Expanded ROS Generation and Hypoxia Reversal: Excipient-free Self-assembled Nanotheranostics for Enhanced Cancer Photodynamic Immunotherapy.

The efficacy of photodynamic therapy (PDT)-related cancer therapies is significantly restricted by two irreconcilable obstacles, i.e., low reactive oxygen species (ROS) generation capability and hypoxia which constrains the immune response. Herein, this work develops a self-assembled clinical photosensitizer indocyanine green (ICG) and the HSP90 inhibitor 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) nanoparticles (ISDN) without any excipient. This work discovers that the hydrophobic interaction forces between ICG and 17-DMAG promote the photostability of ICG and its intersystem crossing (ISC) process, thereby improving the ROS quantum yield from 0.112 to 0.46. Augmented ROS generation enhances PDT efficacy and further enhances immunogenic cell death (ICD) effects. 17-DMAG inhibits the HSP90/hypoxia-inducible factor 1α (HIF-1α) axis to dramatically reverse the immunosuppressive tumor microenvironment caused by PDT-aggravated hypoxia. In a mouse model of pancreatic cancer, ISDN markedly improve cytotoxic T lymphocyte infiltration and MHC I and MHC II activation, demonstrating the superior ICD effects in situ tumor and the powerful systematic antitumor immunity generation, eventually achieving vigorous antitumor and recurrence resistance. This study proposes an unsophisticated and versatile strategy to significantly improve PDT efficacy for enhancing systemic antitumor immunity and potentially extending it to multiple cancers.

Hybrid Membrane-Coated Nanoparticles for Precise Targeting and Synergistic Therapy in Alzheimer's Disease.

The blood brain barrier (BBB) limits the application of most therapeutic drugs for neurological diseases (NDs). Hybrid cell membrane-coated nanoparticles derived from different cell types can mimic the surface properties and functionalities of the source cells, further enhancing their targeting precision and therapeutic efficacy. Neuroinflammation has been increasingly recognized as a critical factor in the pathogenesis of various NDs, especially Alzheimer's disease (AD). In this study, a novel cell membrane coating is designed by hybridizing the membrane from platelets and chemokine (C-C motif) receptor 2 (CCR2) cells are overexpressed to cross the BBB and target neuroinflammatory lesions. Past unsuccessful endeavors in AD drug development underscore the challenge of achieving favorable outcomes when utilizing single-mechanism drugs.Two drugs with different mechanisms of actions into liposomes are successfully loaded to realize multitargeting treatment. In a transgenic mouse model for familial AD (5xFAD), the administration of these drug-loaded hybrid cell membrane liposomes results in a significant reduction in amyloid plaque deposition, neuroinflammation, and cognitive impairments. Collectively, the hybrid cell membrane-coated nanomaterials offer new opportunities for precise drug delivery and disease-specific targeting, which represent a versatile platform for targeted therapy in AD.

Supramolecular Lipid Nanoparticles Based on Host-Guest Recognition: A New Generation Delivery System of mRNA Vaccines For Cancer Immunotherapy.

Dendritic cell (DC) maturation is a crucial process for antigen presentation and the initiation of T cell-mediated immune responses. Toll-like receptors play pivotal roles in stimulating DC maturation and promoting antigen presentation. Here, a novel message RNA (mRNA) cancer vaccine is reported that boosts antitumor efficacy by codelivering an mRNA encoding tumor antigen and a TLR7/8 agonist (R848) to DC using supramolecular lipid nanoparticles (SMLNP) as a delivery platform, in which a new ionizable lipid (N2-3L) remarkably enhances the translation efficiency of mRNA and a ß-cyclodextrin (ß-CD)-modified ionizable lipid (Lip-CD) encapsulates R848. The incorporation of R848 adjuvant into the mRNA vaccine through noncovalent host-guest complexation significantly promotes DC maturation and antigen presentation after vaccination, thus resulting in superior antitumor efficacy in vivo. Moreover, the antitumor efficacy is further boosted synergized with immune checkpoint blockade by potentiating the anticancer capability of cytotoxic T lymphocytes infiltrated in tumor sites. This work indicates that SMLNP shows brilliant potential as next-generation delivery system in the development of mRNA vaccines with high efficacy.

