استكشف المجموعة الواسعة من العناوين المتاحة.

Enhancing the robustness of functional biomacromolecules is a critical challenge in biotechnology, which if addressed would enhance their use in pharmaceuticals, chemical processing and biostorage. Here we report a novel method, inspired by natural biomineralization processes, which provides unprecedented protection of biomacromolecules by encapsulating them within a class of porous materials termed metal-organic frameworks. We show that proteins, enzymes and DNA rapidly induce the formation of protective metal-organic framework coatings under physiological conditions by concentrating the framework building blocks and facilitating crystallization around the biomacromolecules. The resulting biocomposite is stable under conditions that would normally decompose many biological macromolecules. For example, urease and horseradish peroxidase protected within a metal-organic framework shell are found to retain bioactivity after being treated at 80 °C and boiled in dimethylformamide (153 °C), respectively. This rapid, low-cost biomimetic mineralization process gives rise to new possibilities for the exploitation of biomacromolecules.

Air filtration has become an essential need for passive pollution control. However, most of the commercial air purifiers rely on dense fibrous filters, which have good particulate matter (PM) removal capability but poor biocidal effect. Here we present the photocatalytic bactericidal properties of a series of metal-organic frameworks (MOFs) and their potentials in air pollution control and personal protection. Specifically, a zinc-imidazolate MOF (ZIF-8) exhibits almost complete inactivation of Escherichia coli (E. coli) (>99.9999% inactivation efficiency) in saline within 2 h of simulated solar irradiation. Mechanistic studies indicate that photoelectrons trapped at Zn centers within ZIF-8 via ligand to metal charge transfer (LMCT) are responsible for oxygen-reduction related reactive oxygen species (ROS) production, which is the dominant disinfection mechanism. Air filters fabricated from ZIF-8 show remarkable performance for integrated pollution control, with >99.99% photocatalytic killing efficiency against airborne bacteria in 30 min and 97% PM removal. This work may shed light on designing new porous solids with photocatalytic antibiotic capability for public health protection.

Intratumoral immunotherapy is an emerging modality for the treatment of solid tumors. Toll-like receptor (TLR) agonists have shown promise for eliciting immune responses, but systemic administration often results in the development of adverse side effects. Herein, we investigate whether localized delivery of the TLR agonist, resiquimod (R848), via platelet membrane-coated nanoparticles (PNP-R848) elicits antitumor responses. The membrane coating provides a means of enhancing interactions with the tumor microenvironment, thereby maximizing the activity of R848. Intratumoral administration of PNP-R848 strongly enhances local immune activation and leads to complete tumor regression in a colorectal tumor model, while providing protection against repeated tumor re-challenges. Moreover, treatment of an aggressive breast cancer model with intratumoral PNP-R848 delays tumor growth and inhibits lung metastasis. Our findings highlight the promise of locally delivering immunostimulatory payloads using biomimetic nanocarriers, which possess advantages such as enhanced biocompatibility and natural targeting affinities.

Imidazole was first synthesized by Heinrich Debus in 1858 and was obtained by the reaction of glyoxal and formaldehyde in ammonia, initially called glyoxaline. The current literature provides much information about the synthesis, functionalization, physicochemical characteristics and biological role of imidazole. Imidazole is a structure that, despite being small, has a unique chemical complexity. It is a nucleus that is very practical and versatile in its construction/functionalization and can be considered a rich source of chemical diversity. Imidazole acts in extremely important processes for the maintenance of living organisms, such as catalysis in enzymatic processes. Imidazole-based compounds with antibacterial, anti-inflammatory, antidiabetic, antiparasitic, antituberculosis, antifungal, antioxidant, antitumor, antimalarial, anticancer, antidepressant and many others make up the therapeutic arsenal and new bioactive compounds proposed in the most diverse works. The interest and importance of imidazole-containing analogs in the field of medicinal chemistry is remarkable, and the understanding from the development of the first blockbuster drug cimetidine explores all the chemical and biological concepts of imidazole in the context of research and development of new drugs.

Immunochemotherapy combines a chemotherapeutic agent with an immune-modulating agent and represents an attractive approach to improve cancer therapy. However, the success of immunochemotherapy is hampered by the lack of a strategy to effectively co-deliver the two therapeutics to the tumours. Here we report the development of a dual-functional, immunostimulatory nanomicellar carrier that is based on a prodrug conjugate of PEG with NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor currently used for reversing tumour immune suppression. An Fmoc group, an effective drug-interactive motif, is also introduced into the carrier to improve the drug loading capacity and formulation stability. We show that PEG -Fmoc-NLG alone is effective in enhancing T-cell immune responses and exhibits significant antitumour activity in vivo. More importantly, systemic delivery of paclitaxel (PTX) using the PEG -Fmoc-NLG nanocarrier leads to a significantly improved antitumour response in both breast cancer and melanoma mouse models.

