Search

Background The rapid spread of infectious bacteria has brought great challenges to public health. It is imperative to explore effective and environment-friendly antibacterial modality to defeat antibiotic-resistant bacteria with high biosafety and broad-spectrum antibacterial property. Results Herein, biocompatible Cu3SnS4 nanoflakes (NFs) were prepared by a facile and low-cost fabrication procedure. These Cu3SnS4 NFs could be activated by visible light, leading to visible light-mediated photocatalytic generation of a myriad of reactive oxygen species (ROS). Besides, the plasmonic Cu3SnS4 NFs exhibit strong near infrared (NIR) absorption and a high photothermal conversion efficiency of 55.7%. The ROS mediated cellular oxidative damage and the NIR mediated photothermal disruption of bacterial membranes collaboratively contributed to the advanced antibacterial therapy, which has been validated by the efficient eradication of both Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus strains in vitro and in vivo. Meanwhile, the exogenous copper ions metabolism from the Cu3SnS4 NFs facilitated the endothelial cell angiogenesis and collagen deposition, thus expediting the wound healing. Importantly, the inherent localized surface plasmon resonance effect of Cu3SnS4 NFs empowered them as an active substrate for surface-enhanced Raman scattering (SERS) imaging and SERS-labeled bacteria detection. Conclusions The low cost and biocompatibility together with the solar-driven broad-spectrum photocatalytic/photothermal antibacterial property of Cu3SnS4 NFs make them a candidate for sensitive bacteria detection and effective antibacterial treatment. Graphical Abstract

The rapid spread of infectious bacteria has brought great challenges to public health. It is imperative to explore effective and environment-friendly antibacterial modality to defeat antibiotic-resistant bacteria with high biosafety and broad-spectrum antibacterial property.Herein, biocompatible CuThe low cost and biocompatibility together with the solar-driven broad-spectrum photocatalytic/photothermal antibacterial property of Cu

Hypoxemia after acute myocardial infarction (AMI) causes severe damage to cardiac cells and induces cardiac dysfunction. Protection of cardiac cells and reconstruction of cardiac functions by re-introducing oxygen into the infarcted myocardium represents an efficient approach for the treatment of AMI. However, the established methods for oxygen supplementation mainly focus on systemic oxygen delivery, which always results in inevitable oxidative stress on normal tissues. In this work, an ultrasound (US) activated oxygen generation nanosystem has been developed, which specifically releases oxygen in the infarcted myocardium and alleviates the hypoxemic myocardial microenvironment to protect cardiac cells after AMI. The nanosystem was constructed through the formation of calcium peroxide in the mesopores of biocompatible mesoporous silica nanoplatforms, followed by the assembly of the thermosensitive material heneicosane and polyethyleneglycol. The mild hyperthermia induced by US irradiation triggered the phase change of heneicosane, thus achieving US responsive diffusion of water and release of oxygen. The US-activated oxygen release significantly alleviated the hypoxia and facilitated the mitigation of oxidative stress after AMI. Consequently, the survival of cardiac cells under hypoxic conditions was substantially improved and the damage in the infarcted myocardial tissue was minimized. This US-activated oxygen generation nanosystem may provide an efficient modality for the treatment of AMI.

Tumor hypoxia is a negative prognostic factor in cancer radiotherapy, due in part to its role in causing resistance to radiotherapy. It has attracted extensive critical attention to radiation sensitizers by using active oxygen to improve radiotherapy outcome. Active oxygen delivery functional materials are promising candidates to transport active oxygen to tumor cells. Herein, we report an oxygen delivery functional material by using hollow mesoporous silica nanoparticles (HMSNs) as carriers, synthesizing sodium percarbonate (SPC) in the channels and cavity of HMSNs (SPC@HMSNs) and coating polyacrylic acid (PAA) on the functional materials (SPC@HMSNs–PAA). SPC@HMSNs–PAA could release more SPC in a simulated tumor acidic microenvironment (pH ∼ 6.5), which can provide oxygen to improve radiotherapy outcome even under low energy X-ray irradiation. The events induce obvious overproduction of reactive oxygen radicals to kill cancer cells with a significant effect. Meanwhile, no obvious cytotoxicity was observed when SPC@HMSNs–PAA applied alone. The radiosensitization of SPC@HMSNs–PAA on cancer cells, even exposure to low-energy X-ray irradiation, may suggest promising application in radiotherapy.

