Selective Release Research Articles

Preparation of PEG/ZIF-8@HF drug delivery system for melanoma treatment via oral administration

Melanoma is one of the highly malignant tumors whose incidence and fatality rates have been increased year by year. However, in addition to early surgical resection, there still lacks specific targeted drugs and treatment strategies. In this study, it was discovered that hinokiflavone (HF) encapsulated in zeolitic imidazolate framework-8 (ZIF-8) exhibited a superior anti-melanoma effect in vitro and in vivo. HF was encapsulated in ZIF-8 through a one-step synthesis method, and polyethylene glycol (PEG-2000) was used to optimize the size and dispersion of the drug-loaded complex (PEG/ZIF-8@HF). The results show that the prepared PEG/ZIF-8@HF has a high encapsulation efficiency (92.12%) and can achieve selective drug release in an acidic microenvironment. The results of in vitro anti-melanoma experiments indicate that PEG/ZIF-8@HF shows up-regulation of reactive oxygen species (ROS) levels and can restrain the migration and invasion of B16F10 cells. Moreover, in vivo animal experiments further confirm that PEG/ZIF-8@HF shows anti-tumor effect by up-regulating the pro-apoptotic proteins caspase-3 and caspase-8, and down-regulating the migration-promoting invasion protein MMP-9. This study developed a safe and effective oral administration of HF based on the high-efficiency delivery ZIF-8 system, which provides an effective treatment strategy for melanoma.

Selective Anticancer Therapy Based on a HA-CD44 Interaction Inhibitor Loaded on Polymeric Nanoparticles.

Hyaluronic acid (HA), through its interactions with the cluster of differentiation 44 (CD44), acts as a potent modulator of the tumor microenvironment, creating a wide range of extracellular stimuli for tumor growth, angiogenesis, invasion, and metastasis. An innovative antitumor treatment strategy based on the development of a nanodevice for selective release of an inhibitor of the HA-CD44 interaction is presented. Computational analysis was performed to evaluate the interaction of the designed tetrahydroisoquinoline-ketone derivative (JE22) with CD44 binding site. Cell viability, efficiency, and selectivity of drug release under acidic conditions together with CD44 binding capacity, effect on cell migration, and apoptotic activity were successfully evaluated. Remarkably, the conjugation of this CD44 inhibitor to the nanodevice generated a reduction of the dosis required to achieve a significant therapeutic effect.

Three narrative patterns of the city image visually presented on Instagram under the influence of self-presentation

The emerging trend of online self-presentation that cause the selective release of photos and thus create biased city images circulating in social networks deserves greater research attention. As a response to this, the paper investigates the image of Wangfujing Beijing on Instagram, which cements its reputation as a symbol of traditional food culture but limits its potential to be the embodiment of cosmopolitan urban living. After arguing that the exotic images of the food market can better help Instagrammers play an urban adventurer before followers, the paper analyzes over 5500 sets of Instagram data, and then examines three narrative patterns used to describe the place, corresponding to the context description, the connection establishment, and the visual emphasis of the dominant theme. The visual storytelling techniques used in them will assist in understanding the image-based communication between social network users and thereby increase the possibility of managing the online city image.

Photosensitized co-generation of nitric oxide and singlet oxygen Enhanced toxicity against ovarian cancer cells.

Near micromolar concentrations of nitric oxide (NO) induce tumor cells death. However, an appropriate NO load has to be delivered selectively to the tumor site in order to avoid NO loss and secondary NO-induced effects. The encapsulation of millimolar concentrations of a NO source and an appropriate trigger of NO release within phospatidylcholine-based liposomes should provide an efficient tool for the selective release of the needed NO payload. In this work we report the photosensitized generation of singlet oxygen and NO from folate-targeted PEGylated liposomes, containing AlPcS4 as the sensitizer and S-nitrosoglutathione (GSNO), in millimolar amounts, as the NO source. Amounts of singlet oxygen detected outside the liposome when using PEGylated liposomes are near 200 % larger when GSNO is present inside the liposomes as compared to its absence. These liposomes, conjugated to folate, were found to enhance the photosensitized cytotoxicity to A2780CP20 ovarian cancer cells as compared to liposomes containing the sensitizer but no GSNO (30 % as compared to 70 % cell viability) under the conditions of this work. Fluorescense of AlPcS4 was observed inside cells incubated with folate-conjugated liposomes but not with liposomes without folate. The photosensitized activity enhancement by GSNO increased when light fluence or liposome concentration were increased. The majority of ovarian cancer patients are initially diagnosed with disseminated intra-abdominal disease (stages III-IV) and have a 5-year survival of less than 20%. This work suggests a novel ovarian cancer nodules treatment via the use of tumor-targeted liposome nanoparticles with the capability of generating simultaneously reactive oxygen and nitrogen species upon illumination with near-infrared light.

