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International Journal of Nanomedicine 2024This review article discusses the potential of nanomaterials in targeted therapy and immunomodulation for stroke-induced immunosuppression. Although nanomaterials have... (Review)
Review
This review article discusses the potential of nanomaterials in targeted therapy and immunomodulation for stroke-induced immunosuppression. Although nanomaterials have been extensively studied in various biomedical applications, their specific use in studying and addressing immunosuppression after stroke remains limited. Stroke-induced neuroinflammation is characterized by T-cell-mediated immunodepression, which leads to increased morbidity and mortality. Key observations related to immunodepression after stroke, including lymphopenia, T-cell dysfunction, regulatory T-cell imbalance, and cytokine dysregulation, are discussed. Nanomaterials, such as liposomes, micelles, polymeric nanoparticles, and dendrimers, offer advantages in the precise delivery of drugs to T cells, enabling enhanced targeting and controlled release of immunomodulatory agents. These nanomaterials have the potential to modulate T-cell function, promote neuroregeneration, and restore immune responses, providing new avenues for stroke treatment. However, challenges related to biocompatibility, stability, scalability, and clinical translation need to be addressed. Future research efforts should focus on comprehensive studies to validate the efficacy and safety of nanomaterial-based interventions targeting T cells in stroke-induced immunosuppression. Collaborative interdisciplinary approaches are necessary to advance the field and translate these innovative strategies into clinical practice, ultimately improving stroke outcomes and patient care.
Topics: Animals; Humans; Cytokines; Nanomedicine; Nanoparticles; Nanostructures; Stroke; T-Lymphocytes
PubMed: 38882535
DOI: 10.2147/IJN.S456632 -
ACS Omega Jun 2024Dendrimers are employed as functional elements in contrast agents and are proposed as nontoxic vehicles for drug delivery. Toxicity is a property that is to be evaluated...
Dendrimers are employed as functional elements in contrast agents and are proposed as nontoxic vehicles for drug delivery. Toxicity is a property that is to be evaluated for this novel class of bionanomaterials for in vivo applications. The current research is hampered due to the lack of structured data sets for toxicity studies for dendrimers. In this work, we have built a data set by curating literature for toxicity data and augmented it with structural and physicochemical features. We present a comprehensive, feature-rich database of dendrimer toxicity measured across various cell lines for prediction, design, and optimization studies. We have also explored novel computational approaches for predicting dendrimer cytotoxicity. We demonstrate superior outcomes for toxicity prediction using essential regression in the space of small data sets.
PubMed: 38882163
DOI: 10.1021/acsomega.4c01775 -
Chemical Science Jun 2024The light-intensity dependence of multi-photon absorption (MPA) affords outstanding spatial control. Furthermore, compared to the higher-energy photons needed for...
The light-intensity dependence of multi-photon absorption (MPA) affords outstanding spatial control. Furthermore, compared to the higher-energy photons needed for analogous linear absorption, the lower-energy photons involved in MPA often correspond to important wavelengths, such as those of the biological and telecommunications "windows". It is therefore of crucial importance to develop molecules that exhibit outstanding MPA cross-sections. However, although progress has been made with two-photon absorption, there is currently a dearth of efficient instantaneous -photon absorbers ( > 2), a key reason being the scarcity of structure-property studies required to understand higher-order MPA. We herein report systematically-varied metallodendrimers up to third-generation in size, together with their nonlinear absorptive responses over the spectral range 600-2520 nm. We show that the dendrimers exhibit exceptional instantaneous three- to six-photon absorption cross-sections, with maximal values increasing with dendrimer generation and installation of solubilizing group, and we report that changing the groups at the dendrimer periphery can shift the wavelengths of the PA maxima. We also describe time-dependent DFT studies that have facilitated assignment of the key linear and nonlinear transitions and disclosed the crucial role of the metal in the outstanding MPA performance.
PubMed: 38873073
DOI: 10.1039/d4sc01127a -
Vaccine: X Aug 2024Scorpion envenoming (SE) is a public health problem in developing countries. In Algeria, the population exposed to the risk of SE was estimated at 86.45% in 2019. Thus,...