Discography often destroys the hypoxic environment in the intervertebral disc and accelerates intervertebral disc degeneration (IVDD). Therefore, it often fails to meet the requirements for application in clinical practice. This technology mainly increases the reactive oxygen species (ROS) in the IVD. As so, it is particularly critical to develop strategies to avoid this degeneration mechanism. Prussian blue nanoparticles (PBNPs) are found to enhance development under magnetic resonance T1 and have antioxidant enzyme activity. The key results of the present study confirm that PBNPs alleviate intracellular oxidative stress and increase the intracellular activities of antioxidant enzymes, such as superoxide dismutase 1 (SOD1). PBNPs can rescue nucleus pulposus cell degeneration by increasing oxidoreductase system-related mRNA and proteins, especially by stabilizing SOD1 from ubiquitination-proteasome degradation, thus improving the mitochondrial structure to increase antioxidation ability, and finally rescuing ROS-induced IVDD in a rat model. Therefore, it is considered that PBNPs can be a potential antioxidation-protective discography contrast agent.

We describe a fully stereodivergent synthesis of a range of α,α-disubstituted α-amino acids via an Ir/Cu-catalyzed α-allylation of readily available imine esters. The introduction of a Cu-Phox complex-activated imine ester into the chiral iridium-catalyzed allylic allylation process is crucial for its high reactivity and excellent enantio- and diastereoselectivity (up to >99% ee and >20:1 dr). Importantly, the two chiral catalysts allow for full control over the configuration of the stereocenters, affording all stereoisomers of the desired products. The utility of this methodology was demonstrated by synthesizing dipeptides and analogues of bioactive molecules in a stereodivergent manner.

The asymmetric allylation of glycine iminoesters has been accomplished through a synergistic Pd/Cu catalyst system, affording a range of α-substituted α-amino acids in high yields and with excellent enantioselectivities (88 → 99% ee). The introduction of a Cu-P,N-metallocenyl complex-activated glycine iminoester to the chiral palladium-catalyzed allylic allylation process is crucial owing to its high reactivity and excellent enantioselectivities. Importantly, this Pd/Cu dual catalysis strategy can be used for the asymmetric allylic alkylation of prochiral glycine amide derivatives, which could be further utilized to synthesize biologically important vicinal diamines.

Allylic alcohols and allylic amines were directly utilized in a Pd-catalyzed hydrogen-bond-activated allylic amination under mild reaction conditions in the absence of any additives. The cooperative action of a Pd-catalyst and a hydrogen-bonding solvent is most likely responsible for its high reactivity. The catalytic system is compatible with a variety of functional groups and can be used to prepare a wide range of linear allylic amines in good to excellent yields. Furthermore, this methodology can be easily applied to the one-step synthesis of two drugs, cinnarizine and naftifine, on a gram scale.

Conventional chemotherapy uses potent toxic drugs to destroy cancer cells and always causes severe systemic toxicity in patients. In this respect, a smart and pH-switched prodrug/procatalyst co-delivery nanosystem is developed which is non-toxic toward normal cells and is inert during its delivery in the vasculature, while responsively functions in acidic lysosomes inside cancer cells. Synthetically, non-toxic artemisinin (ART) was used as the prodrug and loaded into the inner space of hollow mesoporous silica (HMS) nanoparticles (NPs). Subsequently, Fe3O4 NPs were efficiently capped onto pore outlets of HMS via acid labile acetal linkers (ART@HMS-Fe3O4). ART@HMS-Fe3O4 was stable under neutral conditions (pH 7.4) with almost no leakage of ART. Upon exposure to the acidic lysosomal compartment (pH 3.8–5.0) in cells, the acetal linkers were hydrolyzed which led to sustained release of both ART and Fe3O4 NPs. Under the activation of the lysosomal environment, the liberated Fe3O4 NPs were metabolized to free iron ions and catalyzed the generation of high amounts of free radicals from the released ART in cells. In vitro cytotoxicity assay revealed excellent anticancer efficacy of this ART/Fe3O4 co-delivery nanosystem. The Fe3O4 NPs acted both as gatekeepers and procatalysts which inhibited ART from leakage during their delivery, while released ART and activated chain reactions to form free radicals in acidic lysosomes inside cancer cells. We visualize that this lysosomal environment-responsive ART@HMS-Fe3O4 nanosystem could serve as an efficient and desirable chemotherapeutic nanosystem for cancer therapy.

