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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 -
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 -
Alzheimer's Research & Therapy May 2024In Alzheimer's disease (AD), microglia surround extracellular plaques and mount a sustained inflammatory response, contributing to the pathogenesis of the disease....
BACKGROUND
In Alzheimer's disease (AD), microglia surround extracellular plaques and mount a sustained inflammatory response, contributing to the pathogenesis of the disease. Identifying approaches to specifically target plaque-associated microglia (PAMs) without interfering in the homeostatic functions of non-plaque associated microglia would afford a powerful tool and potential therapeutic avenue.
METHODS
Here, we demonstrated that a systemically administered nanomedicine, hydroxyl dendrimers (HDs), can cross the blood brain barrier and are preferentially taken up by PAMs in a mouse model of AD. As proof of principle, to demonstrate biological effects in PAM function, we treated the 5xFAD mouse model of amyloidosis for 4 weeks via systemic administration (ip, 2x weekly) of HDs conjugated to a colony stimulating factor-1 receptor (CSF1R) inhibitor (D-45113).
RESULTS
Treatment resulted in significant reductions in amyloid-beta (Aβ) and a stark reduction in the number of microglia and microglia-plaque association in the subiculum and somatosensory cortex, as well as a downregulation in microglial, inflammatory, and synaptic gene expression compared to vehicle treated 5xFAD mice.
CONCLUSIONS
This study demonstrates that systemic administration of a dendranib may be utilized to target and modulate PAMs.
Topics: Animals; Alzheimer Disease; Microglia; Dendrimers; Plaque, Amyloid; Mice, Transgenic; Disease Models, Animal; Mice; Amyloid beta-Peptides; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Humans
PubMed: 38711159
DOI: 10.1186/s13195-024-01470-3 -
International Journal of Pharmaceutics Jun 2024Ocular delivery is the most challenging aspect in the field of pharmaceutical research. The major hurdle for the controlled delivery of drugs to the eye includes the... (Review)
Review
Ocular delivery is the most challenging aspect in the field of pharmaceutical research. The major hurdle for the controlled delivery of drugs to the eye includes the physiological static barriers such as the complex layers of the cornea, sclera and retina which restrict the drug from permeating into the anterior and posterior segments of the eye. Recent years have witnessed inventions in the field of conventional and nanocarrier drug delivery which have shown considerable enhancement in delivering small to large molecules across the eye. The dynamic challenges associated with conventional systems include limited drug contact time and inadequate ocular bioavailability resulting from solution drainage, tear turnover, and dilution or lacrimation. To this end, various bioactive-based nanosized carriers including liposomes, ethosomes, niosomes, dendrimer, nanogel, nanofibers, contact lenses, nanoprobes, selenium nanobells, nanosponge, polymeric micelles, silver nanoparticles, and gold nanoparticles among others have been developed to circumvent the limitations associated with the conventional dosage forms. These nanocarriers have been shown to achieve enhanced drug permeation or retention and prolong drug release in the ocular tissue due to their better tissue adherence. The surface charge and the size of nanocarriers (10-1000 nm) are the important key factors to overcome ocular barriers. Various nanocarriers have been shown to deliver active therapeutic molecules including timolol maleate, ampicillin, natamycin, voriconazole, cyclosporine A, dexamethasone, moxifloxacin, and fluconazole among others for the treatment of anterior and posterior eye diseases. Taken together, in a nutshell, this extensive review provides a comprehensive perspective on the numerous facets of ocular drug delivery with a special focus on bioactive nanocarrier-based approaches, including the difficulties and constraints involved in the fabrication of nanocarriers. This also provides the detailed invention, applications, biodistribution and safety-toxicity of nanocarriers-based therapeutcis for the ophthalmic delivery.
Topics: Humans; Animals; Drug Carriers; Administration, Ophthalmic; Eye; Drug Delivery Systems; Nanoparticles; Eye Diseases; Nanoparticle Drug Delivery System; Biological Availability; Drug Liberation
PubMed: 38703931
DOI: 10.1016/j.ijpharm.2024.124192 -
EJNMMI Radiopharmacy and Chemistry May 2024Radiation nanomedicines are nanoparticles labeled with radionuclides that emit α- or β-particles or Auger electrons for cancer treatment. We describe here our... (Review)
Review
BACKGROUND
Radiation nanomedicines are nanoparticles labeled with radionuclides that emit α- or β-particles or Auger electrons for cancer treatment. We describe here our 15 years scientific journey studying locally-administered radiation nanomedicines for cancer treatment. We further present a view of the radiation nanomedicine landscape by reviewing research reported by other groups.
