Nanomaterials promote the fast development of electrochemical MiRNA biosensors.

Cancer has become the leading cause of death worldwide. In recent years, molecular diagnosis has demonstrated great potential in the prediction and diagnosis of cancer. MicroRNAs (miRNAs) are short oligonucleotides that regulate gene expression and cell function and are considered ideal biomarkers for cancer detection, diagnosis, and patient prognosis. Therefore, the specific and sensitive detection of ultra-low quantities of miRNA is of great significance. MiRNA biosensors based on electrochemical technology have advantages of high sensitivity, low cost and fast response. Nanomaterials show great potential in miRNA electrochemical detection and promote the rapid development of electrochemical miRNA biosensors. Some methods and signal amplification strategies for miRNA detection in recent years are reviewed herein, followed by a discussion of the latest progress in electrochemical miRNA detection based on different types of nanomaterial. Future perspectives and challenges are also proposed for further exploration of nanomaterials to bring breakthroughs in electrochemical miRNA detection.

Defect compensation and intervalence charge transfer state-based Pr3+-doped niobate antithermal quenching phosphors.

Herein, a scheme of Sr2+/Ca2+ ion substitution was employed to simultaneously regulate the defect and intervalence charge transfer (IVCT) state of Sr2-xCaxNb2O7:Pr3+ phosphors, resulting in a dual-modulation strategy for enhancing phosphor thermal stability.

Cubic Na0.5Bi0.5TiO3 nanoperovskite significantly expands the application of sensitive immunosensor for the detection of carcinoembryonic antigen.

Nanosized sodium bismuth perovskite titanate (NBT) was synthesized and first used as the electrochemical immune sensing platform for the sensitive detection of carcinoembryonic antigen (CEA). Gold nanoparticles (Au NPs) grew on the surface of NBT through forming Au-N bond to obtain Au@NBT, and a label-free electrochemical immunosensor was proposed using Au@NBT as an immunosensing recognizer towards CEA. The well-ordered crystal structure of NBT was not changed at all after the modification of Au NPs outside, but significantly improved the conductivity, catalytic activity, and biocompatibility of the Au@NBT-modified electrode. The unique cubic crystal nanostructure of NBT offered a large active area for both Au NP modification and the subsequent immobilization of biomolecules over the electrode surface, triggering the effective generation of promising properties of the proposed Au@NBT-based electrochemical immunosensor. As expected, favorable detection performances were achieved using this immunosensor towards CEA detection, where a good linear relationship between the current response and CEA concentration was obtained in the concentration range 10 fg mL-1 to 100 ng mL-1 with a low detection limit (LOD) of 13.17 fg mL-1. Also, the significantly enhanced selectivity, and stability guaranteed the promising electrochemical properties of this immunosensor. Furthermore, the analysis of real serum samples verified the high feasibility of this new method in clinical CEA detection. This work opens a new window for the application of nanoperovskite in the early detection of CEA.

Hydrangea-like TiO2/Bi2MoO6 porous nanoflowers triggering highly sensitive electrochemical immunosensing to tumor marker.

Rapid and sensitive detection of carcinoembryonic antigen (CEA) is of great significance for cancer patients. Here, molybdenum (Mo) was doped into bismuth oxide (Bi2O3) by one-pot hydrothermal method forming porous tremella Bi2MoO6 nanocomposites with a larger specific surface area than the spherical structure. Then, a new kind of hydrangea-like TiO2/Bi2MoO6 porous nanoflowers (NFs) was prepared by doping titanium into Bi2MoO6, where titanium dioxide (TiO2) grew in situ on the surface of Bi2MoO6 nanoparticles (NPs). The hydrangea-like structure provides larger specific surface area, higher electron transfer ability and biocompatibility as well as more active sites conducive to the attachment of anti-carcinoembryonic antigen (anti-CEA) to TiO2/Bi2MoO6 NFs. A novel label-free electrochemical immunosensor was then constructed for the quantitative detection of CEA using TiO2/Bi2MoO6 NFs as sensing platform, showing a good linear relationship with CEA in the concentration range 1.0 pg/mL ~ 1.0 mg/mL and a detection limit of 0.125 pg/mL (S/N = 3). The results achieved with the designed immunosensor are comparable with many existing immunosensors used for the detection of CEA in real samples.