Scorpion envenoming (SE) is a public health problem in developing countries. In Algeria, the population exposed to the risk of SE was estimated at 86.45% in 2019. Thus, the development of a vaccine to protect the exposed population against scorpion toxins would be a major advance in the fight against this disease. This work aimed to evaluate the immunoprotective effect of a Multiple Antigenic Peptide against the Aah II toxin of scorpion, the most dangerous scorpion species in Algeria. The immunogen MAP1Aah2 was designed and tested accordingly. This molecule contains a B epitope, derived from Aah II toxin, linked by a spacer to a universal T epitope, derived from the tetanus toxin. The results showed that MAP1Aah2 was non-toxic despite the fact that its sequence was derived from Aah II toxin. The immunoenzymatic assay revealed that the 3 immunization regimens tested generated specific anti-MAP1Aah2 antibodies and cross-reacted with the toxin. Mice immunized with this immunogen were partially protected against mortality caused by challenge doses of 2 and 3 LD of the toxin. The survival rate and developed symptoms varied depending on the adjuvant and the challenge dose used. In the neutralization test, the immune sera of mice having received the immunogen with incomplete Freund's adjuvant neutralized a challenge dose of 2 LD50. Hence, the concept of using peptide dendrimers, based on linear epitopes of scorpion toxins, as immunogens against the parent toxin was established. However, the protective properties of the tested immunogen require further optimizations.
PubMed: 38868522
DOI: 10.1016/j.jvacx.2024.100503 -
Proceedings of the National Academy of... Jun 2024Fluorine magnetic resonance imaging (F-MRI) is particularly promising for biomedical applications owing to the absence of fluorine in most biological systems. However,...
Fluorine magnetic resonance imaging (F-MRI) is particularly promising for biomedical applications owing to the absence of fluorine in most biological systems. However, its use has been limited by the lack of safe and water-soluble imaging agents with high fluorine contents and suitable relaxation properties. We report innovative F-MRI agents based on supramolecular dendrimers self-assembled by an amphiphilic dendrimer composed of a hydrophobic alkyl chain and a hydrophilic dendron. Specifically, this amphiphilic dendrimer bears multiple negatively charged terminals with high fluorine content, which effectively prevented intra- and intermolecular aggregation of fluorinated entities via electrostatic repulsion. This permitted high fluorine nuclei mobility alongside good water solubility with favorable relaxation properties for use in F-MRI. Importantly, the self-assembling F-MRI agent was able to encapsulate the near-infrared fluorescence (NIRF) agent DiR and the anticancer drug paclitaxel for multimodal F-MRI and NIRF imaging of and theranostics for pancreatic cancer, a deadly disease for which there remains no adequate early detection method or efficacious treatment. The F-MRI and multimodal F-MRI and NIRF imaging studies on human pancreatic cancer xenografts in mice confirmed the capability of both imaging modalities to specifically image the tumors and demonstrated the efficacy of the theranostic agent in cancer treatment, largely outperforming the clinical anticancer drug paclitaxel. Consequently, these dendrimer nanosystems constitute promising F-MRI agents for effective cancer management. This study offers a broad avenue to the construction of F-MRI agents and theranostics, exploiting self-assembling supramolecular dendrimer chemistry.
Topics: Dendrimers; Animals; Theranostic Nanomedicine; Humans; Mice; Fluorine; Paclitaxel; Magnetic Resonance Imaging; Cell Line, Tumor; Pancreatic Neoplasms; Fluorine-19 Magnetic Resonance Imaging; Mice, Nude; Contrast Media
PubMed: 38865273
DOI: 10.1073/pnas.2322403121 -
Journal of the American Chemical Society Jun 2024Antibiotic-resistant pathogens have been declared by the WHO as one of the major public health threats facing humanity. For that reason, there is an urgent need for...