MAIN BODY
Gold nanoparticles were studied initially for radiosensitization of breast cancer to X-radiation therapy. These nanoparticles were labeled with In to assess their biodistribution after intratumoural vs. intravenous injection. Intravenous injection was limited by high liver and spleen uptake and low tumour uptake, while intratumoural injection provided high tumour uptake but low normal tissue uptake. Further, [In]In-labeled gold nanoparticles modified with trastuzumab and injected iintratumourally exhibited strong tumour growth inhibition in mice with subcutaneous HER2-positive human breast cancer xenografts. In subsequent studies, strong tumour growth inhibition in mice was achieved without normal tissue toxicity in mice with human breast cancer xenografts injected intratumourally with gold nanoparticles labeled with β-particle emitting Lu and modified with panitumumab or trastuzumab to specifically bind EGFR or HER2, respectively. A nanoparticle depot (nanodepot) was designed to incorporate and deliver radiolabeled gold nanoparticles to tumours using brachytherapy needle insertion techniques. Treatment of mice with s.c. 4T1 murine mammary carcinoma tumours with a nanodepot incorporating [Y]Y-labeled gold nanoparticles inserted into one tumour arrested tumour growth and caused an abscopal growth-inhibitory effect on a distant second tumour. Convection-enhanced delivery of [Lu]Lu-AuNPs to orthotopic human glioblastoma multiforme (GBM) tumours in mice arrested tumour growth without normal tissue toxicity. Other groups have explored radiation nanomedicines for cancer treatment in preclinical animal tumour xenograft models using gold nanoparticles, liposomes, block copolymer micelles, dendrimers, carbon nanotubes, cellulose nanocrystals or iron oxide nanoparticles. These nanoparticles were labeled with radionuclides emitting Auger electrons (In, Tc, I, Pd, Pt, Pt), β-particles (Lu, Re, Re, Y, Au, I) or α-particles (Ac, Bi, Pb, At, Ra). These studies employed intravenous or intratumoural injection or convection enhanced delivery. Local administration of these radiation nanomedicines was most effective and minimized normal tissue toxicity.
CONCLUSIONS
Radiation nanomedicines have shown great promise for treating cancer in preclinical studies. Local intratumoural administration avoids sequestration by the liver and spleen and is most effective for treating tumours, while minimizing normal tissue toxicity.
PubMed: 38703297
DOI: 10.1186/s41181-024-00266-y -
Frontiers in Bioengineering and... 2024With a prevalence of 12.5% of all new cancer cases annually, breast cancer stands as the most common form of cancer worldwide. The current therapies utilized for breast...
With a prevalence of 12.5% of all new cancer cases annually, breast cancer stands as the most common form of cancer worldwide. The current therapies utilized for breast cancer are constrained and ineffective in addressing the condition. siRNA-based gene silencing is a promising method for treating breast cancer. We have developed an aptamer-conjugated dendritic multilayered nanoconjugate to treat breast cancer. Initially, we transformed the hydroxyl groups of the hyperbranched bis-MPA polyester dendrimer into carboxylic groups. Subsequently, we linked these carboxylic groups to tetraethylenepentamine to form a positively charged dendrimer. In addition, the mucin-1 (MUC1) aptamer was attached to the dendrimer using a heterobifunctional polyethylene glycol. Characterizing dendrimers involved H NMR and dynamic light scattering techniques at every production stage. A gel retardation experiment was conducted to evaluate the successful binding of siRNA with targeted and non-targeted dendrimers. The targeted dendrimers exhibited no harmful effects on the NIH-3T3 fibroblast cells and RBCs, indicating their biocompatible characteristics. Confocal microscopy demonstrated significant higher uptake of targeted dendrimers than non-targeted dendrimers in MCF-7 breast cancer cells. The real-time PCR results demonstrated that the targeted dendrimers exhibited the most pronounced inhibition of the target gene expression compared to the non-targeted dendrimers and lipofectamine-2000. The caspase activation study confirmed the functional effect of survivin silencing by dendrimer, which led to the induction of apoptosis in breast cancer cells. The findings indicated that Mucin-1 targeted hyperbranched bis-MPA polyester dendrimer carrying siRNA could successfully suppress the expression of the target gene in breast cancer cells.
PubMed: 38699430
DOI: 10.3389/fbioe.2024.1383495 -
Bioactive Materials Aug 2024Effective treatment of Parkinson's disease (PD), a prevalent central neurodegenerative disorder particularly affecting the elderly population, still remains a huge...
