Genetically Engineered Bacteria as A Living Bioreactor for Monitoring and Elevating Hypoxia-Activated Prodrug Tumor Therapy.

Tirapazamine (TPZ), an antitumor prodrug, can be activated in hypoxic environment. It specifically targets the hypoxic microenvironment of tumors and produces toxic free radicals. However, due to the tumor is not completely hypoxic, TPZ often fails to effectively treat the entire tumor tissue, resulting in suboptimal therapeutic outcomes.

A Minimalist Pathogen-Like Sugar Nanovaccine for Enhanced Cancer Immunotherapy.

Pathogen-mimicking nanoparticles have emerged at the forefront of vaccine delivery technology, offering potent immune activation and excellent biocompatibility. Among these innovative carriers, mannan, a critical component of yeast cell walls, shows promise as an exemplary vaccine carrier. Nevertheless, it faces challenges like unpredictable immunogenicity, rapid elimination, and limited antigen loading due to high water solubility.

An emerging antibacterial nanovaccine for enhanced chemotherapy by selectively eliminating tumor-colonizing bacteria.

Fusobacterium nucleatum (F. nucleatum), an oral anaerobe, is prevalent in colorectal cancer and is closely related to increased cancer cell growth, metastasis, and poor treatment outcomes. Bacterial vaccines capable of selectively eliminating bacteria present a promising approach to targeting intratumor F.

Turning Waste into Wealth: A Potent Sono-Immune Strategy Based on Microcystis.

Currently, sonodynamic therapy (SDT) has limited therapeutic outcomes and immune responses, highlighting the urgent need for enhanced strategies that can stimulate robust and long-lasting antitumor effects. Microcystis, a notorious microalga, reveals the possibility of mediating SDT owing to the presence of gas vesicles (GVs) and phycocyanin (PC). Herein, a nontoxic strain of Microcystis elabens (labeled Me) is developed as a novel agent for SDT because it generates O under red light (RL) illumination, while GVs and PC act as cavitation nuclei and sonosensitizers, respectively.

Engineered probiotics with sustained release of interleukin-2 for the treatment of inflammatory bowel disease after oral delivery.

Inflammatory bowel disease (IBD) is a kind of auto-immune disease characterized by disrupted intestinal barrier and mucosal epithelium, imbalanced gut microbiome and deregulated immune responses. Therefore, the restoration of immune equilibrium and gut microbiota could potentially serve as a hopeful approach for treating IBD. Herein, the oral probiotic Escherichia coli Nissle 1917 (ECN) was genetically engineered to express secretable interleukin-2 (IL-2), a kind of immunomodulatory agent, for the treatment of IBD.

Bioactive Layered Double Hydroxides for Synergistic Sonodynamic/Cuproptosis Anticancer Therapy with Elicitation of the Immune Response.

Sonodynamic therapy (SDT) has promising application prospects in tumor therapy. However, SDT does not eradicate metastatic tumors. Herein, Cu-substituted ZnAl ternary layered double hydroxide nanosheets (ZCA NSs) were developed as both sonosensitizers and copper nanocarriers for synergistic SDT/cuproptosis cancer therapy.

Emerging Co-Assembled and Sustained Released Natural Medicinal Nanoparticles for Multitarget Therapy of Choroidal Neovascularization.

Age-related macular degeneration (AMD) disease has become a worldwide senile disease, and frequent intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is the mainstream treatment in the clinic, which is associated with sight-threatening complications. Herein, nintedanib, an inhibitor of angiogenesis, and lutein, a potent antioxidant, can co-assemble into nanoparticles through multiple noncovalent interactions. Interestingly, the co-assembled lutein/nintedanib nanoparticles (L/N NPs) exhibit significantly improved stability and achieve long-term sustained release of two drugs for at least two months in mice.

Minimalist Nanovaccine with Optimized Amphiphilic Copolymers for Cancer Immunotherapy.

