Genetically Designed Living Bacteria with Melanogenesis for Tumor-Specific Pigmentation and Therapeutic Intervention.

Visual observation and therapeutic intervention against tumors hold significant appeal for tumor treatment, particularly in meeting the demands of intraoperative navigation. From a clinical perspective, the naked-eye visualization of tumors provides a direct and convenient approach to identifying tumors and navigating during surgery. Nevertheless, there is an ongoing need to develop effective solutions in this frontier. Genetically engineered microorganisms are promising as living therapeutics for combatting malignant tumors, leveraging precise tumor targeting and versatile programmed functionalities. Here, genetically modified Escherichia coli (E. coli) MG1655 bacterial cells are introduced, called MelaBac cells, designed to express tyrosinase continuously. This bioengineered melanogenesis produces melanin capable of pigmenting both subcutaneous CT26 xenografts and chemically induced colorectal cancer (CRC). Additionally, MelaBac cells demonstrate the initiation of photonic hyperthermia therapy and immunotherapy against tumors, offering promising selective therapeutic interventions with high biocompatibility.

Catechol-Isolated Atomically Dispersed Nanocatalysts for Self-Motivated Cocatalytic Tumor Therapy.

Nanocatalytic tumor therapy based on Fenton nanocatalysts has attracted considerable attention because of its therapeutic specificity, enhanced outcomes, and high biocompatibility. Nevertheless, the rate-determining step in Fenton chemistry, which involves the transition of a high-valence metallic center (FeIII ) to a Fenton-active low-valence metallic center (FeII ), has hindered advances in nanocatalyst-based therapeutics. In this study, we constructed mesoporous single iron atomic nanocatalysts (mSAFe NCs) by employing catechols from dopamine to coordinate and isolate single iron atoms. The catechols also serve as reductive ligands, generating a field-effect-based cocatalytic system that instantly reduces FeIII species to FeII species within the mSAFe NCs. This self-motivated cocatalytic strategy enabled by mSAFe NCs accelerates the kinetics of the Fenton catalytic reaction, resulting in remarkable performance for nanocatalytic tumor therapy both in vitro and in vivo.

Myocardial-Targeting Tannic Cerium Nanocatalyst Attenuates Ischemia/Reperfusion Injury.

Ischemic heart disease (IHD) is one of the leading causes of death worldwide. Medications or surgery have been considered as effective protocols to treat IHD for decades. Yet the reperfusion of the blood flow frequently leads to the generation of excessive reactive oxygen species (ROS), causing prominent and irreversible damage to the cardiomyocytes. In the present work, tannic acid-assembled tetravalent cerium (TA-Ce) nanocatalysts with appealing cardiomyocyte-targeting and antioxidation capability have been synthesized and applied for the effective and biocompatible ischemia/reperfusion injury therapeutics. TA-Ce nanocatalysts could effectively rescue the cardiomyocytes from oxidative stress induced by H2 O2 challenge as well as oxygen-glucose deprivation in vitro. In the murine ischemia/reperfusion model, cardiac accumulation and intracellular ROS scavenging could be achieved against the pathology, substantially reducing the myocardial infarct area and recovering heart functionality. This work illuminates the design of nanocatalytic metal complexes and their therapeutic prospects in ischemic heart diseases with high effectiveness and biocompatibility, paving the way for the clinical translation from bench to bedside.

Thirst in heart failure: A scoping review.