Self-adaptive pyroptosis-responsive nanoliposomes block pyroptosis in autoimmune inflammatory diseases.

Nanoliposomes have a broad range of applications in the treatment of autoimmune inflammatory diseases because of their ability to considerably enhance drug transport. For their clinical application, nanoliposomes must be able to realize on-demand release of drugs at disease sites to maximize drug-delivery efficacy and minimize side effects. Therefore, responsive drug-release strategies for inflammation treatment have been explored; however, no specific design has been realized for a responsive drug-delivery system based on pyroptosis-related inflammation. Herein, we report a pioneering strategy for self-adaptive pyroptosis-responsive liposomes (R8-cardiolipin-containing nanoliposomes encapsulating dimethyl fumarate, RC-NL@DMF) that precisely release encapsulated anti-pyroptotic drugs into pyroptotic cells. The activated key pyroptotic protein, the N-terminal domain of gasdermin E, selectively integrates with the cardiolipin of liposomes, thus forming pores for controlled drug release, pyroptosis, and inflammation inhibition. Therefore, RC-NL@DMF exhibited effective therapeutic efficacies to alleviate autoimmune inflammatory damages in zymosan-induced arthritis mice and dextran sulfate sodium-induced inflammatory bowel disease mice. Our novel approach holds great promise for self-adaptive pyroptosis-responsive on-demand drug delivery, suppressing pyroptosis and treating autoimmune inflammatory diseases.

PBA-Derived Heteroatom-Doped Mesoporous Graphitic Spheroids as Peroxidase Nanozyme for In Vitro Tumor Cells Detection.

Inspired by the two kinds of naturally occurring peroxidases (POD) with vanadium or heme (iron)-based active catalytic centers, we have developed a dual metal-based nanozyme with dual V and Fe-based active catalytic centers. Co-doping of graphene with heteroatoms has a synergistic effect on the catalytic properties of the nanomaterial as the distances of migration of the substrates drastically reduce. However, a few studies have reported the codoping of heterometallic elements in the graphene structure due to the complexity of the synthesis procedures. Herein, we report the synthesis of in situ doped bimetallic VNFe@C mesoporous graphitic spheroids nanozyme via pyrolysis without the assistance of any template assisted method. The Prussian-blue analog-based precursor material was synthesized by a facile one-step low-temperature synthesis procedure. The bimetallic spheroids showed an excellent affinity toward H2O2, with a Km value of 0.26 mM when compared to 0.436 for the natural POD, which is much better than the natural POD, which was utilized to detect tumor cells in vitro through the intracellular H2O2 produced by these cells under high oxidative stress. The VNFe@C mesoporous spheroids generate dual reactive oxygen species, including the •OH and •O2H- radicals, in the presence of H2O2, which are responsible for the POD-like activity of these nanozymes, while the bimetallic V/Fe doping plays a synergistic role in the enhancement of the activity of codoped graphitic spheroids.

Lyophilized lymph nodes for improved delivery of chimeric antigen receptor T cells.

Lymph nodes are crucial organs of the adaptive immune system, orchestrating T cell priming, activation and tolerance. T cell activity and function are highly regulated by lymph nodes, which have a unique structure harbouring distinct cells that work together to detect and respond to pathogen-derived antigens. Here we show that implanted patient-derived freeze-dried lymph nodes loaded with chimeric antigen receptor T cells improve delivery to solid tumours and inhibit tumour recurrence after surgery. Chimeric antigen receptor T cells can be effectively loaded into lyophilized lymph nodes, whose unaltered meshwork and cytokine and chemokine contents promote chimeric antigen receptor T cell viability and activation. In mouse models of cell-line-derived human cervical cancer and patient-derived pancreatic cancer, delivery of chimeric antigen receptor T cells targeting mesothelin via the freeze-dried lymph nodes is more effective in preventing tumour recurrence when compared to hydrogels containing T-cell-supporting cytokines. This tissue-mediated cell delivery strategy holds promise for controlled release of various cells and therapeutics with long-term activity and augmented function.

