Carrier Free O2 -Economizer for Photodynamic Therapy Against Hypoxic Tumor by Inhibiting Cell Respiration.

Abnormal tumor metabolism causes the hypoxic microenvironment, which greatly limits the efficacy of photodynamic therapy (PDT). In this work, a strategy of metabolic reprogramming is proposed to economize O2 for enhanced PDT against hypoxic tumors. The carrier-free O2 -economizer (designated as LonCe) is prepared based on the metabolic antitumor drug of Lonidamine (Lon) and the photosensitizer of chlorin e6 (Ce6). By virtue of intermolecular interactions, Lon and Ce6 self-assemble into nanosized LonCe with favorable stability and high drug contents. Compared with Ce6, LonCe exhibits an improved cellular uptake and photodynamic property for tumor treatment. Moreover, LonCe is capable of inhibiting cell metabolism and mitochondrial respiration to remit the tumor hypoxia, which would promote reactive oxygen species (ROS) production and elevate the PDT efficacy on tumor suppression. In vivo experiments indicate that intravenously injected LonCe prefers to accumulate at the tumor site for highly efficient PDT regardless of the hypoxic environment. Besides, the self-delivery LonCe is fabricated without any carriers, which avoids the excipients induced system toxicity and immunogenicity in vivo. This carrier-free nanomedicine with cell respiratory inhibition mechanism would expedite the development and clinical translation of photodynamic nanoplatforms in tumor treatment.

Carrier Free Photodynamic Synergists for Oxidative Damage Amplified Tumor Therapy.

Tumor cells adapt to excessive oxidative stress by actuating reactive oxygen species (ROS)-defensing system, leading to a resistance to oxidation therapy. In this work, self-delivery photodynamic synergists (designated as PhotoSyn) are developed for oxidative damage amplified tumor therapy. Specifically, PhotoSyn are fabricated by the self-assembly of chlorine e6 (Ce6) and TH588 through π-π stacking and hydrophobic interactions. Without additional carriers, nanoscale PhotoSyn possess an extremely high drug loading rate (up to 100%) and they are found to be fairly stable in aqueous phase with a uniform size distribution. Intravenously injected PhotoSyn prefer to accumulate at tumor sites for effective cellular uptake. More importantly, TH588-mediated MTH1 inhibition could destroy the ROS-defensing system of tumor cells by preventing the elimination of 8-oxo-2'-deoxyguanosine triphosphate (8-oxo-dG), thereby exacerbating the oxidative DNA damage induced by the photodynamic therapy (PDT) of Ce6 under light irradiation. As a consequence, PhotoSyn exhibit enhanced photo toxicity and a significant antitumor effect. This amplified oxidative damage strategy improves the PDT efficiency with a reduced side effect by increasing the lethality of ROS without generating superabundant ROS, which would provide a new insight for developing self-delivery nanoplatforms in photodynamic tumor therapy in clinic.

Mixed Solvent Method for Improving the Size Uniformity and Cargo-Loading Efficiency of ZIF-8 Nanoparticles.

Zeolitic imidazolate framework-8 (ZIF-8) nanoparticles with tunable diameters and a uniform morphology were constructed in dimethyl sulfoxide (DMSO)/H2O mixed solvents and were further decorated with dextran to improve their stability and biocompatibility. A series of reaction conditions, including the DMSO content in mixed solvents, molar ratio between precursors, growth time, and decoration of dextran, were systematically investigated. Most importantly, it was the union of DMSO and water that achieved the combined merits of both solvothermal and hydrothermal methods, namely, high uniformity and high efficiency, respectively. In addition, numerous properties of these ZIF-8 nanoparticles were subsequently studied, such as the crystal structure, surface properties, and porosity. Furthermore, composite ZIF-8 nanoparticles encapsulating various functional molecules were also successfully prepared in the same DMSO/H2O mixed solvents, thus laying the foundation for their application as nanocarriers in the biomedical field.

Self-Delivery Nanomedicine for O2-Economized Photodynamic Tumor Therapy.

