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Dalton Transactions (Cambridge, England... May 2024The field of supported catalysis has experienced increased attention with respect to the development of novel architectures for immobilizing catalytic species, aiming to...
The field of supported catalysis has experienced increased attention with respect to the development of novel architectures for immobilizing catalytic species, aiming to maintain or enhance their activity while facilitating the easy recovery and reuse of the active moiety. Dendrimers have been identified as promising candidates capable of imparting such properties to catalysts through selective functionalization. The present study details the synthesis of two polyphosphorhydrazone (PPH) dendrons, each incorporating azide or acetylene groups at the core for subsequent coupling through "click" triazole chemistry. Employing this methodology, a novel PPH Janus dendrimer was successfully synthesized, featuring ten polyethylene glycol (PEG) chains on one side of the structure and ten Ru(-cymene) derivatives on the other. This design was intended to confer dual properties, influencing solubility modulation, and allowing the presence of active catalytic moieties. The synthesized dendrimer underwent testing in the isomerization of allyl alcohols in organic solvents and biphasic solvent mixtures. The results demonstrated a positive dendritic effect compared with model monometallic and bimetallic species, providing a proof-of-concept for the first PPH Janus dendrimer with tested applications in catalysis.
PubMed: 38738979
DOI: 10.1039/d3dt04376b -
Cureus Apr 2024Cardiovascular diseases (CVDs) are a leading cause of death globally, demanding innovative therapeutic strategies. Nanoformulations, including nanoparticles, address... (Review)
Review
Cardiovascular diseases (CVDs) are a leading cause of death globally, demanding innovative therapeutic strategies. Nanoformulations, including nanoparticles, address challenges in drug delivery, stem cell therapy, imaging, and gene delivery. Nanoparticles enhance drug solubility, bioavailability, and targeted delivery, with gas microbubbles, liposomal preparations, and paramagnetic nanoparticles showing potential in treating atherosclerosis and reducing systemic side effects. In stem cell therapy, nanoparticles improve cell culture, utilizing three-dimensional nanofiber scaffolds and enhancing cardiomyocyte growth. Gold nanoparticles and poly(lactic-co-glycolic acid) (PLGA)-derived microparticles promote stem cell survival. Stem cell imaging utilizes direct labeling with nanoparticles for magnetic resonance imaging (MRI), while optical tracking employs dye-conjugated nanoparticles. In gene delivery, polymeric nanoparticles like polyethylenimine (PEI) and dendrimers, graphene-based carriers, and chitosan nanoparticles offer alternatives to virus-mediated gene transfer. The potential of magnetic nanoparticles in gene therapy is explored, particularly in hepatocellular carcinoma. Overall, nanoparticles have transformative potential in cardiovascular disease management, with ongoing research poised to enhance clinical outcomes.
PubMed: 38738046
DOI: 10.7759/cureus.58059 -
ACS Applied Materials & Interfaces May 2024Tumor-associated macrophages (TAMs) usually adopt a tumor-promoting M2-like phenotype, which largely impedes the immune response and therapeutic efficacy of solid...
Tumor-associated macrophages (TAMs) usually adopt a tumor-promoting M2-like phenotype, which largely impedes the immune response and therapeutic efficacy of solid tumors. Repolarizing TAMs from M2 to the antitumor M1 phenotype is crucial for reshaping the tumor immunosuppressive microenvironment (TIME). Herein, we developed self-assembled nanoparticles from the polymeric prodrug of resiquimod (R848) to reprogram the TIME for robust cancer immunotherapy. The polymeric prodrug was constructed by conjugating the R848 derivative to terminal amino groups of the linear dendritic polymer composed of linear poly(ethylene glycol) and lysine dendrimer. The amphiphilic prodrug self-assembled into nanoparticles (PLRS) of around 35 nm with a spherical morphology. PLRS nanoparticles could be internalized by antigen-presenting cells (APCs) and thus efficiently repolarized macrophages from M2 to M1 and facilitated the maturation of APCs. In addition, PLRS significantly inhibited tumor growth in the 4T1 orthotopic breast cancer model with much lower systemic side effects. Mechanistic studies suggested that PLRS significantly stimulated the TIME by repolarizing TAMs into the M1 phenotype and increased the infiltration of cytotoxic T cells into the tumor. This study provides an effective polymeric prodrug-based strategy to improve the therapeutic efficacy of R848 in cancer immunotherapy.
