A light-controlled multi-step drug release nanosystem targeting tumor hypoxia for synergistic cancer therapy

Hypoxia is a major obstacle for cancer therapy due to its association with cell proliferation, tumor distant metastasis, and treatment resistance. In this study, a hypoxia-activated bifunctional prodrug (CC5) was designed, synthesized and encapsulated by a photo-responsive ruthenium complex-derived polymer to yield a light-controlled multi-step drug release system (CC5-RuCa) for synergistic therapy against tumor hypoxia. Under NIR irradiation, CC5-RuCa not only generated ROS to kill the cancer cells in the exterior of the tumor but also released the prodrug CC5 with enhanced intratumoral penetration in the severe hypoxia region inside the tumor tissue. In vivo studies on MDA-MB-231 xenograft models revealed that CC5-RuCa with preferential accumulation in the tumor exhibited highly efficient tumor regression through the synergistic effect of photodynamic therapy and hypoxia-activated chemotherapy.

A photo-responsive ruthenium complex-derived micelle (CC5-RuCa) loaded with CC5 was prepared for light and tumor microenvironment-controlled multistage drug-release.     

Divergent strategy for the synthesis of bottlebrush polymers via postpolymerization modification of macromonomer

A simple and divergent synthetic strategy of bottlebrush polymers (BBPs) is presented, consisting of postpolymerization modification of a macromonomer and grafting-through polymerization. Beginning with a single macromonomer, its direct modification could build a library of macromonomers with an identical chain length, thus guaranteeing the precision in the synthesis of BBPs. In this study, a newly designed norbornenyl-terminated poly(methyl acrylate) (NB-PMA) is proposed as a chemically robust template. Ti-mediated transesterification of NB-PMA successfully produces structurally diverse polyacrylates while maintaining the terminal norbornenyl group intact. All macromonomers obtained from transesterification possess a good grafting-through ring-opening metathesis polymerization reactivity, furnishing homo, random, and block BBPs in a controllable manner. Moreover, atomic force microscopy analysis supports the controlled side-chain length distribution in the resulting BBPs.     

Precursor synthesis strategy for polycyclic aromatic conjugated polymers on the application of supercapacitors

Polycyclic aromatics (PCAs) possess excellent photoelectric properties, but the construction of such compounds has been a quite challenging subject of study, mainly due to very low solubility. Herein we report a precursor synthesis strategy for polycyclic aromatic conjugated polymers. A soluble precursor polymer, that containing fusible “double U-shaped aromatic” (DUA) and perylenetetracarboxydiimide (PDI) units, was firstly synthesized by Suzuki coupling. The stereo aromatic units in polymer backbone were found to be converted into polycyclic aromatic units, i.e. hexa-peri-hexabenzocoronene (HBC), by chemical or electrochemical oxidation, which resulted in a formation of insoluble polycyclic aromatic conjugated polymers. The electrochemical oxidations that occurred at the interface of electrode and solution exhibited higher cyclization reactivity and leads to the formation of high quality films on the electrode surface. Characterization by Raman and UV-visible (UV-Vis) spectroscopy validated the successful formation of this HBC structure. Some potential applications of such thin films are being explored, and here we focus on the characteristics of supercapacitors based on their excellent electrochemical properties.     

Copper-thioguanine metallodrug with self-reinforcing circular catalysis for activatable MRI imaging and amplifying specificity of cancer therapy

For chemotherapy, drug delivery systems often suffer from the inefficient drug loading capability, which usually cause systems toxicity and extra burden to excrete carrier itself. Moreover, the cancer therapeutic efficacy is also greatly limited by the specificity of tumor microenvironment for reactive oxygen species(ROS) based cancer therapeutic strategy(e.g., chemodynamic therapy). Herein, we have developed metal-drug coordination nanoplatform that can not only be responsive to tumor microenvironment but also modulate it, so as to achieve efficient treatment of cancer. Excitingly, by employing small molecule drug(6-thioguanine) as ligand copper ions, we achieve a high drug loading rate(60.1%) and 100% of utilization of metal-drug coordination nanoplatform(Cu-TG). Interestingly, Cu-TG possessed high-efficiently horseradish peroxidase-like, glutathione peroxidase-like and catalase-like activity. Under the tumor microenvironment, Cu-TG exhibited the self-reinforcing circular catalysis that is able to amplify the cellular oxidative stress, inducing notable cancer cellular apoptosis. Moreover, Cu-TG could be activated with glutathione(GSH) and facilitated for GSH triggered 6-TG release, higher selective therapeutic effect toward cancer cells, and GSH activated T_1 weight-magnetic resonance imaging. Based on the above properties, Cu-TG exhibited magnetic resonance imaging(MRI) guiding, efficient and synergistic combination of chemodynamic and chemotherapy with self-reinforcing therapeutic outcomes in vivo.     