Dual-Responsive Supramolecular Polymeric Nanomedicine for Self-Cascade Amplified Cancer Immunotherapy.

Insufficient tumor immunogenicity and immune escape from tumors remain common problems in all tumor immunotherapies. Recent studies have shown that pyroptosis, a form of programmed cell death that is accompanied by immune checkpoint inhibitors, can induce effective immunogenic cell death and long-term immune activation. Therapeutic strategies to jointly induce pyroptosis and reverse immunosuppressive tumor microenvironments are promising for cancer immunotherapy. In this regard, a dual-responsive supramolecular polymeric nanomedicine (NCSNPs) to self-cascade amplify the benefits of cancer immunotherapy is designed. The NCSNPs are formulated by ß-cyclodextrin coupling nitric oxide (NO) donor, a pyroptosis activator, and NLG919, an indoleamine 2,3-dioxygenase (IDO) inhibitor, and self-assembled through host-guest molecular recognition and hydrophobic interaction to obtain nanoparticles. NCSNPs possess excellent tumor accumulation and bioavailability attributed to ingenious supramolecular engineering. The study not only confirms the occurrence of NO-triggered pyroptosis in tumors for the first time but also reverses the immunosuppressive microenvironment in tumor sites via an IDO inhibitor by enhancing the infiltration of cytotoxic T lymphocytes, to achieve remarkable inhibition of tumor proliferation. Thus, this study provides a novel strategy for cancer immunotherapy.

Engineered Luminescent Oncolytic Vaccinia Virus Activation of Photodynamic-Immune Combination Therapy for Colorectal Cancer.

Oncolytic virus therapy is currently regarded as a promising approach in cancer immunotherapy. It has greater therapeutic advantages for colorectal cancer that is prone to distant metastasis. However, the therapeutic efficacy and clinical application of viral agents alone for colorectal cancer remain suboptimal. In this study, an engineered oncolytic vaccinia virus (OVV-Luc) that expresses the firefly luciferase gene is developed and loaded Chlorin e6 (Ce6) onto the virus surface through covalent coupling, resulting in OVV-Luc@Ce6 (OV@C). The OV@C infiltrates tumor tissue and induces endogenous luminescence through substrate catalysis, resulting in the production of reactive oxygen species. This unique system eliminates the need for an external light source, making it suitable for photodynamic therapy (PDT) in deep tissues. Moreover, this synergistic effect between PDT and viral immunotherapy enhances dendritic cell maturation, macrophage polarization, and reversal of the immunosuppressive microenvironment. This synergistic effect has the potential to convert a "cold" into a "hot" tumor, it offers valuable insights for clinical translation and application.

Fructose-1,6-bisphosphatase 1 dephosphorylates and inhibits TERT for tumor suppression.

Telomere dysfunction is intricately linked to the aging process and stands out as a prominent cancer hallmark. Here we demonstrate that telomerase activity is differentially regulated in cancer and normal cells depending on the expression status of fructose-1,6-bisphosphatase 1 (FBP1). In FBP1-expressing cells, FBP1 directly interacts with and dephosphorylates telomerase reverse transcriptase (TERT) at Ser227. Dephosphorylated TERT fails to translocate into the nucleus, leading to the inhibition of telomerase activity, reduction in telomere lengths, enhanced senescence and suppressed tumor cell proliferation and growth in mice. Lipid nanoparticle-mediated delivery of FBP1 mRNA inhibits liver tumor growth. Additionally, FBP1 expression levels inversely correlate with TERT pSer227 levels in renal and hepatocellular carcinoma specimens and with poor prognosis of the patients. These findings demonstrate that FBP1 governs cell immortality through its protein phosphatase activity and uncover a unique telomerase regulation in tumor cells attributed to the downregulation or deficiency of FBP1 expression.