Tumor hypoxia is the Achilles heel of oxygen-dependent photodynamic therapy (PDT), and tremendous challenges are confronted to reverse the tumor hypoxia. In this work, an oxidative phosphorylation inhibitor of atovaquone (ATO) and a photosensitizer of chlorine e6 (Ce6)-based self-delivery nanomedicine (designated as ACSN) were prepared via π-π stacking and hydrophobic interaction for O2-economized PDT against hypoxic tumors. Specifically, carrier-free ACSN exhibited an extremely high drug loading rate and avoided the excipient-induced systemic toxicity. Moreover, ACSN not only dramatically improved the solubility and stability of ATO and Ce6 but also enhanced the cellular internalization and intratumoral permeability. Abundant investigations confirmed that ACSN effectively suppressed the oxygen consumption to reverse the tumor hypoxia by inhibiting mitochondrial respiration. Benefiting from the synergistic mechanism, an enhanced PDT effect of ACSN was observed on the inhibition of tumor growth. This self-delivery system for oxygen-economized PDT might be a potential appealing clinical strategy for tumor eradication.

High-Order Assembly toward Polysaccharide-Based Complex Coacervate Nanodroplets Capable of Targeting Cancer Cells.

High-order assembly plays a significant role in the formation of living organisms containing a large number of biomacromolecules and, thus, enlightens the construction of nanomaterials that can load macromolecular payloads at a high efficiency. Herein, by choosing anionic hyaluronic acid (HA) as a model payload, we demonstrated how the electrostatic-interaction-induced high-order assembly can be used to load efficiently biomacromolecules into complex coacervate nanodroplets. The resultant assemblies were primarily composed of HA and cationic chitosan oligosaccharide/dextran (COS/Dex) nanogels and had a controllable structure while also exhibiting biological functionality. HA in the assemblies is capable of targeting CD44-overexpressed tumor cells through CD44-mediated endocytic pathways, which are elucidated herein. Therefore, this study provides a reliable approach for the efficient loading of macromolecular payloads into complex coacervate nanodroplets via electrostatic-attraction-induced high-order assembly.

Can virtual reality improve traditional anatomy education programmes? A mixed-methods study on the use of a 3D skull model.

BACKGROUND: Realistic, portable, and scalable lectures, cadaveric models, 2D atlases and computer simulations are being combined more frequently for teaching anatomy, which result in major increases in user satisfaction. However, although digital simulations may be more portable, interesting, or motivating than traditional teaching tools, whether they are superior in terms of student learning remain unclear. This paper presents a study in which the educational effectiveness of a virtual reality (VR) skull model is compared with that of cadaveric skulls and atlases. The aim of this study was to compare the results of teaching with VR to results of teaching with traditional teaching methods by administering objective questionnaires and perception surveys. METHODS: A mixed-methods study with 73 medical students was conducted with three different groups, namely, the VR group (N = 25), cadaver group (N = 25) and atlas group (N = 23). Anatomical structures were taught through an introductory lecture and model-based learning. All students completed the pre- and post-intervention tests, which comprised a theory test and an identification test. The theory test consisted of 18 multiple-choice questions, and the identification test consisted of 25 fill-in-the-blank questions. RESULTS: The participants in all three groups had significantly higher total scores on the post-intervention test than on the pre-intervention test; the post-intervention test score in the VR group was not statistically significantly higher than the post-intervention test score of the other groups (VR: 30 [IQR: 22-33.5], cadaver: 26 [IQR: 20-31.5], atlas: 28[IQR: 20-33]; p > 0.05). The participants in the VR and cadaver groups provided more positive feedback on their learning models than the atlas group (VR: 26 [IQR: 19-30], cadaver: 25 [IQR: 19.5-29.5], atlas: 12 [IQR: 9-20]; p < 0.001). CONCLUSIONS: The skull virtual learning resource (VLR) was equally efficient as the cadaver skull and atlas in teaching anatomy structures. Such a model can aid individuals in understanding complex anatomical structures with a higher level of motivation and tolerable adverse effects.

Case report: Transcatheter tricuspid valve intervention using K-Clip™ system after prior Kay's annuloplasty.