3D printed tablets containing oxaliplatin loaded alginate nanoparticles for colon cancer targeted delivery. An in vitro/in vivo study.

This study aimed to develop a colon-targeted tablet of oxaliplatin (OP) using the combination of nanotechnology and fused deposition modeling (FDM) 3D printing to improve its antitumor activity, tumor targetability, and safety profile. Eudragit L100-55 filament containing OP loaded alginate nanoparticles (OP-NPs) were fabricated using hot-melt extrusion method and printed by an FDM printer to 3D printed tablets with good uniformity in the drug content and selective release of OP in the colonic environment. The antitumor effect of 3D printed tablets containing OP-NPs in CT-26 tumor-bearing mice was evaluated compared to intravenous and oral administration of OP solution, and compressed tablets containing OP-NPs, which were prepared by direct compression method with the same formulation. The antitumor effect of 3D printed tablets containing OP-NPs was remarkable and comparable with intravenous OP solution (p˃0.05) with a better safety profile, whereas compressed tablets did not show any significant antitumor effect, probably in terms of non-selective drug release in stomach and upper intestine environments. This study highlights the potential of the combination of nanotechnology and 3D printing in the preparation of colon-specific drug delivery systems of chemotherapeutic drugs with good antitumor activity, tumor targetability, and safety profile for colorectal cancer treatment.

Perspectives in Adsorptive and Catalytic Mitigations of NOx Using Metal–Organic Frameworks

Because of its high polluting effect, a growing research interest in NOx monitoring, removal, and control has been noticed in the last years. Motivated by the high degree of functional and structural tunability of metal–organic frameworks (MOFs), researchers explored potential MOF-based adsorbents, sensors, and catalysts for NOx mitigation/control. However, this area of research is still in its infancy. In addition, the physical–chemical properties of NOx make this task extremely challenging as some materials suffer relatively weak thermal and/or chemical stability. Nevertheless, some recent encouraging studies have demonstrated superior stability properties that enable MOFs to be considered as alternative benchmark materials for the capture and conversion of NOx. This review offers an overview on the recent progress made in this field and provides some interesting routes on the uses of MOFs for selective NOx adsorption, release, and/or catalytic conversion (via selective catalytic reduction or photocatalysis).

A microenvironment-responsive FePt probes for imaging-guided Fenton-enhanced radiotherapy of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) continues to be one of the most fatal malignancies with increasing morbidity, and potent therapeutics are urgently required given its insensitivity to traditional treatments. Here, we have developed a microenvironment-responsive FePt probes for the highly efficient Fenton-enhanced radiotherapy (FERT) of HCC. The selective release of Fe2+ in the acidic tumor microenvironment, but not in normal tissue, together with enhanced levels of hydrogen peroxide produced through the Pt radiosensitization effect, facilitates the generation of an enormous amount of hydroxyl radicals through the Fenton reaction, thereby extending the radiotherapeutic cascade and realizing a powerful therapeutic efficacy for HCC. Moreover, the “burst” release of Fe2+ contributes to the T2-to-T1 magnetic resonance imaging (MRI) switching effect, which informs the release of Fe2+, making imaging-guided cancer therapy feasible. This work not only breaks the bottleneck of traditional radiotherapy for HCC while minimally affecting normal tissues, but also provides a new strategy for FERT imaging guidance.Graphical