An in situ nanoparticle recombinant strategy for the enhancement of photothermal therapy

Photothermal therapy(PTT)-induced immune response has attracted much attention, however, which cannot work at full capacity. In this study, the simvastatin(SV) adjuvant is loaded into gold nanocages(AuNCs) to develop a simple drug delivery system, which can efficiently utilize the tumor-associated antigens(TAAs) for improving immune responses. AuNCs/SV-mediated PTT treatment enhances tumor cells damage and promotes the release of TAAs which are immediately captured by Au NCs/SV to form AuNCs/SV/...     

A nanoagent for concurrent therapy of breast cancer bone metastasis and cancer-induced bone pain through SLC7A11 interruption and photodynamic therapy

Bone metastasis, a life-threatening complication of advanced breast cancer, is often accompanied by debilitating pain(cancer-induced bone pain, CIBP) that severely impairs life quality and survival. The concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeutic options are limited. In this study, we construct a near-infrared light-activated nano-therapeutic system to meet this conundrum. In detail, sorafenib(SRF) and photosensitizer(chlorin e6, Ce6) are...     

Cationic polymers and aptamers mediated aggregation of gold nanoparticles for the colorimetric detection of arsenic(III) in aqueous solution

As(III) specifically interacts with an arsenic-binding aptamer to form an As(III)-aptamer complex, so that the following cationic polymer can aggregate gold nanoparticles (AuNPs) and cause a remarkable change in color, which enables the colorimetric detection of As(III) with high selectivity and a detection limit of 5.3 ppb.     

Enhancing the ROS generation ability of a rhodamine-decorated iridium(iii) complex by ligand regulation for endoplasmic reticulum-targeted photodynamic therapy

The endoplasmic reticulum (ER) is a very important organelle responsible for crucial biosynthetic, sensing, and signalling functions in eukaryotic cells. In this work, we established a strategy of ligand regulation to enhance the singlet oxygen generation capacity and subcellular organelle localization ability of a rhodamine-decorated iridium(iii) complex by variation of the cyclometallating ligand. The resulting metal complex showed outstanding reactive oxygen species generation efficiency (1.6-fold higher than that of rose bengal in CH₃CN) and highly specific ER localization ability, which demonstrated the promise of the metal-based photo-theranostic agent by simultaneously tuning the photochemical/physical and biological properties. Additionally, low dark cytotoxicity, high photostability and selective tumour cell uptake were featured by this complex to demonstrate it as a promising candidate in photodynamic therapy (PDT) applications. In vivo near infrared fluorescence (NIRF) imaging and tumour PDT were investigated and showed preferential accumulation at the tumour site and remarkable tumour growth suppression, respectively.

A design strategy for boosting the ROS generation of rhodamine-decorated cyclometallated iridium(iii) complexes by ligand regulation for endoplasmic reticulum-targeted precise photodynamic therapy.     

Facial strategy for radical species through Ag(I)-mediated oxidation of the alkyl trifluoroborates

A rapid and highly efficient method for the radical formation using potassium alkylfluoroborates as radical precursor is devised and developed which conducts under relatively mild condition using silver(I) oxide as the oxidant. The observed silver mirror phenomenon hints at the fact that Ag₂O is the real oxidant. This approach effectively overcomes the drawbacks-stringent reaction conditions and poor tolerance of a variety of functional groups.     

In silico enhancement of azo dye adsorption affinity for cellulose fibre through mechanistic interpretation under guidance of QSPR models using Monte Carlo method with index of ideality correlation

ABSTRACT

Azo dyes are a group of chemical moieties joined by azo (-N=N-) group with potential usefulness in different industrial applications. But these dyes are not devoid of hazardous consequence because of poor affinity for the fibre and discharge into the water stream. The chemical aspects of 72 azo dyes towards cellulose fibre in terms of their affinity by QSPR have been explored in the present work. We have employed two approaches, namely balance of correlation without IIC (TF₁) and balance of correlation with IIC (TF₂), to generate 16 QSAR models from 8 splits. The determination coefficient of calibration and validation set was found higher when the QSPR models were developed using the index of ideality correlation (IIC) parameter (TF₂). The model developed with TF₂ for split 3 was considered as a prominent model because the determination coefficient of the validation set was maximum (r ² = 0.9468). The applicability domain (AD) was also analysed based on ‘statistical defect’, d(A) for a SMILES attribute. The mechanistic interpretation was done by identifying the SMILES attributes responsible for the promoter of endpoint increase and promoter of endpoint decrease. These SMILES attributes were applied to design 15 new dyes with higher affinity for cellulose fibre.     