ATP-Responsive Manganese-Based Bacterial Materials Synergistically Activate the cGAS-STING Pathway for Tumor Immunotherapy.

Stimulating the cyclic guanosine monophophate(GMP)-adenosine monophosphate (AMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway is a crucial strategy by which bacteria activate the tumor immune system. However, the limited stimulation capability poses significant challenges in advancing bacterial immunotherapy. Here, an adenosine 5'-triphosphate (ATP)-responsive manganese (Mn)-based bacterial material (E. coli@PDMC-PEG (polyethylene glycol)) is engineered successfully, which exhibits an exceptional ability to synergistically activate the cGAS-STING pathway. In the tumor microenvironment, which is characterized by elevated ATP levels, this biohybrid material degrades, resulting in the release of divalent manganese ions (Mn2+ ) and subsequent bacteria exposure. This combination synergistically activates the cGAS-STING pathway, as Mn2+ enhances the sensitivity of cGAS to the extracellular DNA (eDNA) secreted by the bacteria. The results of the in vivo experiments demonstrate that the biohybrid materials E. coli@PDMC-PEG and VNP20009@PDMC-PEG effectively inhibit the growth of subcutaneous melanoma in mice and in situ liver cancer in rabbits. Valuable insights for the development of bacteria-based tumor immunotherapy are provided here.

Macrophages as targets in hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is a malignant tumor with a complex and diverse immunosuppressive microenvironment. Tumor-associated macrophages (TAMs) are an essential component of the tumor immune microenvironment. TAMs typically exist in two primary states: anti-tumor M1 macrophages and pro-tumor M2 macrophages. Remarkably, TAMs possess high plasticity, enabling them to switch between different subtypes or alter their biological functions in response to the tumor microenvironment. Based on research into the biological role of TAMs in the occurrence and development of malignant tumors, including HCC, TAMs are emerging as promising targets for novel tumor treatment strategies. In this review, we provide a detailed introduction to the origin and subtypes of TAMs, elucidate their interactions with other cells in the complex tumor microenvironment of HCC, and describe the biological roles, characteristics, and mechanisms of TAMs in the progression of HCC. Furthermore, we furnish an overview of the latest therapeutic strategies targeting TAMs.

Inflammation-Responsive Cell Membrane-Camouflaged Nanoparticles against Liver Fibrosis via Regulating Endoplasmic Reticulum Stress and Oxidative Stress.

Liver fibrosis represents a reversible stage of various chronic liver diseases that progresses to cirrhosis. This condition is characterized by an imbalance between tissue damage and repair, and the production of fibers in the liver exceeds their degradation. Oxidative stress (OS) resulting from tissue injury and endoplasmic reticulum stress (ERS) triggered by the overproduction of proteins are pivotal factors in liver fibrosis. Melatonin demonstrates the capability to neutralize free radicals, shielding cells from oxidative harm. It is also a specific inhibitor of the ERS receptor transcription activating factor 6 (ATF6), indicating its great potential in ameliorating liver fibrosis. However, its limited water solubility and oral bioavailability of under 15% present hurdles in achieving therapeutic blood concentrations for treating liver fibrosis. The PLGA@Melatonin is constructed by loading melatonin with poly (lactic-co-glycolic acid) (PLGA). Platelet membranes (PM) and activated hepatic stellate cell membranes (HSCM) with high expression of the platelet-derived growth factor receptor (PDGFR) are extracted to successfully construct PM@PLGA@Melatonin and HSCM@PLGA@Melatonin, which are subsequently utilized to treat mice with liver fibrosis. The results illustrated the remarkable therapeutic effects of the two nanoparticles on liver fibrosis, along with their excellent targeting and biosafety properties.