Hypoxia has been firmly correlated to the drug resistance of solid tumors. Alleviation of hypoxia by tumor reoxygenation is expected to sensitize the chemotherapy toward solid tumors. Alternatively, ferroptosis provides a therapeutic strategy to overcome apoptotic resistance and multidrug resistance of solid tumors, collaboratively strengthening the chemotherapy toward hypoxic tumors. Herein, an ultrasound (US)-activatable nanomedicine was developed for overcoming hypoxia-induced resistance to chemotherapy and efficiently inhibiting tumor growth by inducing sensitized apoptosis and collaborative ferroptosis of tumor cells. This nanomedicine was constructed by integrating ferrate and doxorubicin into biocompatible hollow mesoporous silica nanoplatforms, followed by assembling a solid-liquid phase-change material of n-heneicosane. The US-induced mild hyperthermia initiates the phase change of n-heneicosane, enabling US-activated co-release of ferrate and doxorubicin. Results reveal that the released ferrate effectively reacts with water as well as the over-expressed hydrogen peroxide and glutathione in tumor cells, achieving tumor-microenvironment-independent reoxygenation and glutathione-depletion in tumors. The reoxygenation down-regulates expressions of hypoxia-inducible factor 1α and multidrug resistance gene/transporter P-glycoprotein in tumor cells, sensitizing the apoptosis-based doxorubicin chemotherapy. More importantly, exogenous iron metabolism from the nanomedicine initiates intracellular Fenton reactions, leading to reactive oxygen species overproduction and iron-dependent ferroptotic death of tumor cells. Furthermore, the glutathione-depletion inactivates the glutathione peroxidase 4 (GPX4, a critical regulatory target in ferroptosis), inhibiting the reduction of lipid peroxides and reinforcing the ferroptotic cell death. The sensitized chemotherapy together with the iron-dependent ferroptosis of tumor cells play a synergistic role in boosting the growth suppression of hypoxic osteosarcoma in vivo. Additionally, the nanomedicine acts as a nanoprobe for in vivo photoacoustic imaging and glutathione tracking, showing great potential as theranostic agents for hypoxic solid tumors treatment.

Hydroxyapatite (HAp) nanocrystals as the main inorganic component in hard tissue have been extensively studied for bone regeneration and dental implant treatment. However, failure of surgical reconstruction often occurs owing to the lack of effective antibacterial ability of HAp. It is still a challenge to develop artificial HAp with both efficient antibacterial ability and proper biological properties. Herein, a series of ultra-trace Ag-doped HAp nanocrystals have been elaborately prepared with the optimal doping concentration from 0.27 ppm to 2.2 ppm, which present non-cytotoxicity while possess effective bacteria reduction ability. Ultra-trace Ag-doped HAp nanocrystals possess higher protein adsorption than pure HAp nanocrystals due to the trace doping-induced less negative surface potential. The ultra-trace Ag-doped HAp nanocrystals showed effectively antibacterial ability, non-cytotoxicity and enhanced adsorbability that made them ideal materials for various biocompatible and antibacterial applications.

Excess reactive oxygen species (ROS) have been proved to damage cancer cells efficiently. ROS overproduction is thus greatly desirable for cancer therapy. To date, ROS production is generally uncontrollable and outside cells, which always bring severe side-effects in the vasculature. Since most ROS share a very short half-life and primarily react close to their site of formation, it would be more efficient if excess ROS are controllably produced inside cancer cells. Herein, we report an efficient lysosome-controlled ROS overproduction via a pH-responsive catalytic nanosystem (FeOx-MSNs), which catalyze the decomposition of H2O2 to produce considerable ROS selectively inside the acidic lysosomes (pH 5.0) of cancer cells. After a further incorporation of ROS-sensitive TMB into the nanosystem (FeOx-MSNs-TMB), both a distinct cell labeling and an efficient death of breast carcinoma cells are obtained. This lysosome-controlled efficient ROS overproduction suggests promising applications in cancer treatments.

Synergistic catalysis is gaining increasing attention due to its advantages over traditional catalytic methodologies, such as improved catalytic activity, broader substrate scope, increased selectivity and lower cost. Methodologies involving the synergistic combination of metal catalysts and organocatalysts have been intensively studied. Given the clear benefits of bimetallic catalyst systems consisting of two distinct metal catalysts, cooperative bimetallic catalysis has proved to be successful for a number of difficult asymmetric transformations. This review highlights the recent advances in bimetallic systems for catalytic asymmetric allylic substitution reactions. Strategies using a chiral metal catalyst and the cooperative effect of a second achiral metal catalyst for asymmetric transformations are discussed. Additionally, several challenging asymmetric reactions realized by employing two different chiral metal catalysts in a synergistic manner are also covered.

We report a stereoselective and site-specific allylic alkylation of Schiff base activated amino acids and small peptides via a Pd/Cu dual catalysis. A range of noncoded α,α-dialkyl α-amino acids were easily synthesized in high yields and with excellent enantioselectivities (up to >99% ee). Furthermore, a direct and highly stereoselective synthesis of small peptides with enantiopure α-alkyl or α,α-dialkyl α-amino acids residues incorporated at specific sites was accomplished using this dual catalyst system.