AIM: The aim of this study was to summarise the overall picture of thirst-related research in patients with heart failure. DESIGN: We conducted a scoping review following the Arskey and O'Malley methodological framework along with the PAGER framework. METHODS: PubMed, CINAHL, Web of Science, Embase, The Cochrane Library, Jonna Briggs Institute, ProQuest Database, Google Scholar, PsycINFO, PQDT, CNKI, Wan Fang, VIP and CBM. Additionally, grey literature including grey databases (Opengrey, OpenDoar, Openaire and BASEL Bielefeld Academic Search Engine), conferences or articles (Scopus and Microsoft Academic), graduate theses databases (eTHOS, DART Europe, Worldcat and EBSCO Open Dissertations) and government information media (UK guidance and regulations, USA government websites, EU Bookshop and UN official publications) were searched. The databases were searched from inception to 18 August 2022 for Articles written in English and Chinese. Two researchers independently screened articles based on inclusion and exclusion criteria, and a third researcher adjudicated disagreements. RESULTS: We retrieved 825 articles, of which 26 were included. Three themes were summarised from these articles: (a) the incidence of thirst in patients with heart failure; (b) the thirst-related factors in patients with heart failure; and (c) the intervention measures of thirst in patients with heart failure.

Genetically engineered probiotics as catalytic glucose depriver for tumor starvation therapy.

Cancer cells predominantly adapt the frequent but less efficient glycolytic process to produce ATPs rather than the highly efficient oxidative phosphorylation pathway. Such a regulated metabolic pattern in cancer cells offers promising therapeutic opportunities to kill tumors by glucose depletion or glycolysis blockade. In addition, to guarantee tumor-specific therapeutic targets, effective tumor-homing, accumulation, and retention strategies toward tumor regions should be elaborately designed. In the present work, genetically engineered tumor-targeting microbes (transgenic microorganism EcM-GDH (Escherichia coli MG1655) expressing exogenous glucose dehydrogenase (GDH) have been constructed to competitively deprive tumors of glucose nutrition for metabolic intervention and starvation therapy. Our results show that the engineered EcM-GDH can effectively deplete glucose and trigger pro-death autophagy and p53-initiated apoptosis in colorectal tumor cells/tissues both in vitro and in vivo. The present design illuminates the promising prospects for genetically engineered microbes in metabolic intervention therapeutics against malignant tumors based on catalytically nutrient deprivation, establishing an attractive probiotic therapeutic strategy with high effectiveness and biocompatibility.

Magnesium hexacyanoferrate nanocatalysts attenuate chemodrug-induced cardiotoxicity through an anti-apoptosis mechanism driven by modulation of ferrous iron.

Distressing and lethal cardiotoxicity is one of the major severe side effects of using anthracycline drugs such as doxorubicin for cancer chemotherapy. The currently available strategy to counteract these side effects relies on the administration of cardioprotective agents such as Dexrazoxane, which unfortunately has unsatisfactory efficacy and produces secondary myelosuppression. In the present work, aiming to target the characteristic ferrous iron overload in the doxorubicin-contaminated cardiac microenvironment, a biocompatible nanomedicine prepared by the polyvinylpyrrolidone-directed assembly of magnesium hexacyanoferrate nanocatalysts is designed and constructed for highly efficient intracellular ferrous ion capture and antioxidation. The synthesized magnesium hexacyanoferrate nanocatalysts display prominent superoxide radical dismutation and catalytic H2O2 decomposition activities to eliminate cytotoxic radical species. Excellent in vitro and in vivo cardioprotection from these magnesium hexacyanoferrate nanocatalysts are demonstrated, and the underlying intracellular ferrous ion traffic regulation mechanism has been explored in detail. The marked cardioprotective effect and biocompatibility render these magnesium hexacyanoferrate nanocatalysts to be highly promising and clinically transformable cardioprotective agents that can be employed during cancer treatment.

Fabry disease: Mechanism and therapeutics strategies.

Fabry disease is a monogenic disease characterized by a deficiency or loss of the α-galactosidase A (GLA). The resulting impairment in lysosomal GLA enzymatic activity leads to the pathogenic accumulation of enzymatic substrate and, consequently, the progressive appearance of clinical symptoms in target organs, including the heart, kidney, and brain. However, the mechanisms involved in Fabry disease-mediated organ damage are largely ambiguous and poorly understood, which hinders the development of therapeutic strategies for the treatment of this disorder. Although currently available clinical approaches have shown some efficiency in the treatment of Fabry disease, they all exhibit limitations that need to be overcome. In this review, we first introduce current mechanistic knowledge of Fabry disease and discuss potential therapeutic strategies for its treatment. We then systemically summarize and discuss advances in research on therapeutic approaches, including enzyme replacement therapy (ERT), gene therapy, and chaperone therapy, as well as strategies targeting subcellular compartments, such as lysosomes, the endoplasmic reticulum, and the nucleus. Finally, the future development of potential therapeutic strategies is discussed based on the results of mechanistic studies and the limitations associated with these therapeutic approaches.