Endothelial YAP/TEAD1-CXCL17 signaling recruits myeloid-derived suppressor cells against liver ischemia-reperfusion injury.

BACKGROUND AND AIMS: Liver ischemia-reperfusion injury (IRI) is a common complication of liver transplantation and hepatectomy and causes acute liver dysfunction and even organ failure. Myeloid-derived suppressor cells (MDSCs) accumulate and play immunosuppressive function in cancers and inflammation. However, the role of MDSCs in liver IRI has not been defined. APPROACH AND RESULTS: We enrolled recipients receiving OLT and obtained the pre-OLT/post-OLT blood and liver samples. The proportions of MDSCs were significantly elevated after OLT and negatively associated with liver damage. In single-cell RNA-sequencing analysis of liver samples during OLT, 2 cell clusters with MDSC-like phenotypes were identified and showed maturation and infiltration in post-OLT livers. In the mouse model, liver IRI mobilized MDSCs and promoted their infiltration in the damaged liver, and intrahepatic MDSCs were possessed with enhanced immunosuppressive function by upregulation of STAT3 signaling. Under treatment with αGr-1 antibody or adoptive transfer MDSCs to change the proportion of MDSCs in vivo, we found that intrahepatic MDSCs alleviated liver IRI-induced inflammation and damage by inhibiting M1 macrophage polarization. Mechanistically, bulk RNA-sequencing analysis and in vivo experiments verified that C-X-C motif chemokine ligand 17 (CXCL17) was upregulated by YAP/TEAD1 signaling and subsequently recruited MDSCs through binding with GPR35 during liver IRI. Moreover, hepatic endothelial cells were the major cells responsible for CXCL17 expression in injured livers, among which hypoxia-reoxygenation stimulation activated the YAP/TEAD1 complex to promote CXCL17 transcription. CONCLUSIONS: Endothelial YAP/TEAD1-CXCL17 signaling recruited MDSCs to attenuate liver IRI, providing evidence of therapeutic potential for managing IRI in liver surgery.

Advancing nanotechnology for neoantigen-based cancer theranostics.

Neoantigens play a pivotal role in the field of tumour therapy, encompassing the stimulation of anti-tumour immune response and the enhancement of tumour targeting capability. Nonetheless, numerous factors directly influence the effectiveness of neoantigens in bolstering anti-tumour immune responses, including neoantigen quantity and specificity, uptake rates by antigen-presenting cells (APCs), residence duration within the tumour microenvironment (TME), and their ability to facilitate the maturation of APCs for immune response activation. Nanotechnology assumes a significant role in several aspects, including facilitating neoantigen release, promoting neoantigen delivery to antigen-presenting cells, augmenting neoantigen uptake by dendritic cells, shielding neoantigens from protease degradation, and optimizing interactions between neoantigens and the immune system. Consequently, the development of nanotechnology synergistically enhances the efficacy of neoantigens in cancer theranostics. In this review, we provide an overview of neoantigen sources, the mechanisms of neoantigen-induced immune responses, and the evolution of precision neoantigen-based nanomedicine. This encompasses various therapeutic modalities, such as neoantigen-based immunotherapy, phototherapy, radiotherapy, chemotherapy, chemodynamic therapy, and other strategies tailored to augment precision in cancer therapeutics. We also discuss the current challenges and prospects in the application of neoantigen-based precision nanomedicine, aiming to expedite its clinical translation.

Ultra-stable threose nucleic acid-based biosensors for rapid and sensitive nucleic acid detection and in vivo imaging.