The K-Clip™ system is emerging as an alternative to correct tricuspid regurgitation (TR) for patients with high surgical risk. However, patients with recurrent severe tricuspid regurgitation after prior Kay's annuloplasty are not generally deemed to be candidates for K-Clip™ implantation. Herein, we report a case of a 63-year-old woman with recurrent symptomatic torrential tricuspid regurgitation 5 years after double valve replacement with Kay's annuloplasty of the tricuspid valve. The K-Clip™ was successfully implanted, and the severity of tricuspid regurgitation and dimensions of tricuspid annulus achieved significant reduction. In conclusion, K-Clip™ can still be feasible and effective for patients with prior Kay's annuloplasty. However, indications become more rigorous, and evaluation should be more comprehensive.

Pulsed field ablation as a precise approach for cardiac arrhythmia treatment via cardiac microenvironment remodeling.

PFA uses short-duration, high-voltage electrical pulses to induce transient or irreversible electroporation on cell membranes, causing cell death. Selective inhibition of chaotic electrical signals in morbid cardiomyocytes significantly aids the treatment of atrial fibrillation, ventricular tachycardia, and other heart arrhythmias. Recent preclinical and clinical studies have only investigated physical changes, such as lesion size and myocardial scar. Compared to radiofrequency ablation and cryoballoon ablation, PFA causes less postoperative myocardial cell fibrosis and inflammatory reaction and does not result in myocardial necrosis or tissue scar formation. However, the regulatory mechanism of cellular stress following PFA treatment remains unknown. This study aimed to analyze the transcriptome of the mouse ventricle after PFA treatment. The animals were subjected to a 225-V electric pulse with a 1.5-mm gap between the positive and negative electrodes. Hearts were harvested at 3, 6, 12, 24 h, and 2, 5 days for myocardial zymogram testing. PFA-treated ventricular regions were selected for single-nucleus sequencing. We discovered that PFA remodeled the cardiac microenvironment as a whole. Further, we discussed the possible stress response and wound-healing mechanism in non-targeted cells. In conclusion, PFA allowed effective and selective ventricular myocardium ablation with controllable inflammation.

Single-Cell Diagnosis of Cancer Drug Resistance through the Differential Endocytosis of Nanoparticles between Drug-Resistant and Drug-Sensitive Cancer Cells.

Single-cell diagnosis of cancer drug resistance is highly relevant for cancer treatment, as it can be used to identify the subpopulations of drug-resistant cancer cells, reveal the sensitivity of cancer cells to treatment, and monitor the progress of cancer drug resistance. However, simple and effective methods for cancer drug resistance detection at the single-cell level are still lacking in laboratory and clinical studies. Inspired by the fact that nanoparticles with diverse physicochemical properties would generate distinct and specific interactions with drug-resistant and drug-sensitive cancer cells, which have distinctive molecular signatures, here, we have synthesized a library of fluorescent nanoparticles with various sizes, surface charges, and compositions (SiO2 nanoparticles (SNPs), organic PS-co-PAA nanoparticles (ONPs), and ZIF-8 nanoparticles (ZNPs)), thus demonstrating that the composition has a critical influence on the interaction of nanoparticles with drug-resistant cancer cells. Furthermore, the clathrin/caveolae-independent endocytosis of ZNPs together with the P-glycoprotein-related decreased cell membrane fluidity resulted in a lower cellular accumulation of ZNPs in drug-resistant cancer cells, consequently causing the distinct cellular accumulation of ZNPs between the drug-resistant and drug-sensitive cancer cells. This difference was further quantified by detecting the fluorescence signals generated by the accumulation of nanoparticles at the single-cell level via flow cytometry. Our findings provide another insight into the nanoparticle-cell interactions and offer a promising platform for the diagnosis of cancer drug resistance of various cancer cells and clinical cancer samples at the single-cell level.

Monodisperse ZIF-8@dextran nanoparticles co-loaded with hydrophilic and hydrophobic functional cargos for combined near-infrared fluorescence imaging and photothermal therapy.