Application of Nanotechnology in Insect Pest Management: A Review

Insect pests are one of the most concerned biotic obstacles in agriculture and humans are constantly in search of new strategies to control them. Chemical pesticides are extensively used for controlling insect pests which cause a lot of problem, such as pest resistance, elimination of natural enemies, environmental pollution, loss of biodiversity and human health hazards. As an alternative pest control strategy, the application of nanotechnology in insect pest management can be one of the most promising ways to overcome the problems related to the application of conventional chemical pesticide. According to various research findings, the nano based materials are described as very effective in insect pest management because they have larger surface area which ensures the contact of more volume of pesticides with the insect pests. They also provide selective, targeted and long term-controlled release of formulation of nanomaterial which is ecologically more viable. Moreover, the required amount of nano-insecticide is also very small for controlling insect and thus the pesticide load in the environment gets reduced. So, use of nanotechnology for insect pest management is considered as environmentally sustainable and a brilliant insect control strategy in green agriculture. SAARC J. Agric., 19(2): 1-11 (2021)

Arthroscopic Evaluation of LUCL Stability After Selective Release and Repair of the Lateral Collateral Ulnar Ligament

To perform a selective release and repair of the LUCL of the elbow and arthroscopic assessment of postoperative stability.

ATP-Responsive Liposomes via Screening of Lipid Switches Designed to Undergo Conformational Changes upon Binding Phosphorylated Metabolites.

Liposomal delivery vehicles can dramatically enhance drug transport. However, their clinical application requires enhanced control over content release at diseased sites. For this reason, triggered release strategies have been explored, although a limited toolbox of stimuli has thus far been developed. Here, we report a novel strategy for stimuli-responsive liposomes that release encapsulated contents in the presence of phosphorylated small molecules. Our formulation efforts culminated in selective cargo release driven by ATP, a universal energy source that is upregulated in diseases such as cancer. Specifically, we developed lipid switches 1a-b bearing two ZnDPA units designed to undergo substantial conformational changes upon ATP binding, thereby disrupting membrane packing and triggering the release of encapsulated contents. Dye leakage assays using the hydrophobic dye Nile red validated that ATP-driven release was selective over 11 similar phosphorylated metabolites, and release of the hydrophilic dye calcein was also achieved. Multiple alternative lipid switch structures were synthesized and studied (1c-d and 2), which provided insights into the structural features that render 1a-b selective toward ATP-driven release. Importantly, analysis of cellular delivery using fluorescence microscopy in conjunction with pharmacological ATP manipulation showed that liposome delivery was specific, as it increased upon intracellular ATP accumulation, and was inhibited by ATP downregulation. Our new approach shows strong prospects for enhancing the selectivity of release and payload delivery to diseased cells driven by metabolites such as ATP, providing an exciting new paradigm for controlled release.

Multifunctional nanoparticles recruiting hyaluronic acid ligand and polyplexes containing low molecular weight protamine and ATP-Sensitive DNA motif for doxorubicin delivery

Nanoparticles (NPs) that combine stimuli-triggered drug release and active targeting of tumors signify a dual smart strategy in chemotherapeutic inhibition of cancer growth. Recently, low molecular weight protamine (PrtLMW) has been utilized to replace its precursor protamine (Prt) in the clinic, as it exhibits less undesirable side effects. In this study, we compared the merits of using Prt and PrtLMW to assemble two NPs. Anticancer drug doxorubicin (Dox) was loaded into ATP-binding aptamer (AptATP), a DNA sequence that undergoes a conformational change when exposed to an Adenosine-5′-triphosphate (ATP) rich environment. Dox-AptATP then complexed with the positively charged Prt or PrtLMW, and the resulting cationic, condensed core was further coated with high molecular weight hyaluronic acid (HAHMW), a known ligand for tumor marker CD44. The resulting two NPs were characterized then inspected for selective uptake and release in CD44 overexpressing breast cancer cells (MDA-MB-231) using flow cytometry. The localization of the released Dox in the cytosol and nuclei of the cells was confirmed by confocal microscopy. A dose-dependent cytotoxic effect was observed by performing MTT assay. Annexin-V FITC apoptosis assay showed that the NPs were able to induce apoptosis efficiently. The replacement of Prt with PrtLMW proved to be beneficial in increasing the release rate of Dox, and it exhibited a substantially increased cytotoxic effect on the treated cancer cells.

Application of Pulsed Electric Fields and High-Pressure Homogenization in Biorefinery Cascade of C. vulgaris Microalgae.

