Bimetallic nanoreactor mediates cascade amplification of oxidative stress for complementary chemodynamic-immunotherapy of tumor.

As a promising tumor treatment, chemodynamic therapy (CDT) can specifically catalyze HO into the cytotoxic hydroxyl radical (·OH) via Fenton/Fenton-like reaction. However, the limited HO and weakly acidic pH in tumor microenvironment (TME) would severely restrict the therapeutic efficiency of CDT. Here, a weakly acid activated, HO self-supplied, hyaluronic acid (HA)-functionalized Ce/Cu bimetallic nanoreactor (CBPNs@HA) is elaborately designed for complementary chemodynamic-immunotherapy.

Lactate/Cysteine Dual-Consuming Probiotic-Nanomedicine Biohybrid System for Enhanced Cancer Chemo-Immunotherapy.

Immunotherapy is revolutionizing oncology, but its therapeutic efficiency is still limited by the off-target toxicities and poor antitumor immune responses. By integrating the drug-loaded nanoparticles (DMnSH) with the unique metabolic traits of (Vei), a probiotic-nanomedicine conjugate Vei@DMnSH biohybrid is elaborately designed for enhanced cancer chemo-immunotherapy. Specifically, Vei@DMnSH can accumulate in hypoxic tumor sites and simultaneously consume lactate and cysteine to reverse the lactate-associated immunosuppression and impede the biosynthesis of GSH.

Harnessing the Engineered Probiotic-Nanosystem to Remodulate Tumor Extracellular Matrix and Regulate Tumor-Colonizing Bacteria for Improving Pancreatic Cancer Chemo-Immunotherapy.

Poor chemotherapy efficacy in pancreatic cancer is attributed to limited drug permeation caused by the dense extracellular matrix (ECM) and drug degradation induced by tumor-colonizing bacteria. Here, a tumor-targeting probiotic-nanosystem is elaborately designed to remodulate ECM and selectively regulate tumor-colonizing bacteria for improving chemo-immunotherapy against pancreatic cancer. Specifically, drug-loaded liposomes are conjugated with Clostridium Butyricum (CB) via matrix metalloproteinase-2 (MMP-2)-responsive peptide to construct a probiotic-nanosystem.

Targeted Elimination of the Oral Pathogen to Overcome Chemoresistance of Oral Squamous Cell Carcinoma by Biologically Derived Nanotherapeutics.

Local oral microbiota are closely related to the tumorigenesis and therapeutic response of oral cancer. In this study, we have validated that oral commensal () is highly responsible for chemoresistance and contributes to the poor therapeutic outcome of traditional chemotherapy. Accordingly, the biologically derived nanovesicles from ginger (GDNVs) with excellent elimination ability are explored to transport the clinically used drug paclitaxel (PTX) for potentiating the therapeutic efficiency.

Engineered bacterium-metal-organic framework biohybrids for boosting radiotherapy with multiple effects.

Hypoxia and lactate-overexpressed tumor microenvironment always lead to poor therapeutic effect of radiotherapy. Here, platinum nanoparticles-embellished hafnium metal-organic framework (Hf-MOF-Pt NPs) were elaborately integrated with Shewanella oneidensis MR-1 (SO) to construct an engineered biohybrid platform (SO@Hf-MOF-Pt) for enhancing radiotherapy. Benefiting from the tumor-targeting and metabolic respiration characteristics of SO, SO@Hf-MOF-Pt could enrich in tumor sites and continuously metabolize the overexpressed lactate, which specifically downregulated the expression of hypoxia-inducible factor (HIF-1α), thereby relieving the radiosuppressive tumor microenvironment to some extent.

Interference of ATP-Adenosine Axis by Engineered Biohybrid for Amplifying Immunogenic Cell Death-Mediated Antitumor Immunotherapy.