Effective treatment of Parkinson's disease (PD), a prevalent central neurodegenerative disorder particularly affecting the elderly population, still remains a huge challenge. We present here a novel nanomedicine formulation based on bioactive hydroxyl-terminated phosphorous dendrimers (termed as AK123) complexed with fibronectin (FN) with anti-inflammatory and antioxidative activities. The created optimized AK123/FN nanocomplexes (NCs) with a size of 223 nm display good colloidal stability in aqueous solution and can be specifically taken up by microglia through FN-mediated targeting. We show that the AK123/FN NCs are able to consume excessive reactive oxygen species, promote microglia M2 polarization and inhibit the nuclear factor-kappa B signaling pathway to downregulate inflammatory factors. With the abundant dendrimer surface hydroxyl terminal groups, the developed NCs are able to cross blood-brain barrier (BBB) to exert targeted therapy of a PD mouse model through the AK123-mediated anti-inflammation for M2 polarization of microglia and FN-mediated antioxidant and anti-inflammatory effects, thus reducing the aggregation of α-synuclein and restoring the contents of dopamine and tyrosine hydroxylase to normal levels . The developed dendrimer/FN NCs combine the advantages of BBB-crossing hydroxyl-terminated bioactive phosphorus dendrimers and FN, which is expected to be extended for the treatment of different neurodegenerative diseases.
PubMed: 38699237
DOI: 10.1016/j.bioactmat.2024.04.005 -
Cell Death Discovery May 2024Allergic airway inflammation (AAI), including allergic rhinitis (AR) and allergic asthma, is driven by epithelial barrier dysfunction and type 2 inflammation. However,...
Allergic airway inflammation (AAI), including allergic rhinitis (AR) and allergic asthma, is driven by epithelial barrier dysfunction and type 2 inflammation. However, the underlying mechanism remains uncertain and available treatments are constrained. Consequently, we aim to explore the role of cell-free DNA (cfDNA) in AAI and assess the potential alleviating effects of cationic polymers (CPs) through cfDNA elimination. Levels of cfDNA were evaluated in AR patients, allergen-stimulated human bronchial epithelium (BEAS-2B cells) and primary human nasal epithelium from both AR and healthy control (HC), and AAI murine model. Polyamidoamine dendrimers-generation 3 (PAMAM-G3), a classic type of cationic polymers, were applied to investigate whether the clearance of cfDNA could ameliorate airway epithelial dysfunction and inhibit AAI. The levels of cfDNA in the plasma and nasal secretion from AR were higher than those from HC (P < 0.05). Additionally, cfDNA levels in the exhaled breath condensate (EBC) were positively correlated with Interleukin (IL)-5 levels in EBC (R = 0.4191, P = 0.0001). Plasma cfDNA levels negatively correlated with the duration of allergen immunotherapy treatment (R = -0.4297, P = 0.006). Allergen stimulated cfDNA secretion in vitro (P < 0.001) and in vivo (P < 0.0001), which could be effectively scavenged with PAMAM-G3. The application of PAMAM-G3 inhibited epithelial barrier dysfunction in vitro and attenuated the development of AAI in vivo. This study elucidates that cfDNA, a promising biomarker for monitoring disease severity, aggravates AAI and the application of intranasal PAMAM-G3 could potentially be a novel therapeutic intervention for AAI. Allergen stimulates the secretion of cell-free DNA (cfDNA) in both human and mouse airway. Intranasal polyamidoamine dendrimers-generation 3 (PAMAM-G3) scavenges cfDNA and alleviates allergic airway inflammation.
PubMed: 38698016
DOI: 10.1038/s41420-024-01980-x -
Heliyon May 2024Hybrid nanostructures exhibit a synergistic combination of features derived from their individual components, showcasing novel characteristics resulting from their... (Review)
Review
Hybrid nanostructures exhibit a synergistic combination of features derived from their individual components, showcasing novel characteristics resulting from their distinctive structure and chemical/physical properties. Surface modifiers play a pivotal role in shaping INPs' primary attributes, influencing their physicochemical properties, stability, and functional applications. Among these modifiers, dendrimers have gained attention as highly effective multifunctional agents for INPs, owing to their unique structural qualities, dendritic effects, and physicochemical properties. Dendrimers can be seamlessly integrated with diverse inorganic nanostructures, including metal NPs, carbon nanostructures, silica NPs, and QDs. Two viable approaches to achieving this integration involve either growing or grafting dendrimers, resulting in inorganic nanostructure-cored dendrimers. The initial step involves functionalizing the nanostructures' surface, followed by the generation of dendrimers through stepwise growth or attachment of pre-synthesized dendrimer branches. This hybridization imparts superior qualities to the resulting structure, including biocompatibility, solubility, high cargo loading capacity, and substantial functionalization potential. Combining the unique properties of dendrimers with those of the inorganic nanostructure cores creates a multifunctional system suitable for diverse applications such as theranostics, bio-sensing, component isolation, chemotherapy, and cargo-carrying applications. This review summarizes the recent developments, with a specific focus on the last five years, within the realm of dendrimers. It delves into their role as modifiers of INPs and explores the potential applications of INP-cored dendrimers in the biomedical applications.
PubMed: 38694058
DOI: 10.1016/j.heliyon.2024.e29726