Topics: Prodrugs; Animals; Mice; Immunotherapy; Imidazoles; Nanoparticles; Female; Mice, Inbred BALB C; Cell Line, Tumor; Humans; Tumor-Associated Macrophages; Antineoplastic Agents; RAW 264.7 Cells; Polyethylene Glycols; Tumor Microenvironment; Dendrimers; Macrophages
PubMed: 38735053
DOI: 10.1021/acsami.4c01563 -
Molecules (Basel, Switzerland) Apr 2024A novel second-generation blue fluorescent polyamidoamine dendrimer peripherally modified with sixteen 4--dimethylaninoethyloxy-1,8-naphthalimide units was synthesized....
A novel second-generation blue fluorescent polyamidoamine dendrimer peripherally modified with sixteen 4--dimethylaninoethyloxy-1,8-naphthalimide units was synthesized. Its basic photophysical characteristics were investigated in organic solvents of different polarity. It was found that in these solvents, the dendrimer is colorless and emitted blue fluorescence with different intensities depending on their polarity. The effect of the pH of the medium on the fluorescence intensity was investigated and it was found that in the acidic medium, the fluorescence is intense and is quenched in the alkaline medium. The ability of the dendrimer to detect metal ions (Pb, Zn, Mg, Sn, Ba, Ni, Sn, Mn, Co, Fe, and Al) was also investigated, and it was found that in the presence of Fe, the fluorescent intensity was amplified more than 66 times. The antimicrobial activity of the new compound has been tested in vitro against Gram-positive and Gram-negative . The tests were performed in the dark and after irradiation with visible light. The antimicrobial activity of the compound enhanced after light irradiation and was found slightly more sensitive than . The increase in antimicrobial activity after light irradiation is due to the generation of singlet oxygen particles, which attack bacterial cell membranes.
Topics: Naphthalimides; Dendrimers; Polyamines; Microbial Sensitivity Tests; Anti-Bacterial Agents; Fluorescence; Pseudomonas aeruginosa; Hydrogen-Ion Concentration; Bacillus cereus; Light; Fluorescent Dyes; Spectrometry, Fluorescence
PubMed: 38731451
DOI: 10.3390/molecules29091960 -
Nanoscale May 2024Immune activation, whether occurring from direct immune checkpoint blockade or indirectly as a result of chemotherapy, is an approach that has drastically impacted the... (Review)
Review
Immune activation, whether occurring from direct immune checkpoint blockade or indirectly as a result of chemotherapy, is an approach that has drastically impacted the way we treat cancer. Utilizing patients' own immune systems for anti-tumor efficacy has been translated to robust immunotherapies; however, clinically significant successes have been achieved in only a subset of patient populations. Dendrimers and dendritic polymers have recently emerged as a potential nanocarrier platform that significantly improves the therapeutic efficacy of current and next-generation cancer immunotherapies. In this paper, we highlight the recent progress in developing dendritic polymer-based therapeutics with immune-modulating properties. Specifically, dendrimers, dendrimer hybrids, and dendronized copolymers have demonstrated promising results and are currently in pre-clinical development. Despite their early stage of development, these nanocarriers hold immense potential to make profound impact on cancer immunotherapy and combination therapy. This overview provides insights into the potential impact of dendrimers and dendron-based polymers, offering a preview of their potential utilities for various aspects of cancer treatment.
Topics: Humans; Immunotherapy; Dendrimers; Neoplasms; Nanoparticles; Animals; Drug Carriers; Polymers
PubMed: 38727407
DOI: 10.1039/d4nr00635f -
Nanomaterials (Basel, Switzerland) May 2024A novel biomass-based magnetic nanoparticle (FeO-P-CMC/PAMAM) was synthesized by crosslinking carboxymethyl chitosan (CMC) and poly(amidoamine) (PAMAM), followed by...
