Bacteria-based biohybrids for remodeling adenosine-mediated immunosuppression to boost radiotherapy-triggered antitumor immune response.

Radiotherapy (RT) can trigger immunogenic cell death (ICD) in tumor cells and release adenosine triphosphate (ATP) to activate antitumor immunity. However, the formation of immunosuppressive adenosine (ADO) mediated by ectonucleotidases including CD39 and CD73, can exacerbate the immunosuppressive effects. Herein, a radiosensitizer-based metal-organic framework (MOF) composed of bismuth (Bi) and ellagic acid (EA) was synthesized in situ on the surface of Escherichia coli Nissle 1917 (EcN) to serve as a carrier for the CD39 inhibitor sodium polyoxotungstate (POM-1).

Petaloid Metal-Organic Frameworks for Resiquimod Delivery To Potentiate Antitumor Immunity.

The morphological features of materials significantly influence their interactions with cells, consequently affecting the cellular uptake of these materials. In this study, we examine the cellular uptake behavior of spherical metal-organic frameworks (MOFs) and petaloid MOFs, both possessing similar sizes and compositions. In comparison to spherical MOFs, dendritic cells (DCs) and macrophages exhibit superior phagocytic uptake of petaloid MOFs.

Design strategies for enhancing antitumor efficacy through tumor microenvironment exploitation using albumin-based nanosystems: A review.

The tumor microenvironment (TME) is a complex and dynamic system that plays a crucial role in regulating cancer progression, treatment response, and the emergence of acquired resistance mechanisms. The TME is usually featured by severe hypoxia, low pH values, high hydrogen peroxide (HO) concentrations, and overproduction of glutathione (GSH). The current development of intelligent nanosystems that respond to TME has shown great potential to enhance the efficacy of cancer treatment.

Reactive Oxygen Species-Triggered Curcumin Release from Hollow Mesoporous Silica Nanoparticles for PM-Induced Acute Lung Injury Treatment.

Exposure to fine particulate matter with a diameter ≤2.5 μm (PM) can result in serious inflammation and oxidative stress in lung tissue. However, there is presently very few effective treatments for PM-induced many pulmonary diseases, such as acute lung injury (ALI).

Microbial synthesis of Prussian blue for potentiating checkpoint blockade immunotherapy.

Cancer immunotherapy is revolutionizing oncology. The marriage of nanotechnology and immunotherapy offers a great opportunity to amplify antitumor immune response in a safe and effective manner. Here, electrochemically active Shewanella oneidensis MR-1 can be applied to produce FDA-approved Prussian blue nanoparticles on a large-scale.

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.

Biomineralized MnO Nanoplatforms Mediated Delivery of Immune Checkpoint Inhibitors with STING Pathway Activation to Potentiate Cancer Radio-Immunotherapy.

Radiotherapy (RT), as one of the main methods in the clinical treatment of various malignant tumors, would induce systemic immunotherapeutic effects by triggering immunogenic cell death (ICD) of cancer cells. However, the antitumor immune responses produced by RT-induced ICD alone usually are not robust enough to eliminate distant tumors and thus ineffective against cancer metastases. Herein, a biomimetic mineralization method for facile synthesis of MnO nanoparticles with high anti-programmed death ligand 1 (αPDL1) encapsulation efficiency (αPDL1@MnO) is proposed to reinforce RT-induced systemic antitumor immune responses.

Directing the Architecture of Surface-Clean CuO for CO Electroreduction.

Tailoring the morphology of nanocrystals is a promising way to enhance their catalytic performance. In most previous shape-controlled synthesis strategies, surfactants are inevitable due to their capability to stabilize different facets. However, the adsorbed surfactants block the intrinsic active sites of the nanocrystals, reducing their catalytic performance.

Albumin-Based Therapeutics Capable of Glutathione Consumption and Hydrogen Peroxide Generation for Synergetic Chemodynamic and Chemotherapy of Cancer.

A nanoscale therapeutic system with good biocompatibility was facilely fabricated by the coassembly of human serum albumin and glucose oxidase (GOD), where the former was pretreated with metal ions through a chelating agent or the chemotherapeutic prodrug oxaliplatin (Oxa(IV)). Among different chelating metal ions used, Mn ion was selected to produce hydroxyl radical (•OH) efficiently through Fenton-like reaction, while GOD loaded in the system was able to generate a large amount of hydrogen peroxide for promoting efficient conversion into highly toxic •OH. In the meanwhile, the conversion of the Oxa(IV) prodrug into chemotherapeutic Oxa(II) was beneficial for the consumption of glutathione, thereby enhancing the chemodynamic therapy (CDT) efficacy.

Multifunctional MnO nanoparticles for tumor microenvironment modulation and cancer therapy.

