Advances with metal oxide-based nanoparticles as MDR metastatic breast cancer therapeutics and diagnostics

Metal oxide nanoparticles have attracted increased attention due to their emerging applications in cancer detection and therapy. This study envisioned to highlight the great potential of metal oxide NPs due to their interesting properties including high payload, response to magnetic field, affluence of surface modification to overcome biological barriers, and biocompatibility. Mammogram, ultrasound, X-ray computed tomography (CT), MRI, positron emission tomography (PET), optical or fluorescence imaging are used for breast imaging. Drug-loaded metal oxide nanoparticle delivered to the breast cancer cells leads to higher drug uptake. Thus, enhanced the cytotoxicity to target cells compared to free drug. The drug loaded metal oxide nanoparticle formulations hold great promise to enhance efficacy of breast cancer therapy including multidrug resistant (MDR) and metastatic breast cancers. Various metal oxides including magnetic metal oxides and magnetosomes are of current interests to explore cancer drug delivery and diagnostic efficacy especially for metastatic breast cancer. Metal oxide-based nanocarrier formulations are promising for their usage in drug delivery and release to breast cancer cells, cancer diagnosis and their clinical translations.

Biomarker targeted therapy approaches for TNBC using metal oxide-based NPs are highly effective and promising.     

Silicon surface patterning via galvanic microcontact imprinting lithography

Surface patterning without requiring expensive facilities and complex procedures is a major scientific and technological challenge. We report a simple surface patterning strategy on a silicon wafer surface. This strategy, termed galvanic microcontact imprinting lithography (GMIL), is based on the spontaneous galvanic oxidation of silicon due to the electrically coupled silicon/gold mold with lithographically defined patterns. The galvanic induced silicon oxide pattern can be selectively removed in dilute HF solution or serve as a robust etchant resist in alkaline solution, enabling the formation of regular silicon microstructures on the silicon surface, affording an accessible, simple and cheap surface patterning method with no requirement of expensive and sophisticated instrumentation and facilities. These results may open exciting prospects for next-generation low-cost lithographic techniques.

The “ancient” galvanic effect opens up the possibility of silicon surface patterning in ordinary laboratories without expensive and sophisticated facilities.     

An efficient multicomponent synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a magnetic nanoparticle supported Lewis acidic deep eutectic solvent

A mild and highly efficient reaction for the synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a magnetically supported Lewis acidic deep eutectic solvent on magnetic nanoparticles (LADES@MNP) has been developed via one-pot multicomponent processes under solvent-free sonication. These reactions have good to excellent yields, mild conditions, and work-up simplicity. This method represents a new method for the preparation of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles. More importantly, LADES@MNP can be easily recovered by magnetic separation and reused five times without significant loss of catalytic activity.

A mild and highly efficient method for the synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a Lewis acidic deep eutectic solvent on magnetic nanoparticles (LADES@MNP).     

Enhancing cellular morphological changes and ablation of cancer cells via the interaction of drug co-loaded magnetic nanosystems in weak rotating magnetic fields

Magnetic nanoparticles have been widely used in cancer treatment for their potential magnetic functions and synergistic antitumor effect with therapeutic agents. In this work, we developed a polymeric nanosystem by co-loading the natural anticancer drug tetrandrine and superparamagnetic iron oxide nanoparticles for cancer combinatorial therapy. The nanosystem possessed regular morphology and superior magnetic properties. Under the action of external rotating permanent magnets, the nanosystem could transfer a rotational motion to damage the cellular membrane, which would result in the increased permeabilization of the cell membrane and damage to lysosomes. Hence, the specific characteristics of the magnetic nanosystem induced potent cytotoxicity and enhanced the effect of the tetrandrine-induced cell apoptosis. With further exploration, we found that this nanoplatform caused cell death via a lysosomal-mitochondrial apoptotic pathway with the upregulation of proapoptotic proteins (Cathepsin B, Smac/Diablo, Cytochrome C, and Caspase 3) and the down-regulation of antiapoptotic proteins (Bcl-2 and XIAP). These findings demonstrate that the combination therapy mediated by co-loaded magnetic nanosystems can be used for a multi-therapeutic effect against tumors in biomedical applications.

Tetrandrine and Fe₃O₄ nanoparticle co-loaded PLGA nanosystems produce rotational movement and promote tetrandrine release, causing a dual apoptotic effect to tumors.     