The human genome's nucleotide sequence variation, such as single nucleotide mutations, can cause numerous genetic diseases. However, detecting nucleic acids accurately and rapidly in complex biological samples remains a major challenge. While natural deoxyribonucleic acid (DNA) has been used as biorecognition probes, it has limitations like poor specificity, reproducibility, nuclease-induced enzymatic degradation, and reduced bioactivity on solid surfaces. To address these issues, we introduce a stable and reliable biosensor called graphene oxide (GO)- threose nucleic acid (TNA). It comprises chemically modified TNA capture probes on GO for detecting and imaging target nucleic acids in vitro and in vivo, distinguishing single nucleobase mismatches, and monitoring dynamic changes in target microRNA (miRNA). By loading TNA capture probes onto the GO substrate, the GO-TNA sensing platform for nucleic acid detection demonstrates a significant 88-fold improvement in the detection limit compared to TNA probes alone. This platform offers a straightforward preparation method without the need for costly and labor-intensive isolation procedures or complex chemical reactions, enabling real-time analysis. The stable TNA-based GO sensing nanoplatform holds promise for disease diagnosis, enabling rapid and accurate detection and imaging of various disease-related nucleic acid molecules at the in vivo level. STATEMENT OF SIGNIFICANCE: The study's significance lies in the development of the GO-TNA biosensor, which addresses limitations in nucleic acid detection. By utilizing chemically modified nucleic acid analogues, the biosensor offers improved reliability and specificity, distinguishing single nucleobase mismatches and avoiding false signals. Additionally, its ability to detect and image target nucleic acids in vivo facilitates studying disease mechanisms. The simplified preparation process enhances practicality and accessibility, enabling real-time analysis. The biosensor's potential applications extend beyond healthcare, contributing to environmental analysis and food safety. Overall, this study's findings have substantial implications for disease diagnosis, biomedical research, and diverse applications, advancing nucleic acid detection and its impact on various fields.

Nanoplatform-Mediated Autophagy Regulation and Combined Anti-Tumor Therapy for Resistant Tumors.

The overall cancer incidence and death toll have been increasing worldwide. However, the conventional therapies have some obvious limitations, such as non-specific targeting, systemic toxic effects, especially the multidrug resistance (MDR) of tumors, in which, autophagy plays a vital role. Therefore, there is an urgent need for new treatments to reduce adverse reactions, improve the treatment efficacy and expand their therapeutic indications more effectively and accurately. Combination therapy based on autophagy regulators is a very feasible and important method to overcome tumor resistance and sensitize anti-tumor drugs. However, the less improved efficacy, more systemic toxicity and other problems limit its clinical application. Nanotechnology provides a good way to overcome this limitation. Co-delivery of autophagy regulators combined with anti-tumor drugs through nanoplatforms provides a good therapeutic strategy for the treatment of tumors, especially drug-resistant tumors. Notably, the nanomaterials with autophagy regulatory properties have broad therapeutic prospects as carrier platforms, especially in adjuvant therapy. However, further research is still necessary to overcome the difficulties such as the safety, biocompatibility, and side effects of nanomedicine. In addition, clinical research is also indispensable to confirm its application in tumor treatment.

Neutrophil-like pH-responsive pro-efferocytic nanoparticles improve neurological recovery by promoting erythrophagocytosis after intracerebral hemorrhage.

