Human natural killer cells for targeting delivery of gold nanostars and bimodal imaging directed photothermal/photodynamic therapy and immunotherapy

Objective:To construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars(GNSs)with Chlorin e6 molecules(Ce6)into human peripheral blood mononuclear cells(PBMCs)-derived NK cells for tumor targeted therapy.Methods:GNS@CaCO3/Ce6 nanoparticles were prepared and characterized by TEM and UV-vis.The cell surface markers and cytokines secretion of NK cells before and after loading the GNS@CaCO3/Ce6 nanoparticles were detected by Flow Cytometry(FCM)and ELISA.Effects of the GNS@CaCO3/Ce6-NK cells on A549 cancer cells was determined by FCM and CCK-8.Intracellular fluorescent signals of GNS@CaCO3/Ce6-NK cells were detected via Confocal laser scanning microscopic(CLSM)and FCM at different time points.Intracellular ROS generation of GNS@CaCO3/Ce6-NK cells under laser irradiation were examined by FCM.The distribution of GNS@CaCO3/Ce6-NK in A549 tumor-bearing mice were observed by fluorescence imaging and PA imaging.The combination therapy of GNS@CaCO3/Ce6-NK under laser irradiation were investigated on tumor-bearing mice.Results:The coated CaC03 shell on the surface of GNSs exhibited prominent delivery and protection effect of Ce6 during the cellular uptake process.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells possessed bimodal functions of fluorescence imaging and photoacoustic imaging.The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells could actively target tumor tissues with the enhanced photothermal/photodynamic therapy and immunotherapy.Conclusions:The GNS@CaCO3/Ce6-NK shows effective tumor-targeting ability and prominent therapeutic efficacy toward lung cancer A549 tumor-bearing mice.Through fully utilizing the features of GNSs and NK cells,this new nanoplatform provides a new synergistic strategy for enhanced photothermal/photodynamic therapy and immunotherapy in the field of anticancer development in the near future.

A Review on Metal-and Metal Oxide-Based Nanozymes:Properties,Mechanisms,and Applications

Since the ferromagnetic(Fe_(3)O_(4))nanoparticles were firstly reported to exert enzyme-like activity in 2007,extensive research progress in nanozymes has been made with deep investigation of diverse nanozymes and rapid development of related nanotechnologies.As promising alterna-tives for natural enzymes,nanozymes have broadened the way toward clinical medicine,food safety,environmental monitoring,and chemical production.The past decade has witnessed the rapid development of metal-and metal oxide-based nanozymes owing to their remarkable physicochemical proper-ties in parallel with low cost,high stability,and easy storage.It is widely known that the deep study of catalytic activities and mechanism sheds sig-nificant influence on the applications of nanozymes.This review digs into the characteristics and intrinsic properties of metal-and metal oxide-based nanozymes,especially emphasizing their catalytic mechanism and recent applications in biological analysis,relieving inflammation,antibacterial,and cancer therapy.We also conclude the present challenges and provide insights into the future research of nanozymes constituted of metal and metal oxide nanomaterials.

Advances in isolation and detection of circulating tumor cells based on microfluidics

Circulating tumor cells(CTCs) are the cancer cells that circulate in the peripheral blood after escaping from the original or metastatic tumors. CTCs could be used as non-invasive source of clinical information in early diagnosis of cancer and evaluation of cancer development. In recent years, CTC research has become a hotspot field wherein many novel CTC detection technologies based on microfluidics have been developed. Great advances have been made that exhibit obvious technical advantages, but cannot yet satisfy the current clinical requirements. In this study, we review the main advances in isolation and detection methods of CTC based on microfluidics research over several years, propose five technical indicators for evaluating these methods, and explore the application prospects. We also discuss the concepts, issues, approaches, advantages, limitations, and challenges with an aim of stimulating a broader interest in developing microfluidics-based CTC detection technology.

N-doped coaxial CNTs@a-Fe_2O_3@C nanofibers as anode material for high performance lithium ion battery

N-doped coaxial CNTs@α-Fe_2O_3@C nanofibers have been successfully synthesized according to a facile solvothermal/hydrothermal method. The obtained CNTs@α-Fe_2O_3@C nanofibers composites exhibited spe- cial three-dimensional （3-D） network structure, which endows they promising candidate for anode ma- terials of lithium ion battery. The coaxial property of CNTs@α-Fe_2O_3@C nanofibers could significantly improve the cycling and rate performance owing to the acceleration of charge/electron transfer, improve- ment of conductivity, maintaining of structural integrity and inhibiting the aggregation. The α-Fe_2O_3 nanoparticles with small size and high percentage of N-doped amount could further improve the elec- trochemical performance. As for the CNTs@α-Fe_2O_3@C nanofibers, the capacity presented a high value of 1255.4 mAh/g at 0.1 C, and retained at 1213.4 mAh/g after 60 cycles. Even at high rate of 5 C, the ca- pacity still exhibited as high as 319 mAh/g. The results indicated that the synthesized N-doped coaxial CNTs@α-Fe_2O_3@C nanofibers exhibited high cvcling and rate oerformance.