Recent advances in photothermal nanomaterials-mediated detection of circulating tumor cells.

Photothermal materials have shown great potential for cancer detection and treatment due to their excellent photothermal effects. Circulating tumor cells (CTCs) are tumor cells that are shed from the primary tumor into the blood and metastasize. In contrast to other tumor markers that are free in the blood, CTCs are a collective term for all types of tumor cells present in the peripheral blood, a source of tumor metastasis, and clear evidence of tumor presence. CTCs detection enables early detection, diagnosis and treatment of tumors, and plays an important role in cancer prevention and treatment. This review summarizes the application of various photothermal materials in CTC detection, including gold, carbon, molybdenum, phosphorus, etc. and describes the significance of CTC detection for early tumor diagnosis and tumor prognosis. Focus is also put on how various photothermal materials play their roles in CTCs detection, including CT, imaging and photoacoustic and therapeutic roles. The physicochemical properties, shapes, and photothermal properties of various photothermal materials are discussed to improve the detection sensitivity and efficiency and to reduce the damage to normal cells. These photothermal materials are capable of converting radiant light energy into thermal energy for highly-sensitive CTCs detection and improving their photothermal properties by various methods, and have achieved good results in various experiments. The use of photothermal materials for CTCs detection is becoming more and more widespread and can be of significant help in early cancer screening and later treatment.

Topochemical-like bandgap regulation engineering: A bismuth thiooxide nanocatalyst for breast cancer phototherapy.

The physical property tuning of nanomaterials is of great importance in energy, medicine, environment, catalysis, and other fields. Topochemical synthesis of nanomaterials can achieve precise control of material properties. Here, we synthesized a kind of element-doped bismuth-based nanomaterial (BOS) by topochemical-like synthesis and used it for the phototherapy of tumors. In this study, we employed bismuth fluoride nanoflowers as a template and fabricated element-doped bismuth oxide nanoflowers by reduction conditions. The product is consistent with the precursor in crystal structure and nanomorphology, realizing topochemical-like synthesis under mild conditions. BOS can generate reactive oxygen species, consume glutathione, and perform photothermal conversion under 730 nm light irradiation. In vitro and in vivo studies demonstrate that BOS could suppress tumor growth by inducing apoptosis and ferroptosis through phototherapy. Therefore, this study offers a general regulation method for tuning the physical properties of nanomaterials by using a topochemical-like synthesis strategy.

Thermal activation induced charge transfer state absorption redshift realizes strong anti-thermal quenching in Pr3+-activated phosphor.

In our work, a totally anomalous thermal quenching phenomenon of red-shifted and enhanced charge transfer state (CTS) absorption is found for the first time in LiTaO3:xPr3+ phosphors. The crystal structure, luminescent properties and the mechanism of abnormal thermal quenching were investigated in detail.

Regulating Luminescence Thermal Quenching of Praseodymium-Doped Niobo-Tantalate Phosphor through Intervalence Charge Transfer Band Displacement.

Pr3+-related intervalence charge transfer (IVCT) bands are a research hotspot owing to their amelioration in the luminescence thermal quenching of Pr3+-activated phosphors. Here, a typical IVCT band displacement strategy via a topological chemical scheme is reported to optimize the luminescence thermal quenching performance of praseodymium-doped niobo-tantalate. The substitution of Ta5+ ions for Nb5+ ions reduces the valence-weighted average cation optical electronegativity and increases the bond lengths of the activator (Pr3+) to the ligand cations (Nb5+ and Ta5+) via adjusting the crystal structure, leading to an increase in the IVCT energy level position from 3.521 to 4.139 eV. The increase in the IVCT energy level leads to an increase in the number of electrons located in the Pr3+ 3P0 energy level, which compensates for the emission of 1D2 during warming. Especially, the energy gap value of the IVCT band is positively correlated with the thermal quenching activation energy ΔE2. ΔE2 increases, the crossover point rises, and the nonradiative transition decreases, further enhancing the Pr3+ 1D2 emission. At 503 K, the 1D2 emission integral intensity increases from 14 to 224% relative to the 303 K original integral intensity. This IVCT band displacement strategy can be used as a scheme for designing antithermal quenching luminescence materials.