Impressive developments have been achieved with the use of zeolitic imidazolate framework-8 (ZIF-8) as nanocarriers for tumor theranostics in recent decades by incorporating imaging agents and therapeutic drugs within ZIF-8. However, the simultaneous immobilization of hydrophilic and hydrophobic functional molecules into ZIF-8 nanoparticles in water or organic solvents still presents a daunting challenge. Herein, we developed a new synthesis/encapsulation two-in-one (denoted as one-pot) approach to synthesize uniform dextran-modified Cy5.5&ICG@ZIF-8-Dex nanoparticles in DMSO/H2O solvent mixtures, which enabled the simultaneous encapsulation of hydrophilic indocyanine green (ICG) and hydrophobic cyanine-5.5 (Cy5.5) during the same step. It was confirmed that the one-pot approach in this mixed solvents facilitated the loading of ICG and Cy5.5 molecules. Moreover, the encapsulation of Cy5.5 and ICG within ZIF-8 nanoparticles endowed them with fluorescence imaging capability and photothermal conversion capacity, respectively. The in vivo near-infrared (NIR) fluorescent images of A549-bearing mice injected with Cy5.5&ICG@ZIF-8-Dex demonstrated sufficient accumulations of Cy5.5 at tumor sites due to the enhanced permeability and retention effect. Most impressively, the fluorescent intensity of Cy5.5&ICG@ZIF-8-Dex at tumor site was approximately 40-fold higher than that of free Cy5.5. Additionally, the results of in vivo infrared imaging and photothermal therapy of Cy5.5&ICG@ZIF-8-Dex showed enhanced therapeutic efficiency in comparison with free ICG, further confirming its tumor-targeting capability and photothermal capacity. Therefore, this multifunctional system based on ZIF-8 nanocarriers offered a potential nanoplatform for tumor-targeting theranostics, thus broadening the synthesis and applications of ZIF-8 composite nanoparticles for NIR fluorescence imaging and photothermal therapy in the biomedical field. STATEMENT OF SIGNIFICANCE: Simultaneous immobilization of hydrophilic and hydrophobic molecules into ZIF-8 nanoparticles still remains a daunting challenge. Therefore, we have developed a new synthesis/encapsulation two-in-one approach to synthesize uniform Cy5.5&ICG@ZIF-8-Dex composite nanoparticles in DMSO/H2O solvent mixtures, which enabled the simultaneous encapsulation of hydrophilic indocyanine green (ICG) and hydrophobic cyanine-5.5 (Cy5.5) functional molecules during a single step. The results showed that the co-loading of Cy5.5 and ICG within the ZIF-8 nanoparticles endowed them with a remarkable fluorescence imaging capability and photothermal conversion capacity. Based on their enhanced convenience and efficacy to simultaneously encapsulate hydrophilic and hydrophobic molecules, the multifunctional nanocarriers that were prepared in the DMSO/H2O mixed solvents provide a potential nanoplatform toward fluorescence imaging and photothermal therapy for tumor theranostics.

Multidimensional Quantitative Measurement of Cancer Chemoresistance through Differential ZIF-8 Nanoparticle Cellular Retention.

Chemoresistance of cancer cells is conventionally quantified by half-maximal inhibitory concentration (IC50) or multidrug resistance gene 1 (MDR1) values, but these metrics can only reflect the overall drug resistance level of a cancer cell line. Meanwhile, the multidimensional evaluation of both the heterogeneity in a cell line and the drug resistance degree of each cell still presents a daunting challenge. We report here that the cellular heterogeneity, cellular cross contamination, and the proportion of chemoresistant cancer cells can be visualized via flow cytometry through the differential cellular retention of fluorescent ZIF-8 nanoparticles. In addition, we show that the degree of drug resistance exhibited by each cell subpopulation can be quantified by differing fluorescence of the drug-resistant and drug-sensitive cells in the corresponding flow cytometry profile, and the quantified metric S is highly consistent with the MDR1 expression results. Importantly, this novel strategy is applicable to various cancer cell lines, thus demonstrating a universal diagnosis platform for multidimensional, quantitative, and highly efficient diagnosis of cancer chemoresistance.