In this study, a cascaded cell disintegration process, based on pulsed electric fields (PEF - 20 kV/cm, 100 kJ/kgSUSP.) and high-pressure homogenization (HPH - 150 MPa, 5 passes) was designed for the efficient and selective release of intracellular compounds (water-soluble proteins, carbohydrates, and lipids) from C. vulgaris suspensions during extraction in water (25 °C, 1 h) and ethyl acetate (25 °C, 3 h). Recovery yields of target compounds from cascaded treatments (PEF + HPH) were compared with those observed when applying PEF and HPH treatments individually. Particle size distribution and scanning electron microscopy analyses showed that PEF treatment alone did not induce any measurable effect on cell shape/structure, whereas HPH caused complete cell fragmentation and debris formation, with an undifferentiated release of intracellular matter. Spectra measurements demonstrated that, in comparison with HPH alone, cascaded treatments increased the selectivity of extraction and improved the yields of carbohydrates and lipids, while higher yields of water-soluble proteins were measured for HPH alone. This work, therefore, demonstrates the feasibility of sequentially applying PEF and HPH treatments in the biorefinery of microalgae, projecting a beneficial impact in terms of process economics due to the potential reduction of the energy requirements for separation/purification stages.

Microenvironment-responsive chemotherapeutic nanogels for enhancing tumor therapy via DNA damage and glutathione consumption

Although targeted therapy and immunotherapy are now shining in the treatment of some cancers, chemotherapy is still the cornerstone of drug treatment for many cancer patients. The emergence of chemotherapy prodrugs can improve the drug activity and reduce the side effects of chemotherapy. When used, the tumor microenvironment has characteristics different from normal tissues, and the existence of the microenvironment provided a more convenient way to design responsive nanodrugs. Herein, we designed a glutathione (GSH)-responsive prodrug nanogels for enhancing tumor chemotherapy. In the nanogels of HHNP, 10-hydroxycamptothecin (HCPT) played an essential role in killing cancer cells. HCPT was jointed with a cross-linker agent with disulfide bond and was further coated with polyethylene glycol, which not only prolonged the half-life of the drug, but also made HCPT accurate transport to the tumor fractions and achieved precise and controllable release. The proposal of HHNP effectively retained the biological activity of the drug, and introduced functions such as targeting, selective release and biodegradation, which greatly improved the medical efficiency of the drug and effectively reduced the toxic and side effects. This chemotherapeutic prodrug nanogel offers a new window for constructing efficient drug delivery platform.

ROS-Sensitive Polymer Micelles for Selective Degradation in Primary Human Monocytes from Patients with Active IBD.

Inflammatory bowel disease (IBD) is characterized by increased levels of reactive oxygen species (ROS) in inflamed areas of the gastrointestinal tract and in circulating immune cells, providing novel opportunities for targeted drug delivery. In the recent experiments, oxidation-responsive polymeric nanostructures selectively degrade in the presence of H2 O2 . Based on these results, it is hypothesized that such degradation process can be triggered in a similar way by the incubation with stimulated monocytes isolated from patients with IBD. A first indication is given by a significant correlation between excessive ROS and degradation of micelles in monocytes isolated from healthy individuals after phorbol 12-myristate 13-acetate (PMA) stimulation. But even if the ROS-sensitive micelles are incubated with nonstimulated monocytes from patients with active IBD, a spontaneous degradation is observed in contrast to micelles incubated with monocytes from healthy donors. The findings indicate that the thioether-based micelles are indeed promising for selective drug release in the presence of activated immune cells.

Catalytic Amidomethylative [2+2+2] Cycloaddition of Formaldimine and Styrenes toward N-Heterocycles

AbstractChemo-switchable catalytic [2+2+2] cycloaddition of alkenes with formaldimines is reported. Bis(tosylamido)methane (BTM) and 1,2-ditosyl-1,2-diazetidine (DTD), two bench-stable precursors for highly reactive tosylformaldimine, have been identified to be effective. BTM worked as a selective releaser of the formaldimine for catalytic [2+2+2] reactions toward hexahydropyrimidine products via a presumable ‘imine–alkene–imine’ addition. A unique catalytic retro-[2+2] reaction of DTD was used and has enabled a proposed ‘imine–alkene–alkene’ pathway with high chemoselectivity for the synthesis of 2,4-di­arylpiperidine derivatives. The two alternative processes are catalyzed by the simple and environmentally benign catalysts InCl3 and FeBr2, respectively.