Antibiotic-resistant pathogens have been declared by the WHO as one of the major public health threats facing humanity. For that reason, there is an urgent need for materials with inherent antibacterial activity able to replace the use of antibiotics, and in this context, hydrogels have emerged as a promising strategy. Herein, we introduce the next generation of cationic hydrogels with antibacterial activity and high versatility that can be cured on demand in less than 20 s using thiol-ene click chemistry (TEC) in aqueous conditions. The approach capitalizes on a two-component system: (i) telechelic polyester-based dendritic-linear-dendritic (DLDs) block copolymers of different generations heterofunctionalized with allyl and ammonium groups, as well as (ii) polyethylene glycol (PEG) cross-linkers functionalized with thiol groups. These hydrogels resulted in highly tunable materials where the antibacterial performance can be adjusted by modifying the cross-linking density. Off-stoichiometric hydrogels showed narrow antibacterial activity directed toward Gram-negative bacteria. The presence of pending allyls opens up many possibilities for functionalization with biologically interesting molecules. As a proof-of-concept, hydrophilic cysteamine hydrochloride as well as N-hexyl-4-mercaptobutanamide, as an example of a thiol with a hydrophobic alkyl chain, generated three-component networks. In the case of cysteamine derivatives, a broader antibacterial activity was noted than the two-component networks, inhibiting the growth of Gram-positive bacteria. Additionally, these systems presented high versatility, with storage modulus values ranging from 270 to 7024 Pa and different stability profiles ranging from 1 to 56 days in swelling experiments. Good biocompatibility toward skin cells as well as strong adhesion to multiple surfaces place these hydrogels as interesting alternatives to conventional antibiotics.
Topics: Anti-Bacterial Agents; Hydrogels; Dendrimers; Microbial Sensitivity Tests; Adhesives; Polyethylene Glycols; Polymers; Humans; Molecular Structure; Click Chemistry
PubMed: 38865148
DOI: 10.1021/jacs.4c03673 -
Current Gene Therapy Jun 2024Acetylresveratrol (AC-Res), to date, is a powerful stilbene phytoalexin generated organically or as a component of a plant's defensive system, is a significant plant...
BACKGROUND
Acetylresveratrol (AC-Res), to date, is a powerful stilbene phytoalexin generated organically or as a component of a plant's defensive system, is a significant plant phenolic chemical portion and is investigated as a therapy option for a number of disorders. Owing to its inadequate stabilisation and considerable conformation rigidity, the utility of AC-Res as a medication is limited.
OBJECTIVE
The current review article outlined the structure of AC-Res, their methods of activity, and the latest technological progress in the administration of these molecules. It is conceivable to deduce that AC-Res has a variety of consequences for the cellular functions of infected cells.
METHODS
The literature survey for the present article was gathered from the authentic data published by various peer-reviewed publishers employing Google Scholar and PubMedprioritizing Scopus and Web of Science indexed journals as the search platform focusing on AC-Res pharmacological actions, particularly in the English language.
RESULT
Despite its extensive spectrum of biological and therapeutic applications, AC-Res has become a source of increasing concern. Depending on the researchers, AC-Res possesses radioprotective, cardioprotective, neurological, anti-inflammatory, and anti-microbial potential. It also has anti-cancer and antioxidant properties.
CONCLUSION
To avoid non-specific cytotoxicity, optimization efforts are presently emphasizing the possible usage of AC-Res based on nanocrystals, nanoparticles and dendrimers, and nanocrystals. Finally, while using AC-Res in biology is still a way off, researchers agree that if they continue to explore it, AC-Res and similar parts will be recognized as actual possibilities for a variety of things in the next years.
PubMed: 38860906
DOI: 10.2174/0115665232291487240603093218 -
Advances in Clinical and Experimental... Jun 2024This review examines recent progress in developing nanoscale drug delivery systems for biomedical applications. Key nanocarriers, including inorganic nanoparticles,... (Review)
Review
This review examines recent progress in developing nanoscale drug delivery systems for biomedical applications. Key nanocarriers, including inorganic nanoparticles, dendrimers, protein nanoparticles, polymeric micelles, liposomes, carbon nanotubes (CNTs), quantum dots (QDs), and biopolymeric nanoparticles, were summarized. Compared with free drugs, the tunable physicochemical properties of these materials allow for the encapsulation of therapeutics and improved pharmacokinetics. However, limitations such as toxicity, poor biodegradability, lack of controlled release, and low encapsulation efficiency remain. Inorganic nanoparticles exhibit issues with accumulation and toxicity. Dendrimers require complex syntheses and demonstrations of long-term safety. Protein nanoparticles suffer from low drug loading and stability. Polymeric micelles have stability and tumor penetration limitations. Liposomes exhibit low encapsulation efficiency and rapid clearance. Carbon nanotubes demonstrate toxicity and poor aqueous solubility. Quantum dots contain heavy metals, leading to toxicity. Biopolymeric nanoparticles have low stability and control over release kinetics. Strategies such as surface engineering with polymers and ligands aim to enhance nanoparticle targeting and biocompatibility. The combination of nanostructures in hybrid systems aims to synergize benefits while mitigating individual limitations. Stimulus-responsive and multifunctional nanoparticles enable triggered release and imaging capabilities. Overall, continued research into novel bioinspired designs, smart responsiveness and hybrid approaches is critical to fully realize the clinical potential of engineered nanomedicines for advanced drug delivery applications.