Immunogenic cell death (ICD) often results in the production and accumulation of adenosine (ADO), a byproduct that negatively impacts the therapeutic effect as well as facilitates tumor development and metastasis. Here, an innovative strategy is elaborately developed to effectively activate ICD while avoiding the generation of immunosuppressive adenosine. Specifically, ZIF-90, an ATP-responsive consumer, is synthesized as the core carrier to encapsulate AB680 (CD73 inhibitor) and then coated with an iron-polyphenol layer to prepare the ICD inducer (AZTF), which is further grafted onto prebiotic bacteria via the esterification reaction to obtain the engineered biohybrid (Bc@AZTF).

Immunostimulant Hydrogel-Guided Tumor Microenvironment Reprogramming to Efficiently Potentiate Macrophage-Mediated Cellular Phagocytosis for Systemic Cancer Immunotherapy.

Macrophage-mediated cellular phagocytosis (MMCP) plays a critical role in conducting antitumor immunotherapy but is usually impaired by the intrinsic phagocytosis evading ability of tumor cells and the immunosuppressive tumor microenvironment (TME). Herein, a MMCP-boosting hydrogel (TCCaGM) was elaborately engineered by encapsulating granulocyte-macrophage colony-stimulating factor (GM-CSF) and a therapeutic nanoplatform (TCCaN) that preloaded with the tunicamycin (Tuni) and catalase (CAT) with the assistance of CaCO nanoparticles (NPs). Strikingly, the hypoxic/acidic TME was efficiently alleviated by the engineered hydrogel, "eat me" signal calreticulin (CRT) was upregulated, while the "don't eat me" signal CD47 was downregulated on tumor cells, and the infiltrated DCs were recruited and activated, all of which contributed to boosting the macrophage-mediated phagocytosis and initiating tumor-specific CD8 T cells responses.

Fused Cytomembrane-Camouflaged Nanoparticles for Tumor-Specific Immunotherapy.

Tumor immunotherapy is commonly hindered by inefficient delivery and presentation of tumor antigens as well as immunosuppressive tumor microenvironment. To overcome these barriers, a tumor-specific nanovaccine capable of delivering tumor antigens and adjuvants to antigen-presenting cells and modulating the immune microenvironment to elicit strong antitumor immunity is reported. This nanovaccine, named FCM@4RM, is designed by coating the nanocore (FCM) with a bioreconstituted cytomembrane (4RM).

Specific activation of cGAS-STING pathway by nanotherapeutics-mediated ferroptosis evoked endogenous signaling for boosting systemic tumor immunotherapy.

Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway could effectively initiate antitumor immunity, but specific activation of STING pathway is still an enormous challenge. Herein, a ferroptosis-induced mitochondrial DNA (mtDNA)-guided tumor immunotherapy nanoplatform (designated as HBMn-FA) was elaborately developed for activating and boosting STING-based immunotherapy. On the one hand, the high-levels of reactive oxygen species (ROS) in tumor cells induced by HBMn-FA-mediated ferroptosis elicited mitochondrial stress to cause the release of endogenous signaling mtDNA, which specifically initiate cGAS-STING pathway with the cooperation of Mn.

Interference of Glucose Bioavailability of Tumor by Engineered Biohybrids for Potentiating Targeting and Uptake of Antitumor Nanodrugs.

The chemotherapy efficacy of nanodrugs is restricted by poor tumor targeting and uptake. Here, an engineered biohybrid living material (designated as EcN@HPB) is constructed by integrating paclitaxel and BAY-876 bound human serum albumin nanodrugs (HPB) with Nissle 1917 (EcN). Due to the inherent tumor tropism of EcN, EcN@HPB could actively target the tumor site and competitively deprive glucose through bacterial respiration.

Essential thrombocythemia with non-ST-segment elevation myocardial infarction as the first manifestation: A case report.

Background: We report a case of essential thrombocythemia (ET) in a 44-year-old male who exhibited non-ST-segment-elevation myocardial infarction (NSTEMI) as the first manifestation without known cardiovascular risk factors (CVRFs). For the first time, we reported a left main trifurcation lesion in NSTEMI caused by ET, including continuous stenosis lesions from the left main to the ostial left anterior descending (LAD) artery and an obvious thrombotic lesion in the ostial and proximal left circumflex (LCX) artery. There was 60% diffuse stenosis in the left main (LM) that extended to the ostial LAD, thrombosis of the ostial LAD and proximal LCX, and 90% stenosis in the proximal LCX.