New advances on Au–magnetic organic hybrid core–shells in MRI,CT imaging,and drug delivery

Magnetic nanoparticles have been widely studied for various scientific and technological applications such as magnetic storage media, contrast agents for magnetic resonance imaging (MRI), biolabelling, separation of biomolecules, and magnetic-targeted drug delivery. A new strategy on Au–magnetic nano-hybrid core–shells was applied in MRI, CT imaging, and drug delivery, which has been received much attention nowadays. Herein, the designing of different magnetic core–shells with Au in MRI and cancer treatment is studied.

Magnetic nanoparticles have been studied for scientific and technological applications such as magnetic storage media, contrast agents for magnetic resonance imaging, biolabelling, separation of biomolecules, and magnetic-targeted drug delivery.     

Sign inversion in magnetic circularly polarised luminescence of fused aromatics with 1.6 T N-up/S-up Faraday geometry

Although 12 diamagnetic fused aromatics with or without substituents exhibit mirror-symmetric magnetic circularly polarised luminescence (MCPL) through N-up and S-up Faraday geometries under a magnetic field intensity of 1.6 T, their signs (single and multiple) and magnitudes depend strongly on either the aromatic structures or the peripheral positions of the substituents.

Diamagnetic fused aromatics exhibit mirror-symmetric magnetic circularly polarised luminescence (MCPL) depend on either the aromatic structures or the peripheral positions of the substituents through N-up and S-up Faraday geometries under a 1.6 T magnetic field.     

An efficient class of bis-NHC salts: applications in Pd-catalyzed reactions under mild reaction conditions

This study describes an efficient class of bis-N-heterocyclic carbene (bis-NHC) salts that can be easily made from commercially available and inexpensive starting materials. The application of these salts to Pd-catalyzed reactions is described. The palladium (Pd) catalyst generated in situ was highly effective under mild reaction conditions.

This study describes an efficient class of bis-N-heterocyclic carbene (bis-NHC) salts that can be easily made from commercially available and inexpensive starting materials.     

The influence of an external magnetic field on the dynamics of magnetite reduction with hydrogen

The kinetics of hydrogen reduction of magnetite was investigated in different magnetic fields. The magnetic moment measurements in situ were used for the control of the reaction. A strong difference in the magnetic properties of the reaction results was obtained for applied strong and weak magnetic fields. The X-ray diffraction and Mössbauer spectra of the reduced samples confirmed their different composition. The mechanism of the magnetic field effect is discussed.

The kinetics of hydrogen reduction of magnetite was investigated in different magnetic fields.     

Two decades of advances in diterpenoid alkaloids with cytotoxicity activities

The important pharmacological activities and structural complexity of diterpenoid alkaloids have long stimulated strong scientific interest; some of these naturally abundant compounds have been reported to be highly promising for treating cancer. From 2008 to 2018, the cytotoxicity activities of more than 250 diterpenoid alkaloids were tested against several cancer cell lines. This review focuses on the progress of diterpenoid alkaloids with different structures derived from Ranunculaceae plants and some of their derivatives with potential anticancer activities. Then, we discuss the application prospects and development of active diterpenoid alkaloids.

The important pharmacological activities and structural complexity of diterpenoid alkaloids have long stimulated strong scientific interest; some of these naturally abundant compounds have been reported to be highly promising for treating cancer.     

Smart magnetic nanopowder based on the manganite perovskite for local hyperthermia

For many medical applications related to diagnosis and treatment of cancer disease, hyperthermia plays an increasingly important role as a local heating method, where precise control of temperature and parameters of the working material is strongly required. Obtaining a smart material with “self-controlled” heating in a desirable temperature range is a relevant task. For this purpose, the nanopowder of manganite perovskite with super-stoichiometric manganese has been synthesized, which consists of soft spherical-like ferromagnetic nanoparticles with an average size of 65 nm and with a narrow temperature range of the magnetic phase transition at 42 °C. Based on the analysis of experimental magnetic data, a specific loss power has been calculated for both quasi-stable and relaxation hysteresis regions. It has been shown that the local heating of the cell structures to 42 °C may occur for a short time (∼1.5 min.) Upon reaching 42 °C, the heating is stopped due to transition of the nanopowder to the paramagnetic state. The obtained results demonstrate the possibility of using synthesized nanopowder as a smart magnetic nanomaterial for local hyperthermia with automatic heating stabilization in the safe range of hyperthermia without the risk of mechanical damage to cell structures.

Local heating of cancer cells up to 42 °C for a short time (∼1.5 min) by smart magnetic nanoparticles.     