Concurrent antibiosis and anti-inflammation against bacterial pneumonia by zinc hexacyanoferrate nanocatalysts.

The bacterial pneumonia has been demonstrated to cause acute and severe pathological lung injury as well as the uncontrollable oxidative cytokine storms. The effective therapeutics against bacterial pneumonia demands highly efficient pathogen elimination, oxidative stress alleviation and anti-inflammation. Nevertheless, current therapeutics fail to achieve these goals by a single medicine with satisfactory performance. Herein, we report a self-assembled zinc-doped prussian blue-analogue - zinc hexacyanoferrate nanocatalysts (ZnPBA NCs) possessing excellent broad-spectrum anti-bacterial activity and antioxidative catalytic activities against multiple reactive oxygen species (ROS) and the associated cytokine storm as well. By employing various oxidative substances and in vivo murine bacterial pneumoniae models, we verified that the synthetic zinc hexacyanoferrate nanocatalysts could concurrently eliminate the bacterial infection and largely alleviate infection-induced oxidative stress and inflammation, demonstrating the promising clinical application potentials against diverse bacterial infection-related diseases.

Probiotic Engineering and Targeted Sonoimmuno-Therapy Augmented by STING Agonist.

Tumor targeting and effective immunomodulation are of critical significance during tumor treatment by sonodynamic therapy (SDT). Herein, the probiotic engineering of the clinically approved sonosensitizer (hematoporphyrin monomethyl ether (HMME)) is reported onto the probiotic bacterium Bifidobacteria Longum (BiL) for sonosensitive bifidobacterium construction (HMME@BiL cells). Based on the hypoxic tropism feature of the strain, effective tumor-targeted sonodynamic therapeutics can be achieved both in vitro and in vivo. To improve the immunological responses against tumor during sonodynamics, a recently-developed stimulator of interferon genes immune agonist SR717 has been employed to improve the anti-tumor immunity with prominent activities, eradicating both primary and metastatic tumors with high efficiency and satisfied biocompatibility. The present work provides a promising paradigm of microbiotic nanomedicine in a sophisticated sonoimmunotherapeutic strategy against malignant tumors.

Nanozymes-recent development and biomedical applications.

Nanozyme is a series of nanomaterials with enzyme-mimetic activities that can proceed with the catalytic reactions of natural enzymes. In the field of biomedicine, nanozymes are capturing tremendous attention due to their high stability and low cost. Enzyme-mimetic activities of nanozymes can be regulated by multiple factors, such as the chemical state of metal ion, pH, hydrogen peroxide (H2O2), and glutathione (GSH) level, presenting great promise for biomedical applications. Over the past decade, multi-functional nanozymes have been developed for various biomedical applications. To promote the understandings of nanozymes and the development of novel and multifunctional nanozymes, we herein provide a comprehensive review of the nanozymes and their applications in the biomedical field. Nanozymes with versatile enzyme-like properties are briefly overviewed, and their mechanism and application are discussed to provide understandings for future research. Finally, underlying challenges and prospects of nanozymes in the biomedical frontier are discussed in this review.

Effect of crosstalk among conspirators in tumor microenvironment on niche metastasis of gastric cancer.