A novel biomass-based magnetic nanoparticle (FeO-P-CMC/PAMAM) was synthesized by crosslinking carboxymethyl chitosan (CMC) and poly(amidoamine) (PAMAM), followed by phosphorylation with the incorporation of magnetic ferric oxide nanoparticles. The characterization results verified the successful functionalization and structural integrity of the adsorbents with a surface area of . 43 m/g. Batch adsorption experiments revealed that the adsorbent exhibited a maximum adsorption capacity of 1513.47 mg·g for U(VI) at pH 5.5 and 298.15 K, with FeO-P-CMC/G1.5-2 showing the highest affinity among the series. The adsorption kinetics adhered to a pseudo-second-order model ( = 0.99, = 463.81 mg·g, = 2.15×10 g·mg·min), indicating a chemically driven process. Thermodynamic analysis suggested that the adsorption was endothermic and spontaneous (ΔH° = 14.71 kJ·mol, ΔG° = -50.63 kJ·mol, 298. 15 K), with increasing adsorption capacity at higher temperatures. The adsorbent demonstrated significant selectivity for U(VI) in the presence of competing cations, with FeO-P-CMC/G1.5-2 showing a high selectivity coefficient. The performed desorption and reusability tests indicated that the adsorbent could be effectively regenerated using 1M HCl, maintaining its adsorption capacity after five cycles. XPS analysis highlighted the role of phosphonate and amino groups in the complexation with uranyl ions, and validated the existence of bimodal U4f peaks at 380.1 eV and 390.1 eV belonging to U 4f and U 4f. The results of this study underscore the promise of the developed adsorbent as an effective and selective material for the treatment of uranium-contaminated wastewater.
PubMed: 38727404
DOI: 10.3390/nano14090810 -
ADMET & DMPK 2024Treatments using antimicrobial agents have faced many difficulties as a result of biofilm formation by pathogenic microorganisms. The biofilm matrix formed by these... (Review)
Review
BACKGROUND AND PURPOSE
Treatments using antimicrobial agents have faced many difficulties as a result of biofilm formation by pathogenic microorganisms. The biofilm matrix formed by these microorganisms prevents antimicrobial agents from penetrating the interior where they can exact their activity effectively. Additionally, extracellular polymeric molecules associated with biofilm surfaces can absorb antimicrobial compounds, lowering their bioavailability. This problem has resulted in the quest for alternative treatment protocols, and the development of nanomaterials and devices through nanotechnology has recently been on the rise.
RESEARCH APPROACH
The literature on dendrimers was searched for in databases such as Google Scholar, PubMed, and ScienceDirect.
KEY RESULTS
As a nanomaterial, dendrimers have found useful applications as a drug delivery vehicle for antimicrobial agents against biofilm-mediated infections to circumvent these defense mechanisms. The distinctive properties of dendrimers, such as multi-valency, biocompatibility, high water solubility, non-immunogenicity, and biofilm matrix-/cell membrane fusogenicity (ability to merge with intracellular membrane or other proteins), significantly increase the efficacy of antimicrobial agents and reduce the likelihood of recurring infections.
CONCLUSION
This review outlines the current state of dendrimer carriers for biofilm treatments, provides examples of their real-world uses, and examines potential drawbacks.
PubMed: 38720923
DOI: 10.5599/admet.1917 -
Analytica Chimica Acta Jun 2024MicroRNAs, as oncogenes or tumor suppressors, enable to up or down-regulate gene expression during tumorigenesis. The detection of miRNAs with high sensitivity is...
BACKGROUND
MicroRNAs, as oncogenes or tumor suppressors, enable to up or down-regulate gene expression during tumorigenesis. The detection of miRNAs with high sensitivity is crucial for the early diagnosis of cancer. Inspired by biological ion channels, artificial nanochannels are considered as an excellent biosensing platform with relatively high sensitivity and stability. The current nanochannel biosensors are mainly based on homogeneous membranes, and their monotonous structure and functionality limit its further development. Therefore, it is necessary to develop a heterostructured nanochannel with high ionic current rectification to achieve highly sensitive miRNA detection.