Cancer vaccines with the ability to elicit tumor-specific immune responses have attracted significant interest in cancer immunotherapy. A key challenge for effective cancer vaccines is the spatiotemporal codelivery of antigens and adjuvants. Herein, we synthesized a copolymer library containing nine poly(ethylene glycol) methyl ether methacrylate--butyl methacrylate--2-(azepan-1-yl)ethyl methacrylate (PEGMA--BMA--C7AMA) graft copolymers with designed proportions of different components to regulate their properties.

Delivery of short chain fatty acid butyrate to overcome Fusobacterium nucleatum-induced chemoresistance.

The gut microbiota is closely associated with the progression of colorectal cancer (CRC) in which Fusobacterium nucleatum (F. nucleatum) was found to induce cancer resistance to chemotherapeutics. To relieve F.

Antibacterial Fusobacterium nucleatum-Mimicking Nanomedicine to Selectively Eliminate Tumor-Colonized Bacteria and Enhance Immunotherapy Against Colorectal Cancer.

Clinical evidence indicates that tumor-colonizing bacteria can be closely related to the tumor development and therapeutic responses. Selectively eliminating bacteria within tumors may be an attractive approach to enhance cancer treatment without additional side effects. Herein, it is found that, owing to the high affinity between the membrane protein Fap-2 on Fusobacterium nucleatum and d-galactose-β (1-3)-N-acetyl-d-galactosamine (Gal-GalNAc) overexpressed on colorectal tumor cells, F.

X-ray-Induced Release of Nitric Oxide from Hafnium-Based Nanoradiosensitizers for Enhanced Radio-Immunotherapy.

Radiotherapy (RT) is an extensively used strategy for cancer treatment, but its therapeutic effect is usually limited by the abnormal tumor microenvironment (TME) and it lacks the ability to control tumor metastases. In this work, a nanoscale coordination polymer, Hf-nIm@PEG (HNP), is prepared by the coordination of hafnium ions (Hf ) with 2-nitroimidazole (2-nIm), and then modified with lipid bilayers containing poly(ethylene glycol) (PEG). Under low-dose X-ray irradiation, on the one hand, Hf with high computed tomography signal enhancement ability can deposit radiation energy to induce DNA damage, and on the other hand, NO can be persistently released from 2-nIm, which can not only directly react with the radical DNA to prevent the repair of damaged DNA but also relieves the hypoxic immunosuppressive TME to sensitize radiotherapy.

Regulating the Obesity-Related Tumor Microenvironment to Improve Cancer Immunotherapy.

Obesity usually induces systemic metabolic disturbances, including in the tumor microenvironment (TME). This is because adaptive metabolism related to obesity in the TME with a low level of prolyl hydroxylase-3 (PHD3) depletes the major fatty acid fuels of CD8 T cells and leads to the poor infiltration and unsatisfactory function of CD8 T cells. Herein, we discovered that obesity could aggravate the immunosuppressive TME and weaken CD8 T cell-mediated tumor cell killing.

Oral Delivery of Therapeutic Antibodies with a Transmucosal Polymeric Carrier.

Therapeutic proteins are playing increasingly important roles in treating numerous types of diseases. However, oral administration of proteins, especially large ones (e.g.

Eyedrop-based macromolecular ophthalmic drug delivery for ocular fundus disease treatment.

Therapeutic antibodies are extensively used to treat fundus diseases by intravitreal injection, as eyedrop formulation has been rather challenging due to the presence of ocular barriers. Here, an innovative penetrating carrier was developed for antibody delivery in eyedrop formulations. We found that fluorocarbon-modified chitosan (FCS) would self-assemble with proteins to form nanocomplexes, which could effectively pass across the complicated ocular structure to reach the posterior eye segments in both mice and rabbits.

Polymerization of Zwitterions on Therapeutic Proteins to Enable Their Effective Oral Delivery.