In Traditional Chinese medicine, the metaphoric views of the human body are based on observations of nature guided by the theory of "Yin-Yang". The direct meanings of yin and yang are the bright and dark sides of an object, which often represent a wider range of opposite properties. When we shifted our view to gastric cancer (GC), we found that there are more distinctive Yin and Yang features in the mechanism of GC development and metastasis, which is observed in many mechanisms such as GC metastasis, immune escape, and stem cell homing. When illustrating this process from the yin-yang perspective, categorizing different cells in the tumor microenvironment enables new and different perspectives to be put forward on the mechanism and treatment of GC metastasis.

Nanoprotection Against Retinal Pigment Epithelium Degeneration via Ferroptosis Inhibition.

Lethal oxidative stress and ferrous ion accumulation-mediated degeneration/death in retinal pigment epithelium (RPE) exert an indispensable impact on retinal degenerative diseases with irreversible visual impairment, especially in age-related macular degeneration (AMD), but corresponding pathogenesis-oriented medical intervention remains controversial. In this study, the potent iron-binding nanoscale Prussian blue analogue KCa[FeIII (CN)6 ] (CaPB) with high biocompatibility is designed to inhibit RPE death and subsequently photoreceptor cell degeneration. In mice, CaPB effectively prevents RPE degeneration and ultimately fulfills superior therapeutic outcomes upon a single intravitreal injection: significant rescue of retinal structures and visual function. Through high-throughput RNA sequencing and sophisticated biochemistry evaluations, the findings initially unveil that CaPB nanoparticles protect against RPE degradation by inhibiting ferroptotic cell fate. Together with the facile, large-scale preparations and in vivo biosafety, it is believed that the synthesized CaPB therapeutic nanoparticles are promising for future clinical treatment of diverse retinal diseases involving pathological iron-dependent ferroptosis, including AMD.

Targeting Ferroptosis by Polydopamine Nanoparticles Protects Heart against Ischemia/Reperfusion Injury.

Ferroptosis is a new form of regulated cell death depending on elevated iron (Fe2+) and lipid peroxidation levels. Myocardial ischemia/reperfusion (I/R) injury has been shown to be closely associated with ferroptosis. Therefore, antiferroptosis agents are considered to be a new strategy for managing myocardial I/R injury. Here, we developed polydopamine nanoparticles (PDA NPs) as a new type of ferroptosis inhibitor for cardioprotection. The PDA NPs features intriguing properties in inhibiting Fe2+ accumulation and restoring mitochondrial functions in H9c2 cells. Subsequently, we demonstrated that administration of PDA NPs effectively reduced Fe2+ deposition and lipid peroxidation in a myocardial I/R injury mouse model. In addition, the myocardial I/R injury in mice was alleviated by PDA NPs treatment, as demonstrated by reduced infarct size and improved cardiac functions. The present work indicates the therapeutic effects of PDA NPs against myocardial I/R injury via preventing ferroptosis.

NIR -I and NIR-II irradiation tumor ablation using NbS2 nanosheets as the photothermal agent.

Photothermal therapy has been considered a powerful means of cancer therapy due to its minimal invasiveness, effectiveness, and convenience. Although promising, the therapeutic effects are greatly limited as they rely on the photothermal agent (PTA). It is urgent to develop new PTAs with high photothermal conversion performance, especially under irradiation in the long-wavelength biowindows. Herein, a dual-biowindow-responsive PTA made of NbS2-PVP nanosheets was fabricated to be used both in the first near-infrared (NIR-I) and the second near-infrared (NIR-II) biowindows. With excellent hydrophilicity and biocompatibility, the nanosheets could effectively convert the near-infrared (NIR) light into heat, showing prominent photothermal stability. The calculated photothermal conversion efficiencies reached 59.2% (under NIR-I excitation) and 69.1% (under NIR-II excitation), respectively, which are comparable to those of metallic PTAs. The NbS2-PVP nanosheets had low cytotoxicity and could trigger strong photothermal treatment and cause cancer cell death upon irradiation by NIR-I or NIR-II light in vitro. Moreover, we have also demonstrated the highly efficient tissue ablation and tumor inhibition capability of NbS2-PVP nanosheets in vivo. This work explores an effective PTA of two-dimensional nanomaterials in NIR-I and NIR-II biowindows and offers a reference for the design of new kinds of PTAs.