Enhancement Effects and Mechanism Studies of Two Bismuth-Based Materials Assisted by DMSO and Glycerol in GC-Rich PCR.

Polymerase chain reaction (PCR) has extensive bioanalytical applications in molecular diagnostics and genomic research studies for rapid detection and precise genomic amplification. Routine integrations for analytical workflow indicate certain limitations, including low specificity, efficiency, and sensitivity in conventional PCR, particularly towards amplifying high guanine-cytosine (GC) content. Further, there are many ways to enhance the reaction, for example, using different PCR strategies such as hot-start/touchdown PCR or adding some special modifications or additives such as organic solvents or compatible solutes, which can improve PCR yield. Due to the widespread use of bismuth-based materials in biomedicine, which have not yet been used for PCR optimization, this attracts our attention. In this study, two bismuth-based materials that are inexpensive and readily available were used to optimize GC-rich PCR. The results demonstrated that ammonium bismuth citrate and bismuth subcarbonate effectively enhanced PCR amplification of the GNAS1 promoter region (∼84% GC) and APOE (75.5% GC) gene of Homo sapiens mediated by Ex Taq DNA polymerase within the appropriate concentration range. Combining DMSO and glycerol additives was critical in obtaining the target amplicons. Thus, the solvents mixed with 3% DMSO and 5% glycerol were used in bismuth-based materials. That allowed for better dispersion of bismuth subcarbonate. As for the enhanced mechanisms, the surface interaction of PCR components, including Taq polymerase, primer, and products with bismuth-based materials, was maybe the main reason. The addition of materials can reduce the melting temperature (Tm), adsorb polymerase and modulate the amount of active polymerase in PCR, facilize the dissociation of DNA products, and enhance the specificity and efficiency of PCR. This work provided a class of candidate enhancers for PCR, deepened our understanding of the enhancement mechanisms of PCR, and also explored a new application field for bismuth-based materials.

Exploring the Inhibitory Effect of AgBiS2 Nanoparticles on Influenza Viruses.

Influenza viruses are respiratory pathogens that are major threats to human health. Due to the emergence of drug-resistant strains, the use of traditional anti-influenza drugs has been hindered. Therefore, the development of new antiviral drugs is critical. In this article, AgBiS2 nanoparticles were synthesized at room temperature, using the bimetallic properties of the material itself to explore its inhibitory effect on the influenza virus. By comparing the synthesized Bi2S3 and Ag2S nanoparticles, it is found that after adding the silver element, the synthesized AgBiS2 nanoparticles have a significantly better inhibitory effect on influenza virus infection than Bi2S3 and Ag2S nanoparticles. Recent studies have shown that the inhibitory effect of AgBiS2 nanoparticles on the influenza virus mainly occurs in the stages of influenza virus-cell internalization and intracellular replication. In addition, it is found that AgBiS2 nanoparticles also have prominent antiviral properties against α and ß coronaviruses, indicating that AgBiS2 nanoparticles have significant potential in inhibiting viral activity.

Adjustment of Bi3+ Luminescence and Thermal Quenching Properties by B'-Site Ion Substitution Strategy in Double Perovskite CaLaMgSb/TaO6:Bi3+ Phosphor.

Thermal quenching has always been one of the most difficult issues in creating high-quality phosphor conversion light-emitting diodes (pc-LED), and a family of strategies are urgently needed to improve the luminescence performance of phosphors at high temperatures. In this contribution, a novel B'-site substitution CaLaMgSbxTa1-xO6:Bi3+ phosphor was constructed using an ion substitution strategy in the matrix with a green activator Bi3+ and a novel double perovskite material. When Sb5+ replaces Ta5+, a surprising increase in luminescence intensity occurs and the thermal quenching properties are greatly improved. The shift of the Raman characteristic peak to a smaller wavenumber and the reduction of the Bi-O bond length confirm that the crystal field environment around Bi3+ changes, which has a substantial effect on the crystal field splitting and nepheline effect of Bi3+ ions, affecting the crystal field splitting energy (Dq). This results in a corresponding increase of the band gap and the thermal quenching activation energy (ΔE) of the activator Bi3+. From the perspective of Dq, the intrinsic relationships among the activator ion band gap, bond length, and Raman characteristic peak changes were analyzed, and a mechanism for regulating luminescence thermal quenching properties was constructed, which provides an effective strategy for improving the promising new materials such as double perovskite.