Human iPS Cells Loaded with MnO2-Based Nanoprobes for Photodynamic and Simultaneous Enhanced Immunotherapy Against Cancer

How to trigger strong anti-tumor immune responses has become a focus for tumor therapy.Here,we report the human-induced pluripotent stem cells(iPSs)to deliver MnO2@Ce6 nanoprobes into tumors for simultaneous photodynamic therapy(PDT)and enhanced immunotherapy.Ce6 photosensitizer was attached on manganese dioxide(MnO2)nanoparticles,and resultant MnO2@Ce6 nanoprobes were delivered into mitomycin-treated iPSs to form iPS-MnO2@Ce6 nanoprobes.The iPS-MnO2@Ce6 actively targeted in vivo tumors,the acidic microenvironment triggered interaction between MnO2 and H2O2,released large quantities of oxygen,alleviated hypoxia in tumor.Upon PDT,singlet oxygen formed,broken iPSs released tumor-shared antigens,which evoked an intensive innate and adaptive immune response against the tumor,improving dendritic cells matured,effector T cells,and natural killer cells were activated.Meanwhile,regulatory T cells were reduced,and then the immune response induced by iPS-MnO2@Ce6 was markedly stronger than the immune reaction induced by MnO2@Ce6(P<0.05).The iPS-MnO2@Ce6 markedly inhibited tumor growth and metastasis and reduced mortality in mice models with tumor.Human iPS s loaded with MnO2-based nanoprobes are a promising strategy for simultaneous PDT and enhanced immunotherapy against tumor and own clinical translational prospect.

Human induced pluripotent stem cells labeled with fluorescent magnetic nanoparticles for targeted imaging and hyperthermia therapy for gastric cancer

Objective: Human induced pluripotent stem(i PS) cells exhibit great potential for generating functional human cells for medical therapies. In this paper, we report for use of human i PS cells labeled with fluorescent magnetic nanoparticles(FMNPs) for targeted imaging and synergistic therapy of gastric cancer cells in vivo. Methods: Human i PS cells were prepared and cultured for 72 h. The culture medium was collected, and then was coincubated with MGC803 cells. Cell viability was analyzed by the MTT method. FMNP-labeled human i PS cells were prepared and injected into gastric cancer-bearing nude mice. The mouse model was observed using a small-animal imaging system. The nude mice were irradiated under an external alternating magnetic field and evaluated using an infrared thermal mapping instrument. Tumor sizes were measured weekly. Results: iP S cells and the collected culture medium inhibited the growth of MGC803 cells. FMNP-labeled human iP S cells targeted and imaged gastric cancer cells in vivo, as well as inhibited cancer growth in vivo through the external magnetic field. Conclusion: FMNP-labeled human i PS cells exhibit considerable potential in applications such as targeted dual-mode imaging and synergistic therapy for early gastric cancer.

Dual-targeted lung cancer therapy via inhalation delivery of UCNP-siRNA-AS1411 nanocages

Objective:Although great progress has been made in the field of siRNA gene therapy,safe,efficient,and targeted delivery of siRNA are still major challenges in siRNA therapeutics.Methods:We developed an up-conversion nanoparticle-based nanocage system.This system protected the siRNA from being degraded by nucleases in organisms and selectively delivered the siRNAs to the tumor sites,due to modifications of targeted molecules on the surfaces of nanocages and local inhalation.Results:The siRNAs delivered by the up-conversion nanoparticle nanocages were protected from degradation in transit to the tumor sites,where they accumulated.Compared with the passive target and control groups,the up-conversion nanoparticles based on the nanocage system showed a tumor suppressive effect after approximately 3 weeks of treatment.Conclusions:The up-conversion nanoparticle nanocages efficiently delivered vascular endothelial growth factor siRNAs to tumor sites.Mice with lung tumors treated with tumors targeting up-conversion nanoparticle nanocages showed steady body weight changes,high tumor inhibition ratios,and longer survival times.

