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Ageing Research Reviews Jun 2024Alzheimer's disease (AD) stands as a formidable challenge in modern medicine, characterized by progressive neurodegeneration, cognitive decline, and memory impairment.... (Review)
Review
Alzheimer's disease (AD) stands as a formidable challenge in modern medicine, characterized by progressive neurodegeneration, cognitive decline, and memory impairment. Despite extensive research, effective therapeutic strategies remain elusive. The antioxidant, anti-inflammatory, and neuroprotective properties of curcumin, found in turmeric, have demonstrated promise. The poor bioavailability and rapid systemic clearance of this drug limit its clinical application. This comprehensive review explores the potential of curcumin-loaded polymeric nanomaterials as an innovative therapeutic avenue for AD. It delves into the preparation and characteristics of diverse polymeric nanomaterial platforms, including liposomes, micelles, dendrimers, and polymeric nanoparticles. Emphasis is placed on how these platforms enhance curcumin's bioavailability and enable targeted delivery to the brain, addressing critical challenges in AD treatment. Mechanistic insights reveal how these nanomaterials modulate key AD pathological processes, including amyloid-beta aggregation, tau phosphorylation, oxidative stress, and neuroinflammation. The review also highlighted the preclinical studies demonstrate reduced amyloid-beta plaques and neuroinflammation, alongside improved cognitive function, while clinical trials show promise in enhancing curcumin's bioavailability and efficacy in AD. Additionally, it addresses the challenges of clinical translation, such as regulatory issues, large-scale production, and long-term stability. By synthesizing recent advancements, this review underscores the potential of curcumin-loaded polymeric nanomaterials to offer a novel and effective therapeutic approach for AD, aiming to guide future research and development in this field.
PubMed: 38925479
DOI: 10.1016/j.arr.2024.102393 -
Gels (Basel, Switzerland) May 2024Osteoclast stimulatory transmembrane protein (OC-STAMP) plays a pivotal role in the promotion of cell fusion during osteoclast differentiation (osteoclastogenesis) in...
Osteoclast stimulatory transmembrane protein (OC-STAMP) plays a pivotal role in the promotion of cell fusion during osteoclast differentiation (osteoclastogenesis) in the context of pathogenic bone resorption. Thus, it is plausible that the suppression of OC-STAMP through a bioengineering approach could lead to the development of an effective treatment for inflammatory bone resorptive diseases with minimum side effects. Here, we synthesized two types of spermine-bearing (Spe) cationic glucan dendrimer (GD) gels (with or without C12) as carriers of short interfering RNA (siRNA) to silence OC-STAMP. The results showed that amphiphilic C12-GD-Spe gel was more efficient in silencing OC-STAMP than GD-Spe gel and that the mixture of anti-OC-STAMP siRNA/C12-GD-Spe significantly downregulated RANKL-induced osteoclastogenesis. Also, local injection of anti-OC-STAMP-siRNA/C12-GD-Spe could attenuate bone resorption induced in a mouse model of periodontitis. These results suggest that OC-STAMP is a promising target for the development of a novel bone regenerative therapy and that C12-GD-Spe gel provides a new nanocarrier platform of gene therapies for osteolytic disease.
PubMed: 38920924
DOI: 10.3390/gels10060377 -
ACS Macro Letters Jun 2024Random difunctionalization of dendrimer surfaces, frequently employed in biological applications, provides the advantage of dual functional groups through a synthetic...
Random difunctionalization of dendrimer surfaces, frequently employed in biological applications, provides the advantage of dual functional groups through a synthetic pathway that is simpler compared to precise difunctionalization. However, is the random difunctionalization as efficient as the precise difunctionalization on the surface of dendrimers? This question is unanswered to date because most dendrimer families face challenges in achieving precise functionalization. Polyphosphorhydrazone (PPH) dendrimers present a unique opportunity to obtain precise difunctionalization at each terminal branching point. The work concerning catalysis we report with PPH dendrimers, whether precisely or randomly functionalized, addresses this question. Across PPH dendrimers, from generations 1 to 3, precise functionalization consistently outperforms random functionalization in terms of efficiency. This finding introduces a novel concept in dendrimer science, emphasizing the superiority of precise over random functionalization methodologies. Introducing a groundbreaking concept in the field of dendrimers.
PubMed: 38917088
DOI: 10.1021/acsmacrolett.4c00204 -
Journal of Biomaterials Science.... Jun 2024The main objective of this work is to synthesize multifunctional nanodendritic structural molecules that can effectively encapsulate hydrophilic as well as hydrophobic...