Microporous metal-organic frameworks (MOFs) that display permanent porosity show great promise for a myriad of purposes. The potential applications of MOFs can be developed further and extended by encapsulating various functional species (for example, nanoparticles) within the frameworks. However, despite increasing numbers of reports of nanoparticle/MOF composites, simultaneously to control the size, composition, dispersed nature, spatial distribution and confinement of the incorporated nanoparticles within MOF matrices remains a significant challenge. Here, we report a controlled encapsulation strategy that enables surfactant-capped nanostructured objects of various sizes, shapes and compositions to be enshrouded by a zeolitic imidazolate framework (ZIF-8). The incorporated nanoparticles are well dispersed and fully confined within the ZIF-8 crystals. This strategy also allows the controlled incorporation of multiple nanoparticles within each ZIF-8 crystallite. The as-prepared nanoparticle/ZIF-8 composites exhibit active (catalytic, magnetic and optical) properties that derive from the nanoparticles as well as molecular sieving and orientation effects that originate from the framework material.

In this work, we have successfully synthesized a bimetallic (Zinc and Cobalt) Zeolitic Imidazolate Framework (Zn Co -ZIF), a class in a wider microporous Metal-Organic Framework (MOF) family. The synthesized nanostructures maintain both water stability like ZIF-8 (solely Zn containing) and charge transfer electronic band in the visible optical spectrum as ZIF-67 (solely Co containing). Crystal structure from XRD, high resolution transmission electron microscopy (HRTEM) followed by elemental mapping (EDAX) confirm structural stability and omnipresence of the metal atoms (Zn and Co) across the nanomaterial with equal proportion. Existence of charge transfer state consistent with ZIF67 and intact ultrafast excited state dynamics of the imidazolate moiety in both ZIF-8 and ZIF-67, is evidenced from steady state and time resolved optical spectroscopy. The thermal and aqueous stabilities of Zn Co -ZIF are found to be better than ZIF-67 but comparable to ZIF-8 as evidenced by solubility, scanning electron microscopy (SEM) and XRD studies of the material in water. We have evaluated the photoinduced ROS generation by the mixed ZIF employing dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. We have also explored the potentiality of the synthesized material for the alternate remediation of methicillin resistant Staphylococcus aureus (MRSA) infection through the photoinduced reactive oxygen species (ROS) generation and methylene blue (MB) degradation kinetics.

5′-Adenosine monophosphate–activated protein kinase (AMPK) is a master regulator of energy homeostasis in eukaryotes. Despite three decades of investigation, the biological roles of AMPK and its potential as a drug target remain incompletely understood, largely because of a lack of optimized pharmacological tools. We developed MK-8722, a potent, direct, allosteric activator of all 12 mammalian AMPK complexes. In rodents and rhesus monkeys, MK-8722–mediated AMPK activation in skeletal muscle induced robust, durable, insulin-independent glucose uptake and glycogen synthesis, with resultant improvements in glycemia and no evidence of hypoglycemia. These effects translated across species, including diabetic rhesus monkeys, but manifested with concomitant cardiac hypertrophy and increased cardiac glycogen without apparent functional sequelae.

Tumour-associated macrophages are abundant in many cancers, and often display an immune-suppressive M2-like phenotype that fosters tumour growth and promotes resistance to therapy. Yet, macrophages are highly plastic and can also acquire an anti-tumorigenic M1-like phenotype. Here, we show that R848, an agonist of the toll-like receptors TLR7 and TLR8 identified in a morphometric-based screen, is a potent driver of the M1 phenotype in vitro and that R848-loaded β-cyclodextrin nanoparticles (CDNP-R848) lead to efficient drug delivery to tumour-associated macrophages in vivo. As a monotherapy, the administration of CDNP-R848 in multiple tumour models in mice altered the functional orientation of the tumour immune microenvironment towards an M1 phenotype, leading to controlled tumour growth and protecting the animals against tumour rechallenge. When used in combination with the immune checkpoint inhibitor anti-PD-1, we observed improved immunotherapy response rates, including in a tumour model resistant to anti-PD-1 therapy alone. Our findings demonstrate the ability of rationally engineered drug-nanoparticle combinations to efficiently modulate tumour-associated macrophages for cancer immunotherapy.

The use of lower concentrations and fewer applications of herbicides is one of the prime objectives of the sustainable agriculture as it decreases the toxicity to non-targeted organisms and the risk of wider environmental contamination. In the present work, nanoparticles were developed for encapsulation of the herbicides imazapic and imazapyr. Alginate/chitosan and chitosan/tripolyphosphate nanoparticles were manufactured, and their physicochemical stability was evaluated. Determinations were made of the encapsulation efficiency and release kinetics, and the toxicity of the nanoparticles was evaluated using cytotoxicity and genotoxicity assays. The effects of herbicides and herbicide-loaded nanoparticles on soil microorganisms were studied in detail using real-time polymerase chain reactions. The nanoparticles showed an average size of 400 nm and remained stable during 30 days of storage at ambient temperature. Satisfactory encapsulation efficiencies of between 50 and 70% were achieved for both types of particles. Cytotoxicity assays showed that the encapsulated herbicides were less toxic, compared to the free compounds, and genotoxicity was decreased. Analyses of soil microbiota revealed changes in the bacteria of the soils exposed to the different treatments. Our study proves that encapsulation of the herbicides improved their mode of action and reduced their toxicity, indicating their suitability for use in future practical applications.