Carrier free nanomedicine to reverse anti-apoptosis and elevate endoplasmic reticulum stress for enhanced photodynamic therapy.

As a first studied and generally accepted programmed cell death regulator, Bcl-2 has been identified to overexpress in many types of cancer promoting tumor proliferation and progression. Herein, inspired by drug self-delivery systems, a self-assembled nanomedicine (designated as GosCe) was designed based on the hydrophobic interaction between chlorin e6 (Ce6) and gossypol (Gos). Without extra carriers, GosCe exhibited high drug loading rates, favorable size distribution, and a long-term stability at aqueous phase. More importantly, GosCe could be internalized by tumor cells more effectively than free Ce6, which brought about its multiple toxicity. Upon intravenous injection, GosCe preferred to accumulate in tumor site through enhanced permeability and retention (EPR) effect. After cellular internalization, Gos contributed to increasing the lethality of Ce6-guided photodynamic therapy (PDT) by down-regulating Bcl-2 protein expression and inducing endoplasmic reticulum (ER) stress. Both in vitro and in vivo investigations indicated that the Gos-assisted PDT greatly inhibit cell proliferation and tumor growth. This study might shed light on developing carrier free nanomedicine for PDT-based synergistic tumor therapy. STATEMENT OF SIGNIFICANCE: Metabolic abnormalities of tumor cells create defensive microenvironments which induce a therapeutic resistance against photodynamic therapy (PDT). Among which, the upregulated B-cell lymphoma (Bcl-2) in tumors could inhibit the PDT-induced cell apoptosis. In this work, a self-delivery nanomedicine (GosCe) was developed based on a Bcl-2 inhibitor and photosensitizer through intermolecular interactions, which had favorable size distribution, high drug contents and improved drug delivery efficiency. Importantly, GosCe increased the PDT efficacy by Bcl-2 inhibition and endoplasmic reticulum stress elevation. Thus, GosCe greatly inhibited the tumor growth while caused a reduced side effect in vivo. This carrier free nanomedicine with tumor microenvironment regulation would advance the development of photodynamic nanoplatform in tumor treatment.

An innovative S-scheme AgCl/MIL-100(Fe) heterojunction for visible-light-driven degradation of sulfamethazine and mechanism insight.

The development of high efficient photocatalysts for antibiotics contamination in water remains a severe challenge. In this study, a novel step-scheme (S-scheme) photocatalytic heterojunction nanocomposites were fabricated from integrating AgCl nanoparticles on the MIL-100(Fe) octahedron surface through facile multi-stage stirring strategy. The S-scheme heterojunction structure in AgCl/MIL-100(Fe) (AM) nanocomposite provided a more rational utilization of electrons (e-) and holes (h+), accelerated the carrier transport at the junction interface, and enhanced the overall photocatalytic performance of nanomaterials. The visible-light-driven photocatalysts were used to degrade sulfamethazine (SMZ) which attained a high removal efficiency (99.9%). The reaction mechanisms of SMZ degradation in the AM photocatalytic system were explored by electron spin resonance (ESR) and active species capture experiments, which superoxide radical (•O2-), hydroxyl radical (•OH), and h+ performed as major roles. More importantly, the SMZ degradation pathway and toxicity assessment were proposed. There were four main pathways of SMZ degradation, including the processes of oxidation, hydroxylation, denitrification, and desulfonation. The toxicity of the final products in each pathway was lower than that of the parent according to the toxicity evaluation results. Therefore, this work might provide new insights into the environmentally-friendly photocatalytic processes of S-scheme AM nanocomposites for the efficient degradation of antibiotics pollutants.

A self-delivery photodynamic sensitizer for enhanced DNA damage by PARP inhibition.