Tumor microenvironment (TME) is generally featured by low pH values, high glutathione (GSH) concentrations, overproduced hydrogen peroxide (H O ), and severe hypoxia. These characteristics could provide an interior environment for origination and residence of tumor cells and would lead to tumor progression, metastasis, and drug resistance. Therefore, the development of TME-responsive smart nanosystems has shown significant potential to enhance the efficacy of current cancer treatments.

pH-Sensitive Biomaterials for Drug Delivery.

The development of precise and personalized medicine requires novel formulation strategies to deliver the therapeutic payloads to the pathological tissues, producing enhanced therapeutic outcome and reduced side effects. As many diseased tissues are feathered with acidic characteristics microenvironment, pH-sensitive biomaterials for drug delivery present great promise for the purpose, which could protect the therapeutic payloads from metabolism and degradation during in vivo circulation and exhibit responsive release of the therapeutics triggered by the acidic pathological tissues, especially for cancer treatment. In the past decades, many methodologies, such as acidic cleavage linkage, have been applied for fabrication of pH-responsive materials for both in vitro and in vivo applications.

Metal-Organic Framework Derived Multicomponent Nanoagent as a Reactive Oxygen Species Amplifier for Enhanced Photodynamic Therapy.

Intracellular antioxidants such as glutathione (GSH) play a critical role in protecting malignant tumor cells from apoptosis induced by reactive oxygen species (ROS) and in mechanisms of multidrug and radiation resistance. Herein, we rationally design two multicomponent self-assembled photodynamic therapy (PDT) nanoagents, that is, Glup-MFi-c and Glud-MFo-c, which consist of respective GSH-passivation and GSH-depletion linkers in metal-organic frameworks encapsulated with photosensitizers for a deeply comprehensive understanding of GSH-based tumor PDT. Multicomponent coordination, π-π stacking, and electrostatic interactions among metal ions, photosensitizers, and bridging linkers under the protection of a biocompatible polymer generate homogeneous nanoparticles with satisfied size, good colloid stability, and ultrahigh loading capacity.

Self-assembled single-atom nanozyme for enhanced photodynamic therapy treatment of tumor.

Hypoxia of solid tumor compromises the therapeutic outcome of photodynamic therapy (PDT) that relies on localized O molecules to produce highly cytotoxic singlet oxygen (O) species. Herein, we present a safe and versatile self-assembled PDT nanoagent, i.e.

Structural Engineering of Luminogens with High Emission Efficiency Both in Solution and in the Solid State.

Developing molecules with high emission efficiency both in solution and the solid state is still a great challenge, since most organic luminogens are either aggregation-caused quenching or aggregation-induced emission molecules. This dilemma was overcome by integrating planar and distorted structures with long alkyl side chains to achieve DAπAD type emitters. A linear diphenyl-diacetylene core and the charge transfer effect ensure considerable planarity of these molecules in the excited state, allowing strong emission in dilute solution (quantum yield up to 98.

A Hypoxia-Responsive Albumin-Based Nanosystem for Deep Tumor Penetration and Excellent Therapeutic Efficacy.

Uncontrolled cancer cell proliferation, insufficient blood flow, and inadequate endogenous oxygen lead to hypoxia in tumor tissues. Herein, a unique type of hypoxia-responsive human serum albumin (HSA)-based nanosystem (HCHOA) is reported, prepared by cross-linking the hypoxia-sensitive azobenzene group between photosensitizer chlorin e6 (Ce6)-conjugated HSA (HC) and oxaliplatin prodrug-conjugated HSA (HO). The HCHOA nanosystem is stable under normal oxygen partial pressure with a size of 100-150 nm.

Self-Assembled Oxaliplatin(IV) Prodrug-Porphyrin Conjugate for Combinational Photodynamic Therapy and Chemotherapy.

Nanomedicine has emerged as a promising strategy for effective cancer treatment. A useful approach is to develop carrier-free nanodrugs via a facile supramolecular self-assembly process. To achieve high therapeutic effect, integrating photodynamic therapy with chemotherapy has been sought after.

Catalase-Integrated Hyaluronic Acid as Nanocarriers for Enhanced Photodynamic Therapy in Solid Tumor.

Photodynamic therapy (PDT) as a treatment method has many advantages such as minimal invasiveness, repeatable dosage, and low systemic toxicity. Issues with conventional PDT agents include the limited availability of endogenous oxygen and difficulty in accumulation at the tumor site, which has hindered the successful treatment of tumors. Herein, we developed catalase-encapsulated hyaluronic-acid-based nanoparticles loaded with adamantane-modified photosensitizer for enhanced PDT of solid tumors.

Degradability and Clearance of Inorganic Nanoparticles for Biomedical Applications.