Excessive free radicals are noxious for living organisms and lead to cell death. Destruction of malignant cells by reactive free radicals has been widely used in cancer treatment. A key consideration is how to allow targeted free radical attack on cancer cells and avoid unwanted side-effects. Herein, we develop an efficient intracellular free radical generation strategy against cancer cells by delivering active ingredients into cancer cells, where free radicals are selectively generated by a lysosomal bioactivation process. Artesunate (ART), which is non-toxic to normal cells, was chosen as the free radical source and transported into cells with a hollow mesoporous silica-based delivery system (ART@HMS). To selectively activate the ART@HMS inside cancer cells, a high-bioactive Fe/O cluster-mesoporous silica nanosystem (Fe/O-MSN) was elaborately prepared. Under the bioactivation of the lysosome, the low-dose ART@HMS together with biocompatible Fe/O-MSN induced significant intracellular generation of toxic free radicals and efficient death of cancer cells. This selective intracellular free radical generation strategy is encouraging for its development into an effective low-cost cancer therapy.

d -Amino acid oxidase (DAO), which could catalyze generation of hydrogen peroxide with strong oxidbility and cytotoxicity, has become of interest as a biocatalyst for therapeutic treatments. Herein we report that amino-functional hollow mesoporous silica with large pore size (10.27 nm) and positively charged surface effectively immobilize DAO with negative charge. The adsorption, activity and stability of DAO are demonstrated to depend mainly on the amino-functionalization of surface. Significant cancer cell killing effect is observed when the cells are treated by the nanocapsules entrapping DAO together with d -alanine, showing distinct dose-dependency on concentration of the nanocapsules entrapping DAO or d -alanine. Nevertheless, the toxicity is completely neutralized by the addition of catalase, and anti-tumor effect is not observed when either the nanocapsules entrapping DAO or d -alanine is applied alone. The results indicate that cytotoxicity of the nanocapsules entrapping DAO could be managed by exogenous administration of nontoxic prodrug to tumor tissue, due to the stereoselectivity of DAO and the scarcity of its substrates in mammalian organisms. Thus, the method might be exploited as a potential treatment for cancer therapy.

We herein report the optical diffuse reflection properties of hollow mesoporous silica nanospheres (HMSNs). The HMSNs reflect more than 90% of the UV and visible light in the wide range of 240–800 nm and more than 70% of the UV light shorter than 240 nm, which are significantly higher than that of the bulk silica. The high reflectance of the HMSNs mainly arises from multiple scattering, which is caused by the disordered arrangement of nanospheres with thickness up to several hundred nanometers. Besides, the unique microstructure of HMSNs and the comparable size of HMSNs with UV light may also contribute to their high reflection according to the Mie scattering principles. Unlike semiconductor materials which shield UV light by absorbing UV light and generating reactive species, the HMSNs display extremely low absorption in the UV light region. The high UV light reflection properties as well as the specific hollow mesoporous structures of the HMSNs indicate their superior applications in UV light shielding devices.

β-Cyclodextrin (β-CD)-capped mesoporous silica nanoparticles with hydrophobic internal nanovoids were prepared and used for effective cancer cell killing in synergistic combination with low-energy ultrasound (≤1.0 W cm-2, 1 MHz). The water-dispersible nanoparticles with hydrophobic internal nanovoids can be taken up by cancer cells and subsequently evoke a remarkable cavitation effect under irradiation with mild low-energy ultrasound (≤1.0 W cm-2, 1 MHz). A significant cancer cell killing effect was observed in cancer cells and in a mouse xenograft tumor model treated with the nanoagents together with the low-energy ultrasound, showing a distinct dependence on the concentration of nanoagents and ultrasound intensity. By contrast, an antitumor effect was not observed when either low-energy ultrasound or nanoagents were applied alone. These findings are significant as the technique promises a safe, low-cost, and effective treatment for cancer therapy. Seeds of success: After accumulation in tumors and endocytosis to lysosomes, mesoporous silica nanoparticles with internal hydrophobic mesopores can act as bubble nucleation seeds responding to low-intensity ultrasound. This drastically amplifies the ultrasonic cavitation effect, a process that can disrupt the lysosomal membrane and release lysosomal proteases, thus leading to cell necrosis. Copyright

Free radicals are toxic entities known to cause cellular damage and to mediate cell death. We herein develop a controlled free radical generation strategy for cancer therapy via pH-responsive release of benzoyl peroxide (BPO) in tumor cells and producing free radicals to mediate cell death. BPO as the free radical resource was encapsulated into a chitosan (Cs)-coated mesoporous silica nanocomposite (BPO@HMSNs-Cs). The mesoporous silica carrier improved the BPO solubility by preventing its crystallization and promoted its stability by inclusion. Chitosan imparted the nanocomposite pH-responsive BPO release capacity with enhanced BPO release in simulated acidic tumor media (pH 6.5) and minor release in simulated normal tissue media (pH 7.4). The enhanced free radical generation in tumor media further led to significantly higher cytotoxicity in the tumor at acidic pH 6.5 than at physiological pH 7.4. The free radical-mediated cytotoxicity of BPO@HMSNs-Cs was verified by the observation of free radical-induced green fluorescence in cells. This pH-responsive free radical generation nanocomposite may provide new opportunities for controlled drug delivery and cancer therapy.