Cell Nanomechanics Based on Dielectric Elastomer Actuator Device

As a frontier of biology,mechanobiology plays an important role in tissue and biomedical engineering.It is a common sense that mechanical cues under extracellular microenvironment affect a lot in regulating the behaviors of cells such as proliferation and gene expression,etc.In such an interdisciplinary field,engineering methods like the pneumatic and motor-driven devices have been employed for years.Nevertheless,such techniques usually rely on complex structures,which cost much but not so easy to control.Dielectric elastomer actuators(DEAs)are well known as a kind of soft actuation technology,and their research prospect in biomechanical field is gradually concerned due to their properties just like large deformation(>100%)and fast response(<1 ms).In addition,DEAs are usually optically transparent and can be fabricated into small volume,which make them easy to cooperate with regular microscope to realize real-time dynamic imaging of cells.This paper first reviews the basic components,principle,and evaluation of DEAs and then overview some corresponding applications of DEAs for cellular mechanobiology research.We also provide a comparison between DEA-based bioreactors and current custom-built devices and share some opinions about their potential applications in the future according to widely reported results via other methods.

表征不同DNA高阶结构的单分子方法

DNA不仅是生命遗传信息的载体,而且是一种高度可编程和自组装的纳米材料。不同的DNA结构与其生物和化学功能有关。因此,了解各种DNA结构的物理和化学性质在生物学和纳米化学中具有重要意义。然而,批量分析忽略了溶液中DNA结构的异质性。单分子方法是观察单个分子行为和探测自由能态高度非均质性的有力工具。在本文中,介绍了单分子方法,包括单分子检测和操作方法,并讨论了这些方法如何有助于测量单链/双链DNA(ss/dsDNA)、DNA高阶结构和DNA纳米结构的分子性质。本文为DNA纳米技术与单分子方法的结合提供了一个新的视角,以了解DNA和其他生物物质和软物质的生物物理特性。

Photothermally Enhanced Dual Enzyme-mimic Activity of Gold-Palladium Hybrid Nanozyme for Cancer Therapy

Based on characteristics of the tumor microenvironment(TME),including acidity,hypoxia,inflammation and hydrogen peroxide overload,combined with emerging nanotechnologies,designing nanoplatforms with TME specificity/responsiveness for tumor treatment is a promising nanotherapeutic strategy.In this work,a multifunctional gold-palladium bimetallic cascade nanozyme was constructed for effective photothermal-enhanced cascade catalyzed synergistic therapy of tumors.The dumbbell-like Au-Pd bimetallic nanomaterial(Au NRs-Pd@HA)was obtained by reducing palladium on gold nanorods with ascorbic acid(AA)and further modified with hyaluronic acid(HA).The introduction of HA brings biocompatibility and targeting properties.The zebrafish embryos model showed that Au NRs-Pd@HA had good biocompatibility and low biotoxicity.Au NRs-Pd@HA can induce catalytic conversion of glucose to generate H_(2)O_(2) efficiently,and subsequently undergo cascade reaction to produce abundant·OH radicals,exhibiting peroxidase-like(POD-like)and glucose oxidase-like(GOD-like)capabilities.The generated·OH was a key factor for tumor ablation.Meanwhile,Au NRs-Pd@HA exhibits good photothermal performance under 808 nm irradiation,in favor of photothermal therapy(PTT).Especially,the POD-like and GOD-like activities were significantly enhanced due to the photothermal effect.The synergistic PTT and photothermal-enhanced nanozymes with cascade catalytic effect enabled efficient and safe cancer therapy.

Microglia in neurodegenerative diseases

A major feature of neurodegeneration is disruption of central nervous system homeostasis,during which microglia play diverse roles.In the central nervous system,microglia serve as the first line of immune defense and function in synapse pruning,injury repair,homeostasis maintenance,and regulation of brain development through scavenging and phagocytosis.Under pathological conditions or various stimulations,microglia proliferate,aggregate,and undergo a variety of changes in cell morphology,immunophenotype,and function.This review presents the features of microglia,especially their diversity and ability to change dynamically,and reinterprets their role as sensors for multiple stimulations and as effectors for brain aging and neurodegeneration.This review also summarizes some therapeutic approaches for neurodegenerative diseases that target microglia.

The updated landscape of tumor microenvironment and drug repurposing

Accumulating evidence shows that cellular and acellular components in tumor microenvironment(TME)can reprogram tumor initiation,growth,invasion,metastasis,and response to therapies.Cancer research and treatment have switched from a cancercentric model to a TME-centric one,considering the increasing significance of TME in cancer biology.Nonetheless,the clinical efficacy of therapeutic strategies targeting TME,especially the specific cells or pathways of TME,remains unsatisfactory.Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly benefit further studies exploring effective treating methods.Herein,we present an updated image of TME with emphasis on hypoxic niche,immune microenvironment,metabolism microenvironment,acidic niche,innervated niche,and mechanical microenvironment.We then summarize conventional drugs including aspirin,celecoxib,β-adrenergic antagonist,metformin,and statin in new antitumor application.These drugs are considered as viable candidates for combination therapy due to their antitumor activity and extensive use in clinical practice.We also provide our outlook on directions and potential applications of TME theory.This review depicts a comprehensive and vivid landscape of TME from biology to treatment.