RESULTS
In this work, an asymmetric heterostructured nanochannel constructed from dendrimer-gold nanoparticles network and anodic aluminum oxide are designed through an interfacial super-assembly method, which can regulate ion transport and achieve sensitive detection of target miRNA. The symmetry breaking is demonstrated to endow the heterostructured nanochannels with an outstanding ionic current rectification performance. Arising from the change of surface charges in the nanochannels triggered by DNA cascade signal amplification in solution, the proposed heterogeneous nanochannels exhibits excellent DNA-regulated ionic current response. Relying on the nucleic acid's hybridization and configuration transformation, the target miRNA-122 associated with liver cancer can be indirectly quantified with a detection limit of 1 fM and a wide dynamic range from 1 fM to 10 pM. The correlation fitting coefficient R2 of the calibration curve can reach to 0.996. The experimental results show that the method has a good recovery rate (98%-105 %) in synthetic samples.
SIGNIFICANCE
This study reveals how the surface charge density of nanochannels regulate the ionic current response in the heterostructured nanochannels. The designed heterogeneous nanochannels not only possess high ionic current rectification property, but also enable to induce superior transport performance by the variation of surface chemistry. The proposed biosensor is promising for applications in early diagnosis of cancers, life science research, and single-entity electrochemical detection.
Topics: MicroRNAs; Gold; Dendrimers; Aluminum Oxide; Humans; Biosensing Techniques; Metal Nanoparticles; Limit of Detection; Electrochemical Techniques; Nanostructures
PubMed: 38719407
DOI: 10.1016/j.aca.2024.342630 -
Journal of Colloid and Interface Science Sep 2024By combination of dendritic topological structures with photopolymerizable diacetylene, here we report on supramolecular chiral assembly of the dendronized diacetylenes...
By combination of dendritic topological structures with photopolymerizable diacetylene, here we report on supramolecular chiral assembly of the dendronized diacetylenes in water. These dendronized diacetylenes are constituted with three-fold dendritic oligoethylene glycols (OEGs), bridged with a dipeptide from phenylalanine and glycine. These dendronized amphiphiles exhibit intensive propensity to aggregate in water and form helical fibers, which show characteristic thermoresponsive behavior with phase transition temperatures dominated by hydrophilicity of the dendritic OEGs. Topochemical polymerization of these supramolecular fibers through UV irradiation transfers them into the covalent helical dendronized polydiacetylenes. Chirality of these dendronized polydiacetylenes can be mediated through the thermally-induced phase transitions, but is also intriguingly dependent on vortex via stirring. Through stirring the solutions, chiralities of the dendronized polydiacetylenes are inverted, which can be reversibly recovered after keeping still the solution. Hydrogels are formed from these dendronized diacetylenes through concentration-enhanced interactions between the supramolecular fibers. Their mechanical properties can be greatly increased through thermally-enhanced interactions between the fibers with storage moduli increased from 20 Pa to a few hundred Pa. In addition, through photo-polymerization, the supramolecular fibers are transferred into covalent dendronized polydiacetylenes, and the corresponding hydrogels show much improved mechanical properties with storage moduli about 10 kPa.
PubMed: 38718585
DOI: 10.1016/j.jcis.2024.05.016 -
Current Pharmaceutical Biotechnology Apr 2024Cancer remains a significant global health challenge, necessitating innovative approaches to enhance the efficacy and specificity of therapeutic interventions while...
Cancer remains a significant global health challenge, necessitating innovative approaches to enhance the efficacy and specificity of therapeutic interventions while minimizing adverse effects on healthy tissues. Nanotechnology has emerged as a promising avenue in cancer treatment, offering novel strategies for targeted drug delivery. Nanoparticles, liposomes, and polymer-based systems have played pivotal roles in revolutionizing cancer therapy. Nanotechnology possesses unique physicochemical properties, enabling efficient encapsulation of therapeutic agents and controlled and prolonged release at tumour sites. Advancement in formulations using nanotechnology has made it possible to make multifunctional systems that respond to the microenvironment of a tumour by releasing payloads in response to changes in pH, temperature, or enzymes. Stimuli-responsive polymers can release drugs in response to external cues, enabling site-specific drug release and minimizing systemic exposure. This review explores recent studies and preclinical trials that show how nanoparticles, liposomes, and polymerbased systems could be used to treat cancer, discussing challenges such as scalability, regulatory approval, and potential toxicity concerns along with patents published recently.
PubMed: 38716551
DOI: 10.2174/0113892010279483240417050548