Layer-resolved release of epitaxial layers in III-V heterostructure via a buffer-free mechanical separation technique.

Layer-release techniques for producing freestanding III-V epitaxial layers have been actively developed for heterointegration of single-crystalline compound semiconductors with Si platforms. However, for the release of target epitaxial layers from III-V heterostructures, it is required to embed a mechanically or chemically weak sacrificial buffer beneath the target layers. This requirement severely limits the scope of processable materials and their epi-structures and makes the growth and layer-release process complicated. Here, we report that epitaxial layers in commonly used III-V heterostructures can be precisely released with an atomic-scale surface flatness via a buffer-free separation technique. This result shows that heteroepitaxial interfaces of a normal lattice-matched III-V heterostructure can be mechanically separated without a sacrificial buffer and the target interface for separation can be selectively determined by adjusting process conditions. This technique of selective release of epitaxial layers in III-V heterostructures will provide high fabrication flexibility in compound semiconductor technology.

Selective electrochemical capture and release of uranyl from aqueous alkali, lanthanide, and actinide mixtures using redox-switchable carboranes.

We report the selective electrochemical biphasic capture of the uranyl cation (UO22+) from mixed-metal alkali (Cs+), lanthanide (Nd3+, Sm3+), and actinide (Th4+, UO22+) aqueous solutions to an organic, 1,2-dichloroethane (DCE), phase using the ortho-substituted nido-carborane anion, [1,2-(Ph2PO)2-1,2-C2B10H10]2− (POCb2−). The reduced POCb2− is generated by electrochemical reduction of the closo-carborane, POCb, prior to mixing with the aqueous mixed-metal solution. Subsequent UO22+ release from the captured product, [UO2(POCb)2]2−, was performed by galvanostatic bulk electrolysis of the DCE phase and back-extraction of UO22+ to a fresh aqueous phase. The selective capture and release of UO22+ was confirmed by combined ICP-OES and NMR spectral analyses of the aqueous and organic phases, respectively, against the newly synthesized nido-carborane complexes, [[CoCp*2][Cs(POCb)]]2, [CoCp*2]3[Nd(POCb)3], [CoCp*2]3[Sm(POCb)3], and [CoCp*2]2[Th(POCb)3].

Towards lager beer aroma improvement via selective amino acid release by proteases during mashing

Higher alcohols and esters are key compounds from fermentation that help define the character of beer. Higher alcohols are mainly produced by yeast via the Ehrlich amino acid degradation pathway of especially leucine, isoleucine, valine, and phenylalanine. Augmenting the concentration of these amino acids can enhance the output of the Ehrlich pathway. Unlike previous studies, the work reported here explores the possibility of combining endo- and exo-proteases to selectively release these amino acids to potentially impact on flavour formation. The wort from enzyme treated mash was fermented by Saccharomyces pastorianus and the green beer was analysed by GC/MS. Treatment with proteases in laboratory scale mashing increased the level of leucine, isoleucine, valine, and phenylalanine by up to twofold. Fermentation of the wort, produced about 10% more isoamyl alcohol and 17% more isoamyl acetate derived from leucine, compared to the control. © 2022 Novozymes AS. Journal of the Institute of Brewing published by John Wiley & Sons Ltd on behalf of The Institute of Brewing & Distilling.

Development of Camptothecin Nano-Prodrugs Based on Trimethyl Lock Groups Toward Selective Drug Release in Cancer Cells

Development of Camptothecin Nano-Prodrugs Based on Trimethyl Lock Groups Toward Selective Drug Release in Cancer Cells

Hydrogen sulphide-triggered theranostic prodrugs based on the dynamic chemistry of tetrazines.

Dynamic nucleophilic aromatic substitution of tetrazines (SNTz) has been employed to build theranostic prodrugs that are activated by hydrogen sulfide. H2S is typically found in high concentrations in some kinds of cancer cells and it is able to trigger the disassembly of tetrazine prodrugs. In such a way, a dual release of drugs and/or fluorescent compounds can be selectively triggered.