Rationale: Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disease resulting from blood extravasating into the brain parenchyma. Escalation of erythrophagocytosis (a form of efferocytosis), avoiding the consequent release of the detrimental erythrocyte lysates, may be a promising target of ICH management. The ADAM17 inhibitor and liver X receptor (LXR) agonist could promote efficient efferocytosis and injury repair. Nevertheless, the poor bioavailability and restriction of the blood-brain barrier (BBB) hinder their application. Therefore, it is needed that biocompatible and smart nanoplatforms were designed and synthesized to realize effective therapy targeting erythrophagocytosis. Methods: We first assessed the synergistic effect of therapeutic GW280264X (an ADAM17 inhibitor) and desmosterol (an LXR agonist) on erythrophagocytosis in vitro. Then a pH-responsive neutrophil membrane-based nanoplatform (NPEOz) served as a carrier to accurately deliver therapeutic GW280264X and desmosterol to the damaged brain was prepared via co-extrusion. Afterwards, their pH-responsive performance was valued in vitro and targeting ability was assessed through fluorescence image in vivo. Finally, the pro-erythrophagocytic and anti-neuroinflammatory ability of the nanomedicine and related mechanisms were investigated. Results: After the synergistical effect of the above two drugs on erythrophagocytosis was confirmed, we successfully developed neutrophil-disguised pH-responsive nanoparticles to efficiently co-deliver them. The nanoparticles could responsively release therapeutic agents under acidic environments, and elicit favorable biocompatibility and ability of targeting injury sites. D&G@NPEOz nanoparticles enhanced erythrophagocytosis through inhibiting shedding of the efferocytotic receptors MERTK/AXL mediated by ADAM17 and accelerating ABCA-1/ABCG-1-mediated cholesterol efflux regulated by LXR respectively. In addition, the nano-formulation was able to modulate the inflammatory microenvironment by transforming efferocytes towards a therapeutic phenotype with reducing the release of proinflammatory cytokines while increasing the secretion of anti-inflammatory factors, and improve neurological function. Conclusions: This biomimetic nanomedicine is envisaged to offer an encouraging strategy to effectively promote hematoma and inflammation resolution, consequently alleviate ICH progression.

Sequential-Crosslinking Fibrin Glue for Rapid and Reinforced Hemostasis.

Achieving hemostasis effectively is essential for surgical success and excellent patient outcomes. However, it is challenging to develop hemostatic adhesives that are fast-acting, strongly adherent, long-lasting, and biocompatible for treating hemorrhage. In this study, a sequential crosslinking fibrin glue (SCFG) is developed, of which the first network of the fibrin glue forms in situ within 2 s to act as an initial physical barrier and locks the gelatin methacryloyl precursor for tight construction of the second network to enhance wet adhesion and durability for tissues covered with blood. The sequential crosslinking glue can provide large pressures (≈280 mmHg of burst pressure), makes strong (38 kPa of shear strength) and tough (≈60 J m-2 of interfacial toughness) interfaces with wet tissues, and outperforms commercial hemostatic agents and gelatin methacryloyl. SCFG are demonstrated as an effective and safe sealant to enhance the treatment outcomes of bleeding tissues in rat, rabbit, and pig models. The ultrafast gelation, strong adhesion and durability, excellent compatibility, and easy manufacture of SCFG make it a promising hemostatic adhesive for clinical applications.

Living virus-based nanohybrids for biomedical applications.

Living viruses characterized by distinctive biological functions including specific targeting, gene invasion, immune modulation, and so forth have been receiving intensive attention from researchers worldwide owing to their promising potential for producing numerous theranostic modalities against diverse pathological conditions. Nevertheless, concerns during applications, such as rapid immune clearance, altering immune activation modes, insufficient gene transduction efficiency, and so forth, highlight the crucial issues of excessive therapeutic doses and the associated biosafety risks. To address these concerns, synthetic nanomaterials featuring unique physical/chemical properties are frequently exploited as efficient drug delivery vehicles or treatments in biomedical domains. By constant endeavor, researchers nowadays can create adaptable living virus-based nanohybrids (LVN) that not only overcome the limitations of virotherapy, but also combine the benefits of natural substances and nanotechnology to produce novel and promising therapeutic and diagnostic agents. In this review, we discuss the fundamental physiochemical properties of the viruses, and briefly outline the basic construction methodologies of LVN. We then emphasize their distinct diagnostic and therapeutic performances for various diseases. Furthermore, we survey the foreseeable challenges and future perspectives in this interdisciplinary area to offer insights. This article is categorized under: Biology-Inspired Nanomaterials > Protein and Virus-Based Structures Therapeutic Approaches and Drug Discovery > Emerging Technologies.