Oral administration of protein drugs has always been challenging owing to various intestinal barriers. Herein, we developed an efficient oral protein delivery strategy by using polymerization of zwitterions to encapsulate proteins, which were then loaded into enteric coated capsules for oral feeding. After oral administration of such capsules, the enteric coating would be degraded once the capsule enters the intestine, releasing polyzwitterion/protein nanocomplexes.

Microfluidic Production of Zwitterion Coating Microcapsules with Low Foreign Body Reactions for Improved Islet Transplantation.

Islet transplantation is a promising strategy for type 1 diabetes mellitus (T1DM) treatment, whereas implanted-associated foreign body reaction (FBR) usually induces the necrosis of transplanted islets and leads to the failure of glycemic control. Benefiting from the excellent anti-biofouling property of zwitterionic materials and their successful application in macroscopic implanted devices, microcapsules with zwitterionic coatings may be promising candidates for islet encapsulation. Herein, a series of zwitterion-coated core-shell microcapsules is fabricated (including carboxybetaine methacrylate [CBMA]-coated gelatin methacrylate [GelMA] [CBMA-GelMA], sulfobetaine methacrylate [SBMA]-coated GelMA [SBMA-GelMA], and phosphorylcholine methacrylate [MPC]-coated GelMA [MPC-GelMA]) by one-step photopolymerization of inner GelMA and outer zwitterionic monomers via a handmade two-fluid microfluidic device and it is demonstrated that they can effectively prevent protein adsorption, cell adhesion, and inflammation in vitro.

Immunosonodynamic Therapy Designed with Activatable Sonosensitizer and Immune Stimulant Imiquimod.

Sonodynamic therapy (SDT) has garnered extensive attention as a noninvasive treatment for deep tumors. Furthermore, imiquimod (R837), an FDA-approved toll-like receptor 7 agonist, is commonly used in clinical settings as an immune adjuvant. We prepared an activatable sonodynamic sensitizer platform (MR) based on glutathione-sensitive disulfide bonds linking Leu-MB, the reduced form of methylene blue (MB), and R837 to achieve efficient combinatory SDT and immunotherapy for tumors without harming normal tissues.

Programmable probiotics modulate inflammation and gut microbiota for inflammatory bowel disease treatment after effective oral delivery.

Reactive oxygen species (ROS) play vital roles in intestinal inflammation. Therefore, eliminating ROS in the inflammatory site by antioxidant enzymes such as catalase and superoxide dismutase may effectively curb inflammatory bowel disease (IBD). Here, Escherichia coli Nissle 1917 (ECN), a kind of oral probiotic, was genetically engineered to overexpress catalase and superoxide dismutase (ECN-pE) for the treatment of intestinal inflammation.

Orally administered titanium carbide nanosheets as anti-inflammatory therapy for colitis.

Oxidative stress, resulting from excessive reactive oxygen species (ROS), plays an important role in the initiation and progression of inflammatory bowel disease (IBD). Therefore, developing novel strategies to target the disease location and treat inflammation is urgently needed. Herein, we designed and developed a novel and effective antioxidant orally-administered nanoplatform based on simulated gastric fluid (SGF)-stabilized titanium carbide MXene nanosheets (TiC NSs) with excellent biosafety and multiple ROS-scavenging abilities for IBD therapy.

Inhalable nanocatchers for SARS-CoV-2 inhibition.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses.

A versatile chitosan nanogel capable of generating AgNPs in-situ and long-acting slow-release of Ag for highly efficient antibacterial.

Development of multifunctional antibacterial agent with long-lasting antibacterial activity and biofilm ablation performance is significant for the effective treatment of bacterial infections. Here, by utilizing the electrostatic interaction between sulfonated chitosan (SCS) and Ag and chitosan (CS), and the sodium borohydride reduction method, a versatile antibacterial agent (AgNPs@CS/SCS) capable of generating silver nanoparticles (AgNPs) in-situ and long-acting slow-release Ag was developed. AgNPs@CS/SCS has a good physiological stability and can long-acting slow-release of Ag due to the pH-dependent Ag release behavior of AgNPs.