Virtual Screening-Based Study of Novel Anti-Cancer Drugs Targeting G-Quadruplex.

In order to develop new anti-cancer drugs more efficiently and reduce side effects based on active drug targets, the virtual drug screening was carried out through the target of G-quadruplexes and 23 hit compounds were, thus, screened out as potential anticancer drugs. Six classical G-quadruplex complexes were introduced as query molecules, and the three-dimensional similarity of molecules was calculated by shape feature similarity (SHAFTS) method so as to reduce the range of potential compounds. Afterwards, the molecular docking technology was utilized to perform the final screening followed by the exploration of the binding between each compound and four different structures of G-quadruplex. In order to verify the anticancer activity of the selected compounds, compounds 1, 6 and 7 were chosen to treat A549 cells in vitro, the lung cancer epithelial cells, for further exploring their anticancer activity. These three compounds were found to be of good characteristics in the treatment of cancer, which revealed the great application prospect of the virtual screening method in developing new drugs.

Pt Nanodot Inlaid Mesoporous NaBiOF Nanoblackberry for Remarkable Signal Amplification Toward Biomarker Detection.

A new ultrasensitive sandwich-type electrochemical immunosensor has been successfully constructed to quantitatively detect carcinoembryonic antigen (CEA) using blackberry-like mesoporous bismuth-based nanospheres NaBiOF (NBOF NSs) inlaid with Pt nanodots (NDs) (BiPt NSs) as the antibody capture and signal-amplifying probe. The growth of Pt NDs inside the holes of NBOF NSs formed the nanozyme inlay outside NBOF NSs, greatly increasing the specific surface area and exposure of the catalytic active sites by minimizing the particle size of the Pt to nanodot scale. Such a blackberry-shaped heterojunction structure of BiPt NSs was well-suited to antibody capture and improved the catalytic performance of BiPt NSs in reducing H2O2, amplifying the signal, and yielding highly sensitive detection of CEA. The use of Au nanoparticle-modified multi-walled carbon nanotubes (Au@MWCNTs) as the electrode substrates significantly enhanced the electron transfer behavior over the electrode surface, further increasing the conductivity and sensitivity of the immunosensor. Remarkably, good compatibility with human body fluid was achieved using the newly developed BiPt-based immunosensor resulting from the favorable biocompatibility and stability of both BiPt NSs and Au@MWCNTs. Benefiting from the double signal amplification strategy and the high biocompatibility, the immunosensor responded linearly to CEA in a wide range from 50 fg/mL to 100 ng/ml with an extremely low detection limit of 3.52 fg/mL (S/N = 3). The excellent detection properties of this new immunosensor were evidenced by the satisfactory selectivity, reproducibility, and stability obtained, as well as the reliable and precise determination  of CEA in actual human blood samples. This work provides a new strategy for the early clinical diagnosis of cancer. Novel blackberry-like mesoporous NaBiOF nanospheres with Pt nanodot inlay were successfully usedto construct a sandwich-type electrochemical immunosensor for the ultra-sensitive detection ofcarcinoembryonic antigen in human blood plasma based on a remarkable signal amplification strategy.

Potent saccharinate-containing palladium(II) complexes for sensitization to cancer therapy.