Ischemic Microenvironment-Responsive Therapeutics for Cardiovascular Diseases.

Cardiovascular diseases caused by ischemia are attracting considerable attention owing to its high morbidity and mortality worldwide. Although numerous agents with cardioprotective benefits have been identified, their clinical outcomes are hampered by their low bioavailability, poor drug solubility, and systemic adverse effects. Advances in nanoscience and nanotechnology provide a new opportunity to effectively deliver drugs for treating ischemia-related diseases. In particular, cardiac ischemia leads to a characteristic pathological environment called an ischemic microenvironment (IME), significantly different from typical cardiac regions. These remarkable differences between ischemic sites and normal tissues have inspired the development of stimuli-responsive systems for the targeted delivery of therapeutic drugs to damaged cardiomyocytes. Recently, many biomaterials with intelligent properties have been developed to enhance the therapeutic benefits of drugs for the treatment of myocardial ischemia. Strategies for stimuli-responsive drug delivery and release based on IME include reactive oxygen species, pH-, hypoxia-, matrix metalloproteinase-, and platelet-inspired targeting strategies. In this review, state-of-the-art IME-responsive biomaterials for the treatment of myocardial ischemia are summarized. Perspectives, limitations, and challenges are also discussed for the further development of innovative and effective approaches to treat ischemic diseases with high effectiveness and biocompatibility.

Photosynthetic Cyanobacteria-Hybridized Black Phosphorus Nanosheets for Enhanced Tumor Photodynamic Therapy.

Photodynamic therapy (PDT) has attracted tremendous attention due to its advantages such as high safety and effectiveness compared to traditional radiotherapy and chemotherapy. However, the intratumoral hypoxic microenvironment will inevitably compromise the PDT effect of the highly oxygen-dependent type II photosensitizers, implicating the urgent demand for continuous intratumoral oxygenation. Herein, biocompatible photosynthetic cyanobacteria have been modified with inorganic two-dimensional black phosphorus nanosheets (BPNSs) to be a novel bioreactor termed as Cyan@BPNSs. Upon 660 nm laser irradiation, the photosynthetic cyanobacteria generate oxygen continuously in situ through photosynthesis, followed by the photosensitization of BPNSs for activating oxygen into singlet oxygen (1 O2 ), resulting in a large amount of 1 O2 accumulation at the tumor site and the consequent strong tumor cell killing effect both in vitro and in vivo. This work provides an attractive strategy for efficient and biocompatible PDT, meanwhile extends the scope of microbiotic nanomedicine by hybridizing microorganisms with inorganic nanophotosensitizer.

Engineering Single-Atomic Iron-Catalyst-Integrated 3D-Printed Bioscaffolds for Osteosarcoma Destruction with Antibacterial and Bone Defect Regeneration Bioactivity.

Effective antitumor therapeutics with distinctive bactericidal and osteogenic properties are in high demand for comprehensive osteosarcoma treatment. Here, a "scaffold engineering" strategy that integrates highly active single-atomic iron catalysts (FeSAC) into a 3D printed bioactive glass (BG) scaffold is reported. Based on the atomically dispersed iron species within the catalysts, the engineered FeSAC displays prominent Fenton catalytic activity to generate toxic hydroxyl radicals (•OH) in response to the microenvironment specific to osteosarcoma. In addition, the constructed FeSAC-BG scaffold can serve as a sophisticated biomaterial platform for efficient osteosarcoma ablation, with concomitant bacterial sterilization via localized hyperthermia-reinforced nanocatalytic therapeutics. The destruction of the osteosarcoma, as well as the bacterial foci, can be achieved, further preventing susceptible chronic osteomyelitis during osteogenesis. In particular, the engineered FeSAC-BG scaffold is identified with advances in accelerated osteoconduction and osteoinduction, ultimately contributing to the sophisticated therapeutics and management of osteosarcoma. This work broadens the biomedical potential of single-atom catalysts and offers a comprehensive clinically feasible strategy for overall osteosarcoma therapeutics, bacterial inhibition, and tissue regeneration.