A PCR-free screen-printed magnetic electrode for the detection of circular RNA from hepatocellular cancer based on a back-splice junction

Circular RNA (circRNA) has the potential to be applied to disease diagnosis and therapy. However, the currently available circRNA detection techniques are limited. This work proposes a sensitive and selective approach for circRNA detection based on gold nanoparticle-modified screen-printed magnetic electrodes (AuNPs-SPME). Magnetic beads (MBs) with capture probes based on specific back-splice junction (BSJ) sites were employed to identify and selectively isolate the target circRNA, which could be directly adsorbed onto the AuNPs-SPME. Then, the circRNA attached to the surface was detected by changes in the methylene blue redox signal. The simple and time-saving AuNPs-SPME is highly sensitive (LOD = 1.0 pM) to circCDYL, one of the biomarkers of hepatocellular cancer (HCC). The analytical performance of the method presented has also been verified in human serum samples, holding great promise for clinical diagnosis.

Functional magnetic beads with capture probes based on specific back-splice junction sites were employed to identify and selectively isolate target circRNA.     

Synthesis of highly substituted tetrahydroquinolines using ethyl cyanoacetate via aza-Michael–Michael addition

A three-component cascade reaction involving 2-alkenyl aniline, aldehydes, and ethyl cyanoacetate in the presence of DBU to synthesize highly substituted 1,2,3,4-tetrahydroquinolines is reported. The reaction proceeded through the Knoevenagel condensation of ethyl cyanoacetate with aldehydes followed by the aza-Michael–Michael addition with 2-alkenyl anilines to prepare the tetrahydroquinoline scaffolds.

A three-component cascade reaction involving 2-alkenyl aniline, aldehydes, and ethyl cyanoacetate in the presence of DBU to synthesize highly substituted 1,2,3,4-tetrahydroquinolines is reported.     

Evaluating the efficacy of the anticancer drug cetuximab by atomic force microscopy

Cetuximab is a monoclonal antibody that binds to the epidermal growth factor receptor, which is important in the growth of many cancers. However, the biophysical characteristics of cetuximab as an anti-cancer drug remain elusive. In this study, we adopted atomic force microscopy to measure the mechanical properties of cancer cells following cetuximab treatment and the biomechanical properties of cetuximab and epidermal growth factor receptor interactions. Atomic force microscopy can be implemented as a platform for further investigations that target the cellular stiffness and affinity of ligand–receptor as a therapeutic choice.

Atomic force microscopy can be implemented as a platform for further investigations that target the cellular stiffness and affinity of ligand–receptor as a therapeutic choice.     

A cobalt complex with 2,4,6-tris(di-2-pyridylamine)-1,3,5-triazine: antiferromagnetic couple governed single-molecule-magnet behaviour

One cobalt complex with distorted trigonal antiprismatic geometry was obtained using 2,4,6-tris(di-2-pyridylamine)-1,3,5-triazine (dipyatriz) as the ligand. X-ray crystallography showed the complex possessing a pair of metal centers, had an antiferromagnetic coupling between two Co(ii) ions. Further studied showed a field-induced slow relaxation under H_dc = 0.8 kOe. The peak of out-of-phase was observed after 1000 Hz, which exhibited a moderate slow-relaxation behaviour comparing to the magnetic couple for single Co(ii) complex. This study may provide some strategies on designing new functional molecular magnetic materials with distinct magnetic properties and diverse the structures.

One cobalt complex with distorted trigonal antiprismatic geometry was obtained using 2,4,6-tris(di-2-pyridylamine)-1,3,5-triazine (dipyatriz) as the ligand.     

Innovative application of magnetically modified bovine horn as a natural keratin resource in the role of value-added organocatalyst

This study presents the conversion of bovine horn powder (BHP) as an available and low-cost waste material to a value-added highly recyclable catalyst. This green catalyst was prepared through the immobilization of BHP, as a natural keratin resource, on the magnetic Fe₃O₄ nanoparticles. The successful preparation of the catalyst was fully investigated using Fourier transform infrared, X-ray diffraction, and energy-dispersive X-ray spectroscopies as well as field emission scanning electron microscopy, vibrating sample magnetometry, and thermogravimetry. The catalytic efficiency of the prepared magnetic organocatalyst was evaluated in the synthesis of a large series of amide derivatives through the solvent-free transamidation reaction of different amides and amines with yields of 75–96%.

The conversion of bovine horn powder as an available and low-cost waste material to a value-added recyclable organocatalyst for transamidation reaction.     