Palladium(II) (PdII) complexes are among the most promising anticancer compounds. Both 2`-benzoylpyridine thiosemicarbazone (BpT) and saccharinate (Sac) are efficient metal chelators with potent anticancer activity. To explore a more effective new anticancer drug, we synthesized a series of Sac and BpT-containing PdII complexes coordinated with thiosemicarbazone (TSC)-derived ligands, and characterized them through nuclear magnetic resonance (NMR), Fourier transformed infrared spectroscopy (FT-IR), elemental analysis, ultraviolet-visible spectroscopy (UV-Vis) and thermogravimetric analysis (TGA). Each target complex was composed of PdII, BpT, and one or two Sac molecules. Both the in vitro and in vivo anti-growth effects of those ligands and the obtained PdII complexes were investigated in the human lung adenocarcinoma cell lines A549 and Spc-A1. The coordination of PdII with the TSC-derivatives and Sac resulted in clearly greater anticancer activity than single ligands. These compounds were demonstrated to be safe for 293 T normal human kidney epithelial cells. The introduction of Sac into the TSC-derived PdII complex significantly enhanced anti-growth effects, and induced apoptosis of human lung cancer cells in vitro and in vivo in a dose dependent manner. Moreover, the PdII complex containing two Sac molecules showed the most promising therapeutic effects, thereby confirming that Sac increases the cancer therapeutic efficacy of PdII complexes and providing a new strategy for exploring anticancer drugs for potential clinical treatment.

Recent advances in stimuli-responsive nano-heterojunctions for tumor therapy.

Stimuli-responsive catalytic therapy based on nano-catalysts has attracted much attention in the field of biomedicine for tumor therapy, due to its excellent and unique properties. However, the complex tumor microenvironment conditions and the rapid charge recombination in the catalyst limit catalytic therapy's effectiveness and further development. Effective heterojunction nanomaterials are constructed to address these problems to improve catalytic performance. Specifically, on the one hand, the band gap of the material is adjusted through the heterojunction structure to promote the charge separation efficiency under exogenous stimulation and further improve the catalytic capacity. On the other hand, the construction of a heterojunction structure can not only preserve the function of the original catalyst but also achieve significantly enhanced synergistic therapy ability. This review summarized the construction and functions of stimuli-responsive heterojunction nanomaterials under the excitation of X-rays, visible-near infrared light, and ultrasound in recent years, and further introduces their application in cancer therapy. Hopefully, the summary of stimuli-responsive heterojunction nanomaterials' applications will help researchers promote the development of nanomaterials in cancer therapy.

Recent Development of Rhenium-Based Materials in the Application of Diagnosis and Tumor Therapy.

Rhenium (Re) is widely used in the diagnosis and treatment of cancer due to its unique physical and chemical properties. Re has more valence electrons in its outer shell, allowing it to exist in a variety of oxidation states and to form different geometric configurations with many different ligands. The luminescence properties, lipophilicity, and cytotoxicity of complexes can be adjusted by changing the ligand of Re. This article mainly reviews the development of radionuclide 188Re in radiotherapy and some innovative applications of Re as well as the different therapeutic approaches and imaging techniques used in cancer therapy. In addition, the current application and future challenges and opportunities of Re are also discussed.

Two Hawks with One Arrow: A Review on Bifunctional Scaffolds for Photothermal Therapy and Bone Regeneration.

Despite the significant improvement in the survival rate of cancer patients, the total cure of bone cancer is still a knotty clinical challenge. Traditional surgical resectionof bone tumors is less than satisfactory, which inevitably results in bone defects and the inevitable residual tumor cells. For the purpose of realizing minimal invasiveness and local curative effects, photothermal therapy (PTT) under the irradiation of near-infrared light has made extensive progress in ablating tumors, and various photothermal therapeutic agents (PTAs) for the treatment of bone tumors have thus been reported in the past few years, has and have tended to focus on osteogenic bio-scaffolds modified with PTAs in order to break through the limitation that PTT lacks, osteogenic capacity. These so-called bifunctional scaffolds simultaneously ablate bone tumors and generate new tissues at the bone defects. This review summarizes the recent application progress of various bifunctional scaffolds and puts forward some practical constraints and future perspectives on bifunctional scaffolds for tumor therapy and bone regeneration: two hawks with one arrow.

Ti3C2@Bi2O3 nanoaccordion for electrochemical determination of miRNA-21.