Tumor cells activate DNA repair pathways to combat the oxidative damage induced by reactive oxygen species (ROS), contributing to their resistance to photodynamic therapy (PDT). Herein, a self-delivery photodynamic sensitizer is developed to enhance oxidative damage by blocking the DNA repair pathway through poly(ADP-ribose) polymerase (PARP) inhibition. Specifically, the photodynamic sensitizer (CeOla) is constructed based on the self-assembly of the photosensitizer chlorine e6 (Ce6) and the PARP inhibitor olaparib (Ola). Of note is that carrier free CeOla has a high drug content and favorable water stability, which could be effectively internalized by tumor cells for robust PDT upon light irradiation. Moreover, CeOla could inhibit the activation of PARP, promote the upregulation of γ-H2AX and reduce the expression of Rad51, thereby blocking the DNA repair pathway to sensitize tumor cells for PDT. As a consequence, the self-delivery CeOla greatly promotes the tumor cell apoptosis and shows a high antitumor performance with low side effects. It serves as a novel platform for the development of self-delivery nanomedicine to overcome oxidative resistance in tumor treatment.

Chinese SLE Treatment and Research Group Registry (CSTAR) XIV: the subjective well-being of patients with systemic lupus erythematosus.

Background: Systemic lupus erythematosus (SLE) can significantly influence patients' quality of life and subjective well-being (SWB), but the relationships between clinical characteristics, SWB, and related psychological factors have been little studied. Objective: To measure SWB in patients with SLE and examine how major clinical determinants, emotional variables, and related positive factors affect SWB. Methods: Overall, 1,110 patients with SLE from the Chinese SLE Treatment and Research Group (CSTAR) and 198 age and gender-matched individuals from the general population without self-reported SLE were invited to complete questionnaires of SWB evaluated by the satisfaction with life scale (SWLS), emotional variables assessed by the patient health questionnaire-9 (PHQ-9), and general anxiety disorder-7 (GAD-7) and related positive factors assessed by the self-esteem scale (SES), general self-efficacy scale (GESE), and Connor-Davidson resilience scale (CD-RISC). The multivariate linear regression was used to examine the relationship between clinical manifestations and SWB. Results: Life satisfaction was significantly lower (p < 0.001) in patients with SLE than in the general population. Active skin involvement (OR = 0.923, 95% CI = 0.868-0.981, p < 0.05) was negatively associated with life satisfaction scores, and age at enrollment (OR = 1.160, 95% CI = 1.092-1.230, p < 0.001) were positively associated with life satisfaction scores in the multivariate regression model. The cumulative organ damage was significantly associated with depression (OR = 1.085, 95% CI = 1.022-1.153, p < 0.01) and the loss of self-esteem (OR = 1.067, 95% CI = 1.004-1.133, p < 0.05). Conclusion: SWB provides useful insight into the impact of SLE on psychological health and opportunities to improve quality of life and clinical care.

Cell Coding Arrays Based on Fluorescent Glycan Nanoparticles for Cell Line Identification and Cell Contamination Evaluation.

Cell lines are applied on a large scale in the field of biomedicine, but they are susceptible to issues such as misidentification and cross-contamination. This situation is becoming worse over time due to the rapid growth of the biomedical field, and thus there is an urgent need for a more effective strategy to address the problem. As described herein, a cell coding method is established based on two types of uniform and stable glycan nanoparticles that are synthesized using the graft-copolymerization-induced self-assembly (GISA) method, which further exhibit distinct fluorescent properties due to elaborate modification with fluorescent labeling molecules. The different affinity between each nanoparticle and various cell lines results in clearly distinguishable differences in their endocytosis degrees, thus resulting in distinct characteristic fluorescence intensities. Through flow cytometry measurements, the specific signals of each cell sample can be recorded and turned into a map divided into different regions by statistical processing. Using this sensing array strategy, we have successfully identified six human cell lines, including one normal type and five tumor types. Moreover, cell contamination evaluation of different cell lines with HeLa cells as the contaminant in a semiquantitative analysis has also been successfully achieved. Notably, the whole process of nanoparticle fabrication and fluorescent testing is facile and the results are highly reliable.

Redox-Active Micelle-Based Reaction Platforms for In Situ Preparation of Noble Metal Nanocomposites with Photothermal Conversion Capability.

