RESUMEN
The design of multistimuli-responsive soft nanoparticles (NPs) often presents synthetic complexities and limited breadth in exploiting changes surrounding physiological environments. Nanocarriers that could collectively take advantage of several endogenous stimuli can offer a powerful tool in nanomedicine. Herein, we have capitalized on the chemical versatility of a single tertiary amine to construct miktoarm polymer-based nanocarriers that respond to dissolved CO2, varied pH, reactive oxygen species (ROS), and ROS + CO2. Curcumin (Cur), an anti-inflammatory phytopharmaceutic, was loaded into micelles, and we validated the sensitivity of the tertiary amine in tuning Cur release. An in vitro evaluation indicated that Cur encapsulation strongly suppressed its toxicity at high concentrations, significantly inhibited nigericin-induced secretion of interleukin-1ß by THP-1 macrophages, and the proportion of M2/M1 (anti-inflammatory/pro-inflammatory macrophages) was higher for Cur-loaded NPs than for free Cur. Our approach highlights the potential of a simple-by-design strategy in expanding the scope of polymeric NPs in drug delivery.
Asunto(s)
Dióxido de Carbono , Curcumina , Especies Reactivas de Oxígeno , Macrófagos , Curcumina/farmacología , Concentración de Iones de HidrógenoRESUMEN
Antibiotic resistance continues to pose significant health challenges. Considering severe limitations in the discovery and supply of new antibiotics, there is an unmet need to design alternative and more effective strategies for addressing this global issue. Use of polymeric nanoparticles with cationic shell surfaces offers a highly promising approach to coupling their inherent bactericidal action with sustained delivery of small lipophilic microbicides. We have utilized this platform for assembling multi-tasking soft core-shell nanoparticles from star polymers with the desired asymmetric arm composition. These stable nanoparticles with low critical micelle concentration imparted intrinsic antimicrobial potency due to high positive charge density in the corona, as well as the loading of active biocidal agents (such as curcumin and terbinafine) for potential dual and coadjuvant inhibition. This strategic combination allows for both immediate (direct contact) and extended (drug delivery) antibacterial activities for better therapeutic efficacy. Micellar nanoparticles with and without therapeutic cargo were highly efficient against both Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis), representative Gram-negative and Gram-positive bacteria, respectively. Interestingly, we observed bacteria- and concentration-dependent effects, in which higher concentrations of charged nanoparticles were more effective against E. coli, whereas B. subtilis was inhibited only at lower concentrations. This work highlights a valuable platform to achieve combination therapy through nanoparticles with charged coronas and delivery of potent therapeutics to overcome antimicrobial resistance.
RESUMEN
Branched star polymers offer exciting opportunities in enhancing the efficacy of nanocarriers in delivering biologically active lipophilic agents. It is demonstrated that the star polymeric architecture can be leveraged to yield soft nanoparticles of vesicular morphology with precisely located stimuli-sensitive chemical entities. Amphiphilic stars of AB2 (A = PEG, B = PCL) composition with/without oxidative stress or reduction responsive units at the core junction of A and B arms, are constructed using synthetic articulation. Fisetin, a natural flavonoid with remarkable anti-inflammatory and antioxidant properties, but of limited clinical value due to its poor aqueous solubility, is physically encapsulated into miktoarm star-derived aqueous polymersomes. Polymersomes and fisetin are evaluated separately, and in combination, in human microglia (HMC3), to show if i) polymersomes are toxic; ii) fisetin reduces the abundance of reactive oxygen species (ROS); and iii) fisetin modulates the activation of ERK1/2. These signaling molecules and pathways are implicated in inflammatory processes and cell survival. Fisetin, both incorporated and nonincorporated into polymersomes, reduces ROS and ERK1/2 phosphorylation in lipopolysaccharide-treated human microglia, normalizing excessive oxidative stress and ERK-mediated signaling.
Asunto(s)
Microglía , Polímeros de Estímulo Receptivo , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Flavonoles/farmacología , Humanos , Lipopolisacáridos/farmacología , Microglía/metabolismo , Polímeros/química , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Soft nanoparticles continue to offer a promising platform for the encapsulation and controlled delivery of poorly water-soluble drugs and help enhance their bioavailability at targeted sites. Linear amphiphilic block copolymers are the most extensively investigated in formulating delivery vehicles. However, more recently, there has been increasing interest in utilizing branched macromolecules for nanomedicine, as these have been shown to lower critical micelle concentrations, form particles of smaller dimensions, facilitate the inclusion of varied compositions and function-based entities, as well as provide prolonged and sustained release of cargo. In this review, it is aimed to discuss some of the key variables that are studied in tailoring branched architecture-based assemblies, and their influence on drug loading and delivery. By understanding structure-property relationships in these formulations, one can better design branched star polymers with suitable characteristics for efficient therapeutic interventions. The role played by polymer composition, chain architecture, crosslinking, stereocomplexation, compatibility between polymers and drugs, drug/polymer concentrations, and self-assembly methods in their performance as nanocarriers is highlighted.
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Nanopartículas , Polímeros , Portadores de Fármacos , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Micelas , Nanomedicina , Nanopartículas/uso terapéuticoRESUMEN
Electron transport across the transition-metal dichalcogenide (TMD)/metal interface plays an important role in determining the performance of TMD-based optoelectronic devices. However, the robustness of this process against structural heterogeneities remains unexplored, to the best of our knowledge. Here, we employ a combination of time-resolved photoemission electron microscopy (TR-PEEM) and atomic force microscopy to investigate the spatially resolved hot-electron-transfer dynamics at the monolayer (1L) MoS2/Au interface. A spatially heterogeneous distribution of 1L-MoS2/Au gap distances, along with the sub-80 nm spatial- and sub-60 fs temporal resolution of TR-PEEM, permits the simultaneous measurement of electron-transfer rates across a range of 1L-MoS2/Au distances. These decay exponentially as a function of distance, with an attenuation coefficient ß â¼ 0.06 ± 0.01 Å-1, comparable to molecular wires. Ab initio simulations suggest that surface plasmon-like states mediate hot-electron-transfer, hence accounting for its weak distance dependence. The weak distance dependence of the interfacial hot-electron-transfer rate indicates that this process is insensitive to distance fluctuations at the TMD/metal interface, thus motivating further exploration of optoelectronic devices based on hot carriers.
RESUMEN
This paper reports an effective method to prepare patterned polymer brushes on surfaces with tailored graft densities. High-density (concentrated), moderate-density (semidiluted), and low-density (diluted) polymer brushes were fabricated in patterned manners, offering defined three-dimensional patterned structures. This method uses a middle/near-UV (≥250 nm) lamp and needs only a short time (≤10 min) to fabricate prepatterns of the initiator, in sharp contrast to the previous high-energy lithography and time-consuming processes. The obtained patterned brush served as a molecular (protein) repellent/adsorptive interface based on a graft-density-dependent size-exclusion effect. This method is facile and accessible to wide ranges of tunable density and pattern shapes, which are attractive for extensive use.