Biomedical polymers: synthesis, properties, and applications.

Biomedical polymers have been extensively developed for promising applications in a lot of biomedical fields, such as therapeutic medicine delivery, disease detection and diagnosis, biosensing, regenerative medicine, and disease treatment. In this review, we summarize the most recent advances in the synthesis and application of biomedical polymers, and discuss the comprehensive understanding of their property-function relationship for corresponding biomedical applications. In particular, a few burgeoning bioactive polymers, such as peptide/biomembrane/microorganism/cell-based biomedical polymers, are also introduced and highlighted as the emerging biomaterials for cancer precision therapy.

A Self-Driven Bioreactor Based on Bacterium-Metal-Organic Framework Biohybrids for Boosting Chemotherapy Cyclic Lactate Catabolism.

The excessive lactate in the tumor microenvironment always leads to poor therapeutic outcomes of chemotherapy. In this study, a self-driven bioreactor (defined as SO@MDH, where SO is MR-1 and MDH is MIL-101 metal-organic framework nanoparticles/doxorubicin/hyaluronic acid) is rationally constructed the integration of doxorubicin (DOX)-loaded metal-organic framework (MOF) MIL-101 nanoparticles with SO to sensitize chemotherapy. Owing to the intrinsic tumor tropism and electron-driven respiration of SO, the biohybrid SO@MDH could actively target and colonize hypoxic and eutrophic tumor regions and anaerobically metabolize lactate accompanied by the transfer of electrons to Fe, which is the key component of the MIL-101 nanoparticles.

A tumor-cell biomimetic nanoplatform embedding biological enzymes for enhanced metabolic therapy.

A tumor cell membrane-camouflaged therapeutic system was fabricated to eliminate tumors by embedding apyrase and glucose oxidase (GOx) into zeolitic imidazolate framework-8 (ZIF-8) nanoparticles for tumor-targeted metabolic therapy. Experimental results demonstrated that these functional nanoparticles could disturb the energy supply of tumor cells by depleting ATP and glucose and efficiently induce tumor cell death.

Recent Advances in Engineered Materials for Immunotherapy-Involved Combination Cancer Therapy.

Immunotherapy that can activate immunity or enhance the immunogenicity of tumors has emerged as one of the most effective methods for cancer therapy. Nevertheless, single-mode immunotherapy is still confronted with several critical challenges, such as the low immune response, the low tumor infiltration, and the complex immunosuppression tumor microenvironment. Recently, the combination of immunotherapy with other therapeutic modalities has emerged as a powerful strategy to augment the therapeutic outcome in fighting against cancer.

Mechatronics design and testing of a cable-driven upper limb rehabilitation exoskeleton with variable stiffness.

In this paper, we present a cable-driven exoskeleton with variable stiffness for upper limb rehabilitation. Adjustable stiffness of the cable-driven exoskeleton is achieved by attaching a novel variable stiffness module (VSM) to each driving cable. The module is able to vary stiffness in a large range through changing cable tension.

Cell primitive-based biomimetic functional materials for enhanced cancer therapy.

Cell primitive-based functional materials that combine the advantages of natural substances and nanotechnology have emerged as attractive therapeutic agents for cancer therapy. Cell primitives are characterized by distinctive biological functions, such as long-term circulation, tumor specific targeting, immune modulation etc. Moreover, synthetic nanomaterials featuring unique physical/chemical properties have been widely used as effective drug delivery vehicles or anticancer agents to treat cancer.

100th Anniversary of Macromolecular Science Viewpoint: Poly(-isopropylacrylamide)-Based Thermally Responsive Micelles.