Autophagy blockade synergistically enhances nanosonosensitizer-enabled sonodynamic cancer nanotherapeutics.

Ultrasound-triggered sonodynamic therapy (SDT) represents an emerging therapeutic modality for cancer treatment based on its specific feature of noninvasiveness, high tissue-penetrating depth and desirable therapeutic efficacy, but the SDT-induced pro-survival cancer-cell autophagy would significantly lower the SDT efficacy for cancer treatment. Here we propose an "all-in-one" combined tumor-therapeutic strategy by integrating nanosonosensitizers-augmented noninvasive SDT with autophagy inhibition based on the rationally constructed nanoliposomes that co-encapsulates clinically approved sonosensitizers protoporphyrin IX (PpIX) and early-phase autophagy-blocking agent 3-methyladenine (3-MA). It has been systematically demonstrated that nanosonosensitizers-augmented SDT induced cytoprotective pro-survival autophagy through activation of MAPK signaling pathway and inhibition of AMPK signaling pathway, and this could be efficaciously inhibited by 3-MA in early-phase autophagy, which significantly decreased the cell resistance to intracellular oxidative stress and complied a remarkable synergistic effect on SDT medicated cancer-cell apoptosis both in vitro at cellular level and in vivo on tumor-bearing animal model. Therefore, our results provide a proof-of-concept combinatorial tumor therapeutics based on nanosonosensitizers for the treatment of ROS-resistant cancer by autophagy inhibition-augmented SDT.

Photonic hyperthermal and sonodynamic nanotherapy targeting oral squamous cell carcinoma.

Nanomedicine that enables multiple synergetic treatments provides effective non-invasive treatment modalities for cancer therapy. Yet treatments for oral squamous cell carcinoma (OSCC) are rarely reported. Here, we designed OSCC-targeting multi-functional nanomedicines to overcome the therapeutic obstacles during OSCC treatments, including ineffective chemotherapy, and the traumatic surgery and radiotherapy. The urokinase plasminogen activator receptor (uPAR)-targeting ligand AE105 decorated dendritic mesoporous silica nanoparticles (DMSN) encapsulating photonic active ultrasmall Cu2-xS NPs and sonosensitizer Rose Bengal (RB) have been rationally designed and constructed (designated as Cu2-xS-RB@DMSN-AE105, abbreviated as CRDA). These CRDAs initially target the uPAR, which is overexpressed in the OSCC cell membrane, to increase the localized accumulation of CRDAs at tumor sites. Under the irradiation of both near-infrared laser and ultrasound, the in situ photonic-hyperthermal and sonodynamic effects are respectively enabled to induce the cell death of OSCC. Upon both in vitro/in vivo challenges, tumor cells/xenografts have been efficiently eradicated, achieving the targeting and synergetic treatment modality against the OSCC with satisfactory biocompatibility.

Photosynthetic Tumor Oxygenation by Photosensitizer-Containing Cyanobacteria for Enhanced Photodynamic Therapy.

Sustained tumor oxygenation is of critical importance during type-II photodynamic therapy (PDT), which depends on the intratumoral oxygen level for the generation of reactive oxygen species. Herein, the modification of photosynthetic cyanobacteria with the photosensitizer chlorin e6 (ce6) to form ce6-integrated photosensitive cells, termed ceCyan, is reported. Upon 660 nm laser irradiation, sustained photosynthetic O2 evolution by the cyanobacteria and the immediate generation of reactive singlet oxygen species (1 O2 ) by the integrated photosensitizer could be almost simultaneously achieved for tumor therapy using type-II PDT both in vitro and in vivo. This work contributes a conceptual while practical paradigm for biocompatible and effective PDT using hybrid microorganisms, displaying a bright future in clinical PDT by microbiotic nanomedicine.