Development of a validated strategy for the determination of tryptamine in human cerebrospinal fluid in the presence of competitors using molecularly imprinted polymers

This study presents a validated strategy for the determination of tryptamine in the presence of its competitors, which involves the molecularly imprinted solid‐phase extraction combined with high‐performance liquid chromatography coupled with fluorimetric detection. Tryptamine‐imprinted microscale sorbent was produced from 4‐vinylbenzoic acid and ethylene glycol dimethacrylate in methanol by precipitation polymerization, and its imprinting factor was equal to 15.4 in static experiments or 18.6 in dynamic binding experiments. The method for tryptamine determination in the presence of serotonin and l ‐tryptophan was validated using a complex matrix of bovine serum albumin yielding the recoveries of tryptamine that ranged between 98.7 and 107.0%. Very low limits of detection and limits of quantification for tryptamine (19.9 and 60.3 nmol/L, respectively) allow the quantification of tryptamine in human cerebrospinal fluid in the presence of tryptophan and serotonin.     

A peptide-derived strategy for specifically targeting the mitochondria and ER of cancer cells: a new approach in fighting cancer

An effective anti-cancer therapy should exclusively target cancer cells and trigger in them a broad spectrum of cell death pathways that will prevent avoidance. Here, we present a new approach in cancer therapy that specifically targets the mitochondria and ER of cancer cells. We developed a peptide derived from the flexible and transmembrane domains of the human protein NAF-1/CISD2. This peptide (NAF-1^44-67) specifically permeates through the plasma membranes of human epithelial breast cancer cells, abolishes their mitochondria and ER, and triggers cell death with characteristics of apoptosis, ferroptosis and necroptosis. In vivo analysis revealed that the peptide significantly decreases tumor growth in mice carrying xenograft human tumors. Computational simulations of cancer vs. normal cell membranes reveal that the specificity of the peptide to cancer cells is due to its selective recognition of their membrane composition. NAF-1^44-67 represents a promising anti-cancer lead compound that acts via a unique mechanism.

An effective anti-cancer therapy should exclusively target cancer cells and trigger in them a broad spectrum of cell death pathways that will prevent avoidance.     

A new strategy for the chemoselective sulfonamide N-alkylation of sulfonyl ureas under neutral and mild conditions

An efficient and chemoselective sulfonamide N-alkylation of sulfonyl ureas is described. The sulfonyl urea derivatives, prepared in situ by the addition of an amine to an arylsulfonyl isocyanate, are selectively alkylated in excellent yields under neutral and mild conditions by treatment with trialkylphosphite-dimethyl acetylenedicarboxylate at ambient temperature.     

Confirmation of universality of time–humidity superposition principle for various water‐absorbable polymers through dynamic viscoelastic measurements under controlled conditions of relative humidity and temperature

Dynamic viscoelastic measurements were made for storage (E′) and loss (E″) tensile moduli of water‐absorbable polymers such as nylon‐6, nylon‐66, poly(vinyl alcohol), ethylene–vinyl alcohol copolymers, and regenerated cellulose under the control of stepwise scanned relative humidity at constant temperature by changes in the strain frequency over a wide range. Smooth master curves of log(E′) and log(E″) plotted against log(frequency) were successfully obtained for all samples. The evaluated shift factors changed with the relative humidity and could be interpreted well on the basis of a concept of free volume in the amorphous region. The free volume was affected sensitively, depending on the heat‐treatment condition and the types of polymers used. For nylon‐66 film, the dynamic viscoelastic measurements were made at different humidities and temperatures, from which one smooth master curve was obtained. This experimental result is important in realizing the similar effect of relative humidity and temperature on the expansion of free volume of the amorphous phase: the shift factor change induced by the relative humidity change of about 30% was equivalent to the shift factor change induced by the temperature change of about 30 °C. That is, the time–humidity superposition principle and the time–temperature superposition principle were applicable as equivalent contributors to the mechanical property of water‐absorbable polymers. © 2001 John Wiley & Sons, Inc. J Polym Sci Part B: Polym Phys 39: 1638–1650, 2001     

A strategy for characterizing the mixing state of immiscible aerosol components and the formation of multiphase aerosol particles through coagulation

We demonstrate that the coagulation of two aerosol droplets of different chemical composition can be studied directly through the unique combination of optical tweezers and Raman spectroscopy. Multiple optical traps can be established, allowing the manipulation of multiple aerosol droplets. Spontaneous Raman scattering allows the characterization of droplet composition and mixing state, permitting the phase segregation of immiscible components in multiphase aerosol to be investigated with spatial resolution. Stimulated Raman scattering allows the integrity of the droplet and uniformity of refractive index to be probed. The combination of these spectroscopic probes with optical tweezers is shown to yield unprecedented detail in studies of the coagulation of decane and water droplets.     

Analytical review of some relevant methods and devices for the determination of the specific volume on thermoplastic polymers under processing conditions

This article reviews some of the most representative methods and devices to measure the specific volume in polymeric materials found in literature. Each method is described and a comparison between the experimental conditions and typical injection molding processing conditions is discussed. In general, the main difficulty with specific volume measurements is determination of the temperature distribution through sample thickness, particularly when achieving typical processing conditions is intended. Therefore, the necessity of developing a new device which allows direct measurements of pressure and temperature at various positions along the sample thickness in order to calculate the cooling condition was identified.