Based on a dual signal amplification strategy of novel accordion-like Bi2O3-decorated Ti3C2 (Ti3C2@Bi2O3) nanocomposites and hybridization chain reaction (HCR), an ultra-sensitive electrochemical biosensor was constructed for miRNA-21 detection. By etching Ti3AlC2 with HF, Ti3C2 with an accordion-like structure was first obtained and subsequently covered by Bi2O3 nanoparticles (NPs), forming Ti3C2@Bi2O3. A layer of Au NPs was electrodeposited on the glassy carbon electrode coated with Ti3C2@Bi2O3, which not only significantly improved the electron transport capacity of the electrode but also greatly increased its surface active area. Upon the immobilization of the thiolated capture probe (SH-CP) on the electrode, the target miRNA-21 specifically hybridized with SH-CP and thus opened its hairpin structure, triggering HCR to form a long double strand with the primers H1 and H2. A large number of the electrochemical indicator molecules were thus embedded inside the long double strands to produce the desirable electrochemical signal at a potential of - 0.19 V (vs. Ag/AgCl). Such dual signal amplification strategy successfully endowed the biosensor with ultra-high sensitivity for miRNA-21 detection in a wide linear range from 1 fM to 100 pM with a detection limit as low as 0.16 fM. The excellent detection of miRNA-21 in human blood plasma displayed a broad prospect in clinical diagnosis. An ultra-sensitive electrochemical biosensor was successfully constructed for miRNA-21 detection in human blood plasma based on the dual signal amplification strategy of novel accordion-like Bi2O3 decorated Ti3C2 (Ti3C2@Bi2O3) nanocomposites and hybridization chain reaction.

Efficient improvement in chemo/photothermal synergistic therapy against lung cancer using Bi@Au nano-acanthospheres.

Novel highly hydrophilic and biocompatible bismuth nanospheres with gold nanoparticles growing outside (Bi@Au nano-acanthospheres, Bi@Au NASs) were synthesized through a simple procedure, which demonstrated to be a promising photothermal agent owing to the ultrahigh photothermal conversion efficiency (η = 46.6 %). The as-prepared Bi@Au NASs showed excellent blood compatibility and fairly low cytotoxicity to human lung cancer A549 cells, as well as efficient photothermal ablation (PTA) therapy induced by a near-infrared laser. Under the 808 nm laser radiation, the tumour temperature could be elevated by ∼25 °C high enough to kill the cancer cells. Moreover, the anticancer drug doxorubicin hydrochloride (DOX) was successfully loaded in Bi@Au NASs with a loading content as high as 16.78 % and released under a pH sensitive release profile, a characteristic beneficial for intravenous delivery of DOX into cancer cells for chemotherapy. The presence of the Bi element enabled Bi@Au NASs to act as a favourable computed tomography (CT) contrast medium for CT imaging-guided tumour treatment. Compared with cancer treatment through either photothermal therapy or chemotherapy, the chemo-photothermal synergistic therapy using Bi@Au NASs as both a photothermal agent and a drug carrier has efficiently enhanced the in vitro and in vivo therapeutic effects in cancer treatment.

Application of Nanomaterials to Enhance Polymerase Chain Reaction.

Polymerase Chain Reaction (PCR) is one of the most common technologies used to produce millions of copies of targeted nucleic acid in vitro and has become an indispensable technique in molecular biology. However, it suffers from low efficiency and specificity problems, false positive results, and so on. Although many conditions can be optimized to increase PCR yield, such as the magnesium ion concentration, the DNA polymerases, the number of cycles, and so on, they are not all-purpose and the optimization can be case dependent. Nano-sized materials offer a possible solution to improve both the quality and productivity of PCR. In the last two decades, nanoparticles (NPs) have attracted significant attention and gradually penetrated the field of life sciences because of their unique chemical and physical properties, such as their large surface area and small size effect, which have greatly promoted developments in life science and technology. Additionally, PCR technology assisted by NPs (NanoPCR) such as gold NPs (Au NPs), quantum dots (QDs), and carbon nanotubes (CNTs), etc., have been developed to significantly improve the specificity, efficiency, and sensitivity of PCR and to accelerate the PCR reaction process. This review discusses the roles of different types of NPs used to enhance PCR and summarizes their possible mechanisms.