Poly(-isopropylacrylamide) (PNIPAAm)-based thermally responsive micelles are of great importance as smart materials for a number of applications such as drug delivery and biosensing, owing to their tunable lower critical solution temperature (LCST). Their design and synthesis in the nanoscale size range have been widely studied, and research interest in their structural and physic-chemical properties is continually growing. In this Viewpoint, representative research on the construction of PNIPAAm-based thermally responsive micelles as well as their applications are highlighted and discussed, which would serve as a good start for newcomers in this field and a positive guide for future research.

Modelling Photosynthesis with Zn -Protoporphyrin All-DNA G-Quadruplex/Aptamer Scaffolds.

All-DNA scaffolds act as templates for the organization of photosystem I model systems. A series of DNA templates composed of Zn -protoporphyrin IX (Zn PPIX)-functionalized G-quadruplex conjugated to the 3'- or 5'-end of the tyrosinamide (TA) aptamer and Zn PPIX/G-quadruplex linked to the 3'- and 5'-ends of the TA aptamer through a four-thymidine bridge. Effective photoinduced electron transfer (ET) from Zn PPIX/G-quadruplex to bipyridinium-functionalized tyrosinamide, TA-MV , bound to the TA aptamer units is demonstrated.

MicroRNA-Guided Selective Release of Loads from Micro-/Nanocarriers Using Auxiliary Constitutional Dynamic Networks.

Two different drug micro-carriers consisting of doxorubicin-dextran (DOX-D)- and camptothecin-modified carboxymethyl cellulose (CPT-CMC)-loaded nucleic acid-stabilized microcapsules, MC-1 and MC-2, or two different nanocarriers consisting of nucleic-acid-locked doxorubicin (DOX)- and camptothecin (CPT)-loaded metal-organic framework nanoparticles, NMOF-1 and NMOF-2, are coupled to auxiliary constitutional dynamic networks, CDNs, for the triggered release of the drugs. CDN "S" composed of four constituents AA'', AB', BA', and BB', and two hairpin structures, H and H, leads to the CDN "S"-guided unlocking of the MC-1/MC-2 carriers and the release of DOX-D and CPT-CMC or of the NMOF-1 and NMOF-2 carriers that release DOX and CPT, respectively. The unlocking processes are activated by the cleavage of H and H by BB' and BA', respectively, to yield fragmented strands that unlock the gating units of the microcapsules/NMOFs carriers.

An adaptive stair-ascending gait generation approach based on depth camera for lower limb exoskeleton.

The mobility on stairways is a daily challenge for seniors and people with dyskinesia. Lower limb exoskeletons can be effective assistants to improve their life quality. In this paper, we present an adaptive stair-ascending gait generation algorithm based on a depth camera for lower limb exoskeletons.

Thrombin Aptamer-Modified Metal-Organic Framework Nanoparticles: Functional Nanostructures for Sensing Thrombin and the Triggered Controlled Release of Anti-Blood Clotting Drugs.

This paper features the synthesis of thrombin-responsive, nucleic acid-gated, UiO-68 metal-organic framework nanoparticles (NMOFs) loaded with the drug Apixaban or rhodamine 6G as a drug model. Apixaban acts as an inhibitor of blood clots formation. The loads in the NMOFs are locked by duplex nucleic acids that are composed of anchor nucleic acids linked to the NMOFs that are hybridized with the anti-thrombin aptamer.

Photosensitized H Evolution and NADPH Formation by Photosensitizer/Carbon Nitride Hybrid Nanoparticles.

The broadband CN semiconductor absorbs in the UV region, λ = 330-380 nm, a feature limiting its application for light-to-energy conversion. The unique surface adsorption properties of CN allow, however, the binding of a photosensitizer, operating in the visible-solar spectrum to the surface of CN. Coupling of the energy levels of the photosensitizer with the energy levels of CN allows effective photoinduced electron-transfer quenching and subsequent charge separation in the hybrid structures.

Knee exoskeleton enhanced with artificial intelligence to provide assistance-as-needed.

Robotic therapy is a useful method applied during rehabilitation of stroke patients (to regain motor functions). To ensure active participation of the patient, assistance-as-needed is provided during robotic training. However, most existing studies are based on a predetermined desired trajectory, which significantly limits the use of this method for more complex scenarios.