The main objective of this work is to synthesize multifunctional nanodendritic structural molecules that can effectively encapsulate hydrophilic as well as hydrophobic therapeutic agents. Four different types of fourth-generation lysine-citric acid based dendrimer have been synthesized in this work: PE-MC-Lys-CA-PEG, TMP-MC-Lys-CA-PEG, PE-MS-Lys-CA-PEG, and TMP-MS-Lys-CA-PEG. The antibacterial drug cefotaxime (CFTX) was further conjugated to these dendrimers. The dendrimer and drug-dendrimer conjugate structures were characterized with the help of FTIR,H-NMR, and C-NMR spectroscopy. Zeta sizer, AFM, and HR-TEM techniques were used to investigate the particle size, surface topography, and structural characteristics of drug-dendrimer conjugates. drug release was then investigated using dialysis method. Various kinetic drug release models were examined to evaluate the type of kinetic drug release mechanism of the formulations. Cytotoxicity study revealed that the dendrimers encapsulated with CFTX exhibited 2-3% toxicity against healthy epithelial cells, indicating their safe use. Plain dendrimers show 10-15% hemolytic toxicity against red blood cells (RBC), and the toxicity was reduced to 2-3% when CFTX was conjugated to the same dendrimers. The 3 and 4 generation synthesized drug-dendrimer conjugates exhibit a significantly effective zone of inhibition (ZOI) against both Gram-positive and Gram-negative bacteria. For Gram-positive bacteria, the lower concentration of 0.1 mg/mL showed more than 98% inhibition of drug-dendrimer conjugate samples against and more than 50% inhibition against using 0.2 mg/mL, respectively. Moreover, samples with concentrations of 0.5 and 1.0 mg/mL exhibited more than 50% inhibition against and , respectively.
PubMed: 38910561
DOI: 10.1080/09205063.2024.2362023 -
Biotechnology Advances Jun 2024Nucleic acid therapy is currently the most promising method for treating tumors and genetic diseases and for preventing infectious diseases. However, the biggest... (Review)
Review
Nucleic acid therapy is currently the most promising method for treating tumors and genetic diseases and for preventing infectious diseases. However, the biggest obstacle to this therapy is delivery of the nucleic acids to the target site, which requires overcoming problems such as capture by the immune system, the need to penetrate biofilms, and degradation of nucleic acid performance. Designing suitable delivery vectors is key to solving these problems. Lipids-which consist of a hydrophilic headgroup, a linker, and a hydrophobic tail-are crucial components for the construction of vectors. The headgroup is particularly important because it affects the drug encapsulation rate, the vector cytotoxicity, and the transfection efficiency. Herein, we focus on various headgroup structures (tertiary amines, quaternary ammonium salts, peptides, piperazines, dendrimers, and several others), and we summarize and classify important lipid-based carriers that have been developed in recent years. We also discuss applications of cationic lipids with various headgroups for delivery of nucleic acid drugs, and we analyze how headgroup structure affects transport efficiency and carrier toxicity. Finally, we briefly describe the challenges of developing novel lipid carriers, as well as their prospects.
PubMed: 38906496
DOI: 10.1016/j.biotechadv.2024.108395 -
Analytical Chemistry Jun 2024Herein, CsPbBr perovskite quantum dots (CPB PQDs)@poly(methyl methacrylate) (PMMA) (CPB@PMMA) nanospheres were used as energy donors with high Förster resonance energy...
Herein, CsPbBr perovskite quantum dots (CPB PQDs)@poly(methyl methacrylate) (PMMA) (CPB@PMMA) nanospheres were used as energy donors with high Förster resonance energy transfer (FRET) efficiency and exceptional biocompatibility for ultrasensitive dynamic imaging of tiny amounts of microRNAs in living cells. Impressively, compared with traditional homogeneous single QDs as energy donors, CPB@PMMA obtained by encapsulating numerous CPB PQDs into PMMA as energy donors could not only significantly increase the efficiency of FRET via improving the local concentration of CPB PQDs but also distinctly avoid the problem of cytotoxicity caused by divulged heavy metal ions entering living cells. Most importantly, in the presence of target miRNA-21, DNA dendrimer-like nanostructures labeled with 6-carboxy-tetramethylrhodamine (TAMRA) were generated by the exposed tether interhybridization of the Y-shape structure, which could wrap around the surface of CPB@PMMA nanospheres to remarkably bridge the distance of FRET and increase the opportunity for effective energy transfer, resulting in excellent precision and accuracy for ultrasensitive and dynamic imaging of miRNAs. As proof of concept, the proposed strategy exhibited ultrahigh sensitivity with a detection limit of 45.3 aM and distinctly distinguished drug-irritative miRNA concentration abnormalities with living cells. Hence, the proposed enzyme-free CPB@PMMA biosensor provides convincing evidence for supplying accurate information, which could be expected to be a powerful tool for bioanalysis, diagnosis, and prognosis of human diseases.
PubMed: 38898770
DOI: 10.1021/acs.analchem.4c01833 -
International Journal of Molecular... May 2024Peptides displaying antimicrobial properties are being regarded as useful tools to evade and combat antimicrobial resistance, a major public health challenge. Here we...
Peptides displaying antimicrobial properties are being regarded as useful tools to evade and combat antimicrobial resistance, a major public health challenge. Here we have addressed dendrimers, attractive molecules in pharmaceutical innovation and development displaying broad biological activity. Triazine-based dendrimers were fully synthesized in the solid phase, and their antimicrobial activity and some insights into their mechanisms of action were explored. Triazine is present in a large number of compounds with highly diverse biological targets with broad biological activities and could be an excellent branching unit to accommodate peptides. Our results show that the novel peptide dendrimers synthesized have remarkable antimicrobial activity against Gram-negative bacteria ( and ) and suggest that they may be useful in neutralizing the effect of efflux machinery on resistance.