Gold nanoprisms as a hybrid in vivo cancer theranostic platform for in situ photoacoustic imaging, angiography, and localized hyperthermia

The development of high-resolution nanosized photoacoustic contrast agents is an exciting yet challenging technological advance. Herein, antibody （breast cancer-associated antigen I （Brcaal） monoclonal antibody）- and peptide （RGD）- functionalized gold nanoprisms （AuNprs） were used as a combinatorial methodology for in situ photoacoustic imaging, angiography, and localized hyperthermia using orthotopic and subcutaneous murine gastric carcinoma models. RGD-conjugated PEGylated AuNprs are available for tumor angiography, and Brcaal monodonal antibody-conjugated PEGylated AuNprs are used for targeting and for in situ imaging of gastric carcinoma in orthotopic tumor models. In situ photoacoustic imaging allowed for anatomical and functional imaging at the tumor site. In vivo tumor angiography imaging showed enhancement of the photoacoustic signal in a time-dependent manner. Furthermore, photoacoustic imaging demonstrated that tumor vessels were clearly damaged after localized hyperthermia. This is the first proof-of-concept using two AuNprs probes as highly sensitive contrasts and therapeutic agents for in situ tumor detection and inhibition. These smart antibody/peptide AuNprs can be used as an efficient nanotheranostic platform for in vivo tumor detection with high sensitivity, as well as for tumor targeting therapy which, with a single-dose injection, results in tumor size reduction and increases mice survival after localized hyperthermia treatment.

C60 Fullerenes Suppress Reactive Oxygen Species Toxicity Damage in Boar Sperm

We report the carboxylated C60 improved the survival and quality of boar sperm during liquid storage at 4°C and thus propose the use of carboxylated C60 as a novel antioxidant semen extender supplement.Our results demonstrated that the sperm treated with 2μg mL?1 carboxylated C60 had higher motility than the control group(58.6%and 35.4%,respectively;P?0.05).Moreover,after incubation with carboxylated C60 for 10 days,acrosome integrity and mitochondrial activity of sperm increased by 18.1%and 34%,respectively,compared with that in the control group.Similarly,the antioxidation abilities and adenosine triphosphate levels in boar sperm treated with carboxylated C60 significantly increased(P?0.05)compared with those in the control group.The presence of carboxylated C60 in semen extender increases sperm motility probably by suppressing reactive oxygen species(ROS)toxicity damage.Interestingly,carboxylated C60 could protect boar sperm from oxidative stress and energy deficiency by inhibiting the ROS-induced protein dephosphorylation via the cAMP-PKA signaling pathway.In addition,the safety of carboxylated C60 as an alternative antioxidant was also comprehensively evaluated by assessing the mean litter size and number of live offspring in the carboxylated C60 treatment group.Our findings confirm carboxylated C60 as a novel antioxidant agent and suggest its use as a semen extender supplement for assisted reproductive technology in domestic animals.

Hydrothermal synthesis of ultrathin hexagonal nickel hydroxide nanosheets

Nickel hydroxide, Ni（OH）2 is widely used in electrodes of nickel-based alkaline secondary batteries, Ultrathin hexagonal Ni（OH）2 nanosheets of space group P-3ml were hydrothermally prepared at 200℃ for 10h. Their diameter and thickness were 200-300 and 3-5 nm, respectively, Their formation was attributed to the oriented assembly of growing particles, which was assisted by surfactant molecules. The specific surface area of the Ni（OH）2 nanosheets was 8.66 m2/g. Their magnetization curve exhibited linear paramagnetic behavior across the entire measurement region.

Potassium sodium tartrate-assisted hydrothermal synthesis of BaLuFs ：Yb3＋/Er3＋ nanocrystals

Highly-dispersed BaLuFs：yb3＋/Er3＋ nanocrystals were prepared by a facile potassium sodium tartrate- assisted hydrothermal method. The average particle size was approximately 20-25 nm. The formation mechanism is discussed. Potassium sodium tartrate led to form a complex with an approximately three- dimensional network structure, which insured largely concurrent nucleation. As a result, we acquired uniform nanoparticles. The hydrothermal temperature, holding time, and pH value were important fac- tors affecting the formation of the BaLuF5 ：yb3＋/Er3＋ nanocrystals. We investigated their influence on the formation and realized the optimal reaction parameters. Remarkably, potassium sodium tartrate also con- tributed to the biocompatibility and potential biomedical applications of BaLuFs ：Yb3＋/Er3＋ nanocrystals by decomposing into small organic groups attached to the nanoparticles.

