody levels, which are essential for diagnosing and monitoring Celiac disease (CD). Tissue transglutaminase protein biomolecules are immobilized on a quantum dots-polypyrrole nanocomposite in the improved electrode. Initial, quantum dots (QDs) were obtained from Bombyx mori silk fibroin and embedded in polypyrrole film. Using carbodiimide coupling, a polyamidoamine (PAMAM) dendrimer was linked with GQDs-polypyrrole film to improve sensor sensitivity. The tissue transglutaminase (tTG) antigen was cross-linked onto PAMAM using N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC)-N-hydroxy succinimide (NHS) chemistry to develop a nanoprobe that can detect human serum anti-tTG antibodies. The physicochemical characteristics of the synthesized nanocomposite were examined by FTIR, UV-visible, FE-SEM, EDX, and electrochemical studies. The novel electrode measures anti-tissue antibody levels in real time using human blood serum samples. The modified electrode has great repeatability and an 8.7 U/mL detection limit. Serum samples from healthy people and CD patients were compared to standard ELISA kit assays. SPSS and Excel were used for statistical analysis. The improved electrode and detection system can identify anti-tissue antibodies up to 80 U/mL. Full article

pH-responsive polyamidoamine (PAMAM) dendrimers are used as well-defined building blocks to design light-switchable nano-assemblies in solution. The complex interplay between the photoresponsive di-anionic azo dye Acid Yellow 38 (AY38) and the cationic PAMAM dendrimers of different generations is presented in this study. Electrostatic self-assembly involving secondary dipole–dipole interactions provides well-defined assemblies within a broad size range (10 nm–1 μm) with various shapes. The size and shape of these assemblies were determined using dynamic and static light scattering (DLS/SLS) and small-angle neutron scattering (SANS); ζ-potential measurements were performed to elucidate the charge characteristics, revealing the effective surface charge density of the nano-objects as an important parameter in the size and shape control. UV–vis spectroscopy and isothermal titration calorimetry (ITC) were employed to investigate the interaction on a molecular level and from a thermodynamic point of view. The results show that the amount of isomerized cis dye depends on the dendrimer generation because of a photoprotective effect through electrostatics for lower generations and through dipole–dipole interactions for higher generations; as the cis dye and trans dye bind with different strength, the amount of cis dye then again encodes the charge density and thereby the particle size and shape. Full article