Topics: Dendrimers; Triazines; Microbial Sensitivity Tests; Escherichia coli; Pseudomonas aeruginosa; Antimicrobial Peptides; Anti-Bacterial Agents; Anti-Infective Agents; Antimicrobial Cationic Peptides
PubMed: 38892071
DOI: 10.3390/ijms25115883 -
Polymers May 2024Phenanthrenequinone-doped poly(methyl methacrylate) (PQ/PMMA) photopolymers are potential holographic storage media owing to their high-density storage capacities, low...
Phenanthrenequinone-doped poly(methyl methacrylate) (PQ/PMMA) photopolymers are potential holographic storage media owing to their high-density storage capacities, low costs, high stability, and negligible shrinkage in volume holographic permanent memory. However, because of the limitations of the substrate, conventional Plexiglas materials do not exhibit a good performance in terms of photosensitivity and molding. In this study, the crosslinked structure of PMMA was modified by introducing a dendrimer monomer, pentaerythritol tetraacrylate (PETA), which increases the photosensitivity of the material 2 times (from ~0.58 cm/J to ~1.18 cm/J), and the diffraction efficiency is increased 1.6 times (from ~50% to ~80%). In addition, the modified material has a superior ability to mold compared to conventional materials. Moreover, the holographic performance enhancement was evaluated in conjunction with a quantum chemical analysis. The doping of PETA resulted in an overall decrease in the energy required for the reaction system of the material, and the activation energy decreased by ~0.5 KJ/mol in the photoreaction stage.
PubMed: 38891431
DOI: 10.3390/polym16111484 -
Foods (Basel, Switzerland) Jun 2024Curcumin, a hydrophobic polyphenol extracted from the rhizome of , is now considered a candidate drug for the treatment of neurological diseases, including Parkinson's... (Review)
Review
Curcumin, a hydrophobic polyphenol extracted from the rhizome of , is now considered a candidate drug for the treatment of neurological diseases, including Parkinson's Disease (PD), Alzheimer's Disease (AD), Huntington's Disease (HD), Multiple Sclerosis (MS), Amyotrophic Lateral Sclerosis (ALS), and prion disease, due to its potent anti-inflammatory, antioxidant potential, anticancerous, immunomodulatory, neuroprotective, antiproliferative, and antibacterial activities. Traditionally, curcumin has been used for medicinal and dietary purposes in Asia, India, and China. However, low water solubility, poor stability in the blood, high rate of metabolism, limited bioavailability, and little capability to cross the blood-brain barrier (BBB) have limited the clinical application of curcumin, despite the important pharmacological activities of this drug. A variety of nanocarriers, including liposomes, micelles, dendrimers, cubosome nanoparticles, polymer nanoparticles, and solid lipid nanoparticles have been developed with great success to effectively deliver the active drug to brain cells. Functionalization on the surface of nanoparticles with brain-specific ligands makes them target-specific, which should significantly improve bioavailability and reduce harmful effects. The aim of this review is to summarize the studies on curcumin and/or nanoparticles containing curcumin in the most common neurodegenerative diseases, highlighting the high neuroprotective potential of this nutraceutical.
PubMed: 38891002
DOI: 10.3390/foods13111774 -
Small (Weinheim An Der Bergstrasse,... Jun 2024Acute lung injury (ALI) is the pathophysiological precursor of acute respiratory distress syndrome. It is characterized by increased oxidative stress and exaggerated...
Acute lung injury (ALI) is the pathophysiological precursor of acute respiratory distress syndrome. It is characterized by increased oxidative stress and exaggerated inflammatory response that disrupts redox reactions and immune homeostasis in the lungs, thereby posing significant clinical challenges. In this study, an internally functionalized thioether-enriched dendrimer Sr-G4-PEG is developed, to scavenge both proinflammatory cytokines and reactive oxygen species (ROS) and restore homeostasis during ALI treatment. The dendrimers are synthesized using an efficient and orthogonal thiol-ene "click" chemistry approach that involves incorporating thioether moieties within the dendritic architectures to neutralize the ROS. The ROS scavenging of Sr-G4-PEG manifests in its capacity to sequester proinflammatory cytokines. The synergistic effects of scavenging ROS and sequestering inflammatory cytokines by Sr-G4-PEG contribute to redox remodeling and immune homeostasis, along with the modulation of the NLRP3-pyroptosis pathway. Treatment with Sr-G4-PEG enhances the therapeutic efficacy of ALIs by alleviating alveolar bleeding, reducing inflammatory cell infiltration, and suppressing the release of inflammatory cytokines. These results suggest that Sr-G4-PEG is a potent nanotechnological candidate for remodeling redox and immune homeostasis in the treatment of ALIs, demonstrating the great potential of dendrimer-based nanomedicine for the treatment of respiratory pathologies.
PubMed: 38888130
DOI: 10.1002/smll.202402146