PubMed: 38860712
DOI: 10.17219/acem/186846 -
Journal of Biomedical Materials... Jun 2024Protein biotherapeutics typically require expensive cold-chain storage to maintain their fold and function. Packaging proteins in the dry state via lyophilization can...
Protein biotherapeutics typically require expensive cold-chain storage to maintain their fold and function. Packaging proteins in the dry state via lyophilization can reduce these cold-chain requirements. However, formulating proteins for lyophilization often requires extensive optimization of excipients that both maintain the protein folded state during freezing and drying (i.e., "cryoprotection" and "lyoprotection"), and form a cake to carry the dehydrated protein. Here we show that sweet corn phytoglycogens, which are glucose dendrimers, can act as both a protein lyoprotectant and a cake-forming agent. Phytoglycogen (PG) dendrimers from 16 different maize sources (PG1-16) were extracted via ethanol precipitation. PG size was generally consistent at ~70-100 nm for all variants, whereas the colloidal stability in water, protein contaminant level, and maximum density of cytocompatibility varied for PG1-16. 10 mg/mL PG1, 2, 9, 13, 15, and 16 maintained the activity of various proteins, including green fluorescent protein, lysozyme, β-galactosidase, and horseradish peroxidase, over a broad range of concentrations, through multiple rounds of lyophilization. PG13 was identified as the lead excipient candidate as it demonstrated narrow dispersity, colloidal stability in phosphate-buffered saline, low protein contaminants, and cytocompatibility up to 10 mg/mL in NIH3T3 cell cultures. All dry protein-PG13 mixtures had a cake-like appearance and all frozen protein-PG13 mixtures had a T' of ~ -26°C. The lyoprotection and cake-forming properties of PG13 were density-dependent, requiring a minimum density of 5 mg/mL for maximum activity. Collectively these data establish PG dendrimers as a new class of excipient to formulate proteins in the dry state.
PubMed: 38856491
DOI: 10.1002/jbm.a.37761 -
Theranostics 2024The availability of non-invasive drug delivery systems capable of efficiently transporting bioactive molecules across the blood-brain barrier to specific cells at the...
The availability of non-invasive drug delivery systems capable of efficiently transporting bioactive molecules across the blood-brain barrier to specific cells at the injury site in the brain is currently limited. Delivering drugs to neurons presents an even more formidable challenge due to their lower numbers and less phagocytic nature compared to other brain cells. Additionally, the diverse types of neurons, each performing specific functions, necessitate precise targeting of those implicated in the disease. Moreover, the complex synthetic design of drug delivery systems often hinders their clinical translation. The production of nanomaterials at an industrial scale with high reproducibility and purity is particularly challenging. However, overcoming this challenge is possible by designing nanomaterials through a straightforward, facile, and easily reproducible synthetic process. In this study, we have developed a third-generation 2-deoxy-glucose functionalized mixed layer dendrimer () utilizing biocompatible and cost-effective materials a highly facile convergent approach, employing copper-catalyzed click chemistry. We further evaluated the systemic neuronal targeting and biodistribution of , and brain delivery of a neuroprotective agent pioglitazone () in a pediatric traumatic brain injury (TBI) model. The exhibits favorable characteristics including high water solubility, biocompatibility, biological stability, nanoscale size, and a substantial number of end groups suitable for drug conjugation. Upon systemic administration in a pediatric mouse model of traumatic brain injury (TBI), the localizes in neurons at the injured brain site, clears rapidly from off-target locations, effectively delivers , ameliorates neuroinflammation, and improves behavioral outcomes. The promising results coupled with a convenient synthetic approach for the construction of makes it a potential nanoplatform for addressing brain diseases.
Topics: Animals; Dendrimers; Neurons; Drug Delivery Systems; Deoxyglucose; Neuroprotective Agents; Mice; Pioglitazone; Blood-Brain Barrier; Brain Injuries, Traumatic; Brain; Brain Diseases; Humans; Disease Models, Animal; Tissue Distribution; Male
PubMed: 38855177
DOI: 10.7150/thno.95476