Polyferrocenylsilane (PFS)-based polymers are an attractive family of organometallic polymers with unique redox-active properties. Herein, we report a novel amphiphilic redox-active PFS-based homopolymer, poly(ferrocenylmethylethylthiocarboxypropylsilane) (PFC), with a hydrophobic backbone chain and hydrophilic carboxylic acid side groups in each repeating unit. Self-assembly was induced by addition of water to a molecularly dispersed solution of PFC in DMSO. Spherical PFC micelles with controllable hydrodynamic diameters (60-180 nm) were obtained under various conditions. These PFC micelles could be readily endocytosed by A549 cells and HUVEC cells and show no significant cytotoxicity toward them at the concentration of 200 µg/mL. On this basis, Au nanoparticles (AuNPs) were prepared through in situ reduction of HAuCl4 by PFC micelles as nanoreactors without requiring any other reductants. The PFC/Au nanocomposites (NCs) were found to exhibit significant photothermal behavior. Moreover, PFC micelles could also act as nanoreactors for other noble metals such as Ag, Pd, and Pt. By taking advantage of properties of the nanostructures and noble metal nanoparticles comprising these materials, the PFC micelles and PFC/noble metal NCs may have great potential in biomedical or catalytic applications.

Self-delivery nanomedicine for chemotherapy sensitized photodynamic therapy.

A chlorine e6 (Ce6) and curcumin (Cur) based self-delivery nanomedicine (CeCu) is prepared for chemotherapy sensitized photodynamic therapy (PDT). The chemotherapeutic agent of Cur could inhibit the TrxR activity to destroy the cellular ROS-defence system for enhanced PDT, which provides synergistic effects for tumor precision therapy in consideration of the unfavorable tumor microenvironments.

Double photoelectron-transfer mechanism in Ag-AgCl/WO3/g-C3N4 photocatalyst with enhanced visible-light photocatalytic activity for trimethoprim degradation.

Antibiotic contamination is increasing scrutinized recently. In this work, the Ag-AgCl/WO3/g-C3N4 (AWC) nanocomposites were successfully synthesized using a two-step process involving electrostatic self-assembly and in-situ deposition for trimethoprim (TMP) degradation. The as-prepared photocatalysts were investigated and characterized by XRD, FTIR, XPS, TGA, SEM, TEM, UV-vis, PL and EIS. The experimental results indicated that 99.9% of TMP (4 mg/L) was degraded within 60 min when the concentration of AWC was 0.5 g/L. Reactive species scavenging experiments and electron spin resonance (ESR) experiments illustrated that superoxide radical (•O2-) and photogenerated holes (h+) were the main active species. The functional theory calculation and identification of intermediates via HPLC-MS revealed the possible degradation pathways of TMP. A double photoelectron-transfer mechanism in AWC photocatalyst was proposed. Five cycling photocatalytic tests and reactions under different solution matrix effects further supported that the AWC was a promising photocatalyst for the removal of TMP from the aquatic environment.

Metal-coordinated nanomedicine for combined tumor therapy by inducing paraptosis and apoptosis.

Apoptosis resistance of tumor cells often results in chemoresistance and treatment failure in clinic. In this work, a Cu2+-coordinated morusin/doxorubicin biological organizer (designated as COMBO) is designed to combat cellular resistance to apoptosis for combined tumor therapy. By virtue of the coordination and π-π stacking effects, the self-assembled COMBO possesses nanometer particle size, narrow and homogenous graininess distribution as well as a good dispersion stability. Moreover, COMBO could be disassembled by glutathione (GSH) with an effective drug release and fluorescence recovery. Morusin-mediated paraptosis could induce extensive vacuolization through the dilation of endoplasmic reticulum (ER) and mitochondria, leading to non-apoptotic programmed cell death (PCD) regardless of the cellular resistance to apoptosis. Furthermore, the released doxorubicin prefers to locate in cell nucleus to cause cell apoptosis for combined chemotherapy. By the joint action of paraptosis and apoptosis, COMBO exhibits a great superiority over monotherapy in tumor inhibition with a low system toxicity. This study may open a window in the development of self-delivery nanomedicine for overcoming apoptosis resistance in tumor therapy.