Inorganic nanoparticles with tunable and diverse properties hold tremendous potential in the field of nanomedicine, while having non-negligible toxicity concerns in healthy tissues/organs that have resulted in their restricted clinical translation to date. In the past decade, the emergence of biodegradable or clearable inorganic nanoparticles has made it possible to completely solve this long-standing conundrum. A comprehensive understanding of the design of these inorganic nanoparticles with their metabolic performance in the body is of crucial importance to advance clinical trials and expand their biological applications in disease diagnosis.

Control on Dimensions and Supramolecular Chirality of Self-Assemblies through Light and Metal Ions.

Precise control over helical chirality and dimensions of molecular self-assemblies, a remaining challenge for both chemists and materials scientists, is the key to manipulate the property and performance of supramolecular materials. Herein, we report that a cholesterol-azopyridine conjugate could self-assemble into organogels with photocontrollable dimensional transition from 2D microbelts to 1D nanotubes and finally to 0D nanoparticles. The E/ Z-Photoisomerization of the 4-azopyridine unit is the major driving force for the dimensional transformation.

Controlling Supramolecular Chirality of Two-Component Hydrogels by J- and H-Aggregation of Building Blocks.

While manipulating the helicity of nanostructures is a challenging task, it attracts great research interest on account of its crucial role in better understanding the formation mechanisms of helical systems. For the supramolecular chirality in self-assembly systems, one challenge is how to understand the origin of supramolecular chirality and inherent helicity information on nanostructures regulated by functionality-oriented stacking modes (such as J- and H-aggregation) of building blocks. Herein, two-component hydrogels were prepared by phenylalanine-based enantiomers and achiral bis(pyridinyl) derivatives, where helical nanofibers with inverse handedness as well as controllable helical pitch and diameter were readily obtained through stoichiometric coassembly of these building blocks.

Smart Nanoreactors for pH-Responsive Tumor Homing, Mitochondria-Targeting, and Enhanced Photodynamic-Immunotherapy of Cancer.

Photodynamic therapy (PDT) is an oxygen-dependent light-triggered noninvasive therapeutic method showing many promising aspects in cancer treatment. For effective PDT, nanoscale carriers are often needed to realize tumor-targeted delivery of photosensitizers, which ideally should further target specific cell organelles that are most vulnerable to reactive oxygen species (ROS). Second, as oxygen is critical for PDT-induced cancer destruction, overcoming hypoxia existing in the majority of solid tumors is important for optimizing PDT efficacy.

Manganese Dioxide Coated WS @Fe O /sSiO Nanocomposites for pH-Responsive MR Imaging and Oxygen-Elevated Synergetic Therapy.

Recently, the development of multifunctional theranostic nanoplatforms to realize tumor-specific imaging and enhanced cancer therapy via responding or modulating the tumor microenvironment (TME) has attracted tremendous interests in the field of nanomedicine. Herein, tungsten disulfide (WS ) nanoflakes with their surface adsorbed with iron oxide nanoparticles (IONPs) via self-assembly are coated with silica and then subsequently with manganese dioxide (MnO ), on to which polyethylene glycol (PEG) is attached. The obtained WS -IO/S@MO-PEG appears to be highly sensitive to pH, enabling tumor pH-responsive magnetic resonance imaging with IONPs as the pH-inert T2 contrast probe and MnO as the pH-sensitive T1 contrast probe.

Hollow MnO as a tumor-microenvironment-responsive biodegradable nano-platform for combination therapy favoring antitumor immune responses.

Herein, an intelligent biodegradable hollow manganese dioxide (H-MnO) nano-platform is developed for not only tumor microenvironment (TME)-specific imaging and on-demand drug release, but also modulation of hypoxic TME to enhance cancer therapy, resulting in comprehensive effects favoring anti-tumor immune responses. With hollow structures, H-MnO nanoshells post modification with polyethylene glycol (PEG) could be co-loaded with a photodynamic agent chlorine e6 (Ce6), and a chemotherapy drug doxorubicin (DOX). The obtained H-MnO-PEG/C&D would be dissociated under reduced pH within TME to release loaded therapeutic molecules, and in the meantime induce decomposition of tumor endogenous HO to relieve tumor hypoxia.

Light-controlled drug release from singlet-oxygen sensitive nanoscale coordination polymers enabling cancer combination therapy.

The development of smart drug delivery systems to realize controlled drug release for highly specific cancer treatment has attracted tremendous attention. Herein, nanoscale coordination polymers (NCPs) constructed from hafnium ions and bis-(alkylthio) alkene (BATA), a singlet-oxygen responsive linker, are fabricated and applied as nanocarriers to realize light-controlled drug release under a rather low optical power density. In this system, NCPs synthesized through a solvothermal method are sequentially loaded with chlorin e6 (Ce6), a photosensitizer, and doxorubicin (DOX), a chemotherapeutic drug, and then coated with lipid bilayer to allow modification with polyethylene glycol (PEG) to acquire excellent colloidal stability.