Janus nanocarriers for magnetically targeted and hyperthermia-enhanced curcumin therapy of liver cancer

Curcumin is regarded as a promising chemotherapeutic agent due to its anti-cancer activity and excellent biosafety. Nevertheless, the poor bioavailability and insufficient therapeutic efficacy have limited its further application in the clinic. Hence, we designed Janus magnetic mesoporous silica nanoparticles (Janus M-MSNs) for magnetically targeted and hyperthermia-enhanced curcumin treatment of liver cancer. In this study, curcumin was loaded into the silica components of Janus M-MSNs via surface-decorated pH-sensitive groups. Janus M-MSNs-Cur exhibited superior superparamagnetic properties, high curcumin loading ability and a tumor microenvironment-responsive curcumin release fashion. Additionally, an external magnetic field promoted the anti-tumor effectiveness of Janus M-MSNs-Cur through increasing the cellular internalization of Janus M-MSNs-Cur. More importantly, magnetic hyperthermia therapy supplemented the chemotherapeutic effect through a synergistic effect. Our outcomes demonstrated that Janus M-MSNs-Cur possessed a high therapeutic efficiency and excellent biosafety both in vitro and in vivo, indicating that Janus M-MSNs-Cur might be a promising therapeutic agent for liver cancer treatment.

Curcumin is regarded as a promising chemotherapeutic agent due to its anti-cancer activity and excellent biosafety.     

Supramolecular self-associating amphiphiles (SSAs) as nanoscale enhancers of cisplatin anticancer activity

Many chemotherapeutic drugs have a narrow therapeutic window due to inefficient tumour cell permeation. Supramolecular self-associating amphiphilic salts (SSAs) are a unique class of small molecules that offer potential as next generation cancer drugs and/or therapeutic enhancement agents. Herein, we demonstrate the cytotoxicity of seven SSAs towards both ovarian and glioblastoma cancer cells. We also utilize the intrinsic fluorescent properties of one of these lead SSAs to provide evidence for this class of compound to both bind to the exterior cancer cell surface and permeate the cell membrane, to become internalized. Furthermore, we demonstrate synergistic effects of two lead SSAs on cisplatin-mediated cytotoxicity of ovarian cancer cells and show that this correlates with increased DNA damage and apoptosis versus either agent alone. This work provides the first evidence that SSAs interact with and permeate cancer cell membranes and enhance the cytotoxic activity of a chemotherapeutic drug in human cancer cells.

Herein we show the potential SSA technology towards the development of synergistic next-generation anticancer treatments.     

Photostable near-infrared-absorbing diradical-platinum(ii) complex solubilized by albumin toward a cancer photothermal therapy agent

A hydrophobic diradical-platinum(ii) complex was solubilized in aqueous solutions by using bovine serum albumin and exhibited photothermal conversion under near-infrared (NIR) light irradiation. The complex was introduced into cancer cells and induced cell death upon absorption of NIR. These results imply that the complex can function as a photothermal therapeutic agent.

A near-infrared (NIR) absorbing diradical-platinum(ii) complex solubilized in PBS by albumin can kill MCF-7 cells by the photothermal effect.     

Ruthenium complexes of sterically-hindered pentaarylcyclopentadienyl ligands

The synthesis of ruthenium complexes incorporating an overcrowded pentaarylcyclopentadienyl ligand has been investigated, and higher efficiency has been reached using chlorine-functionalised precursors when compared with their brominated counterparts. A new methodology for the preparation of chlorocyclopentadienes has been developed which is well adapted for highly sterically hindered compounds and works with either electron rich or poor systems.

Preparation of chlorine functionalised intermediates has been developed which is well adapted for highly sterically hindered compounds both with either electron rich or poor systems.     

Metal-free hypervalent iodine/TEMPO mediated oxidation of amines and mechanistic insight into the reaction pathways

A highly efficient metal free approach for the oxidation of primary and secondary amines to their corresponding aldehydes and ketones using PhI(OAc)₂ in combination with a catalytic amount of TEMPO as an oxidizing agent is described. This protocol is rapid and provides diverse products under milder reaction conditions in excellent yields. In addition, the mechanistic study is well demonstrated by spectroscopic methods.

A highly efficient, metal free rapid protocol studied mechanistically the oxidation of primary and secondary amines to their corresponding carbonyl compounds using PhI(OAc)₂ and catalytic TEMPO to provide diverse products in excellent yields.