Application of near-infrared fluorescence imaging in theranostics of gastrointestinal tumors

Gastrointestinal cancers have become an important cause of cancer-related death in humans.Improving the early diagnosis rate of gastrointestinal tumors and improving the effect of surgical treatment can significantly improve the survival rate of patients.The conventional diagnostic method is high-definition white-light endoscopy,which often leads to missed diagnosis.For surgical treatment,intraoperative tumor localization and post-operative anastomotic state evaluation play important roles in the effect of surgical treatment.As a new imaging method,near-infrared fluorescence imaging(NIRFI)has its unique advantages in the diagnosis and auxiliary surgical treatment of gastrointestinal tumors due to its high sensitivity and the ability to image deep tissues.In this review,we focus on the latest advances of NIRFI technology applied in early diagnosis of gastrointestinal tumors,identification of tumor margins,identification of lymph nodes,and assessment of anastomotic leakage.In addition,we summarize the advances of NIRFI systems such as macro imaging and micro imaging systems,and also clearly describe the application process of NIRFI from system to clinical application,and look into the prospect of NIRFI applied in the theranostics of gastrointestinal tumors.

Artificial intelligence in theranostics of gastric cancer, a review

Gastric cancer (GC) is one of the commonestcancers with high morbidity and mortality in the world.How to realize precise diagnosis and therapy of GC ownsgreat clinical requirement. In recent years, artificial intelligence (AI) has been actively explored to apply to earlydiagnosis and treatment and prognosis of gastric carcinoma. Herein, we review recent advance of AI in earlyscreening, diagnosis, therapy and prognosis of stomachcarcinoma. Especially AI combined with breath screeningearly GC system improved 97.4 % of early GC diagnosisratio, AI model on stomach cancer diagnosis system of salivabiomarkers obtained an overall accuracy of 97.18 %, speci-ficity of 97.44 %, and sensitivity of 96.88 %. We also discussconcept, issues, approaches and challenges of AI applied instomach cancer. This review provides a comprehensive viewand roadmap for readers working in this field, with the aimof pushing application of AI in theranostics of stomachcancer to increase the early discovery ratio and curativeratio of GC patients.

GSH-triggered sequential catalysis for tumor imaging and eradication based on star-like Au/Pt enzyme carrier system

Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment.In this regard,we have successfully prepared a sequential catalytic platform based on Au/Pt star for tumor theragnostic.The multifunctional probes consisted of a gold/platinum star-shaped core(Au/Pt star)conjugated with a GSH-sensitive disulfide bond(S–S),a targeting ligand(rHSA-FA),a near-infrared fluorophore(IR780)and glucose oxidase(GOx).When systemically administered in a xenografted murine model,the probes specifically targeted the tumor sites.As the disulfide linker was cleaved by intracellular GSH,the IR780 molecules could be released for photo-thermal therapy&photodynamic therapy(PTT&PDT)and imaging.Subsequently,the Pt nanolayer of the Au/Pt star and the GOx formed a sequential catalytic system:GOx effectively catalyzed intracellular glucose by consuming oxygen to generate H2O2 and enhance the local acidity,and the Pt layer exhibited peroxidase-like property to catalyze H2O2 producing toxic·OH for tumor oxidative damage.Here we demonstrated that our probes simultaneously possessed a GSH-sensitive release,real-time imaging ability,and synergetic cancer starving-like therapy/enzyme oxidative therapy/PTT/PDT features,which provides a potential strategy for effective tumor theragnostic.

Efficient photocatalysis triggered by thin carbon layers coating on photocatalysts:recent progress and future perspectives

Solar-energy-driven photocatalysis,such as photocatalytic reduction of CO2,is promising simultaneously for the energy and environmental issues.Coating thin carbon layers with the thickness less than 10 nm on photocatalysts has been developed as an efficient strategy for enhancing the photocatalytic efficiency in recent years.In the present review,we summarize the crucial progress on carbon-coated photocatalysts.Origins for the improved light absorption,charge separation,reactant adsorption and photocatalytic stability on carbon-coated photocatalysts as well as the applications of carbon-coated photocatalysts are discussed.Future opportunities and challenges associated with carbon-coated photocatalysts are shown at the end of the review.We hope that the present review can trigger more deep insights on carbon-coated photocatalysts and provide new opportunities for developing low-cost but efficient photocatalysts.