Light-triggered toll-like receptor activation in a nanoscale metal-organic framework for synergistic PDT and cancer immunotherapy.

Although innate immune modulators (IIMs) have shown promise as cancer immunotherapeutics, their clinical application is hindered by the challenge of achieving tumour-specific activation while minimizing systemic immune-related toxicity. Nanoscale metal-organic frameworks (MOFs) have emerged as effective carriers for photosensitizers to enable photodynamic therapy (PDT), which induces immunogenic cell death reactive oxygen species (ROS) generation. We hypothesized that covalent conjugation of IMMs to nanoscale MOFs through ROS-cleavable linkers could localize immune activation to the tumour microenvironment while synergizing with PDT to enhance antitumour immunity.

Functionalized Bottlebrush Polymers as Bioinspired Photocatalysts for Highly Efficient Organic Transformations.

Bioinspired catalysts replicate key catalytic functions of natural enzymes and offer innovative solutions to challenges in chemical synthesis, energy conversion, and environmental sustainability. In this study, bottlebrush polymers are synthesized via ring-opening metathesis polymerization (ROMP) and their use as bioinspired photocatalysts. By precisely controlling the degrees of polymerization, monomer composition and sequence, and the architecture of macromonomers, phenoxazine photosensitizer and/or bipyridine-nickel complexes are incorporated into bottlebrush polymers to afford photoredox and dual photocatalysts.

Nanoscale Donor-Acceptor Covalent Organic Frameworks for Mitochondria-Targeted Sonodynamic Therapy and Antitumor Immunity.

Sonodynamic therapy (SDT) based on O-dependent type II sonosensitizers (SSs) is limited by the hypoxic tumor microenvironment and aggregation-induced quenching (AIQ) of SSs. Type I SSs can generate reactive oxygen species (ROS) with reduced O dependence, but their efficacy is still constrained by the high electron-hole recombination rates and low ROS yields. Here, we report the synthesis of a novel two-dimensional nanoscale covalent organic framework (nCOF), Td-Pc, for mitochondria-targeted type I/II SDT.

Isostructural chiral metal-organic frameworks for enantioselective luminescence sensing of 1-phenyl-1,2-ethanediol.

We report the synthesis of isostructural chiral metal-organic frameworks (CMOFs), Zn-L-(Et), Zn-L-Me and Zn-L, based on Zn paddle-wheel secondary building units and three 1,1'-bi-2-naphthol (BINOL)-derived tetrabenzoate ligands [L-(Et), L-Me, and L], featuring different alkyl substituents at the 2,2'-hydroxyl positions. These CMOFs were evaluated as luminescent sensors for the enantiomers of 1-phenyl-1,2-ethanediol (PE). All three CMOF sensors exhibited selective quenching of -PE over -PE, with significantly higher quenching efficiencies than their corresponding free ligands.

Steering artificial photosynthesis via photoinduced conversion of monometallic to bimetallic sites in FeCo nitroprussides.

Artificial photosynthesis provides an efficient strategy for solar energy storage via water splitting and CO reduction, but it remains a challenge in tuning artificial photosynthesis between these two competing reactions. Herein, we demonstrate photoinduced conversion of monometallic to bimetallic sites in a Fe-Co nitroprusside (FeCo-NP) to steer the reaction path from H evolution to CO reduction. Monometallic Co sites achieve efficient H production with 28.

Gram-Scale Green-Synthesis of High Purity Pinacols and Amides by Continuous Tandem Photocatalysis via a Negative Carbon Emission Process.

Solar-driven CO reduction for practical applications confronts significant challenges, including the waste of oxidation power and the difficulty in isolating reduction products. Herein, a pre-coordination restriction strategy is presented to hierarchically assemble CdS quantum dots (QDs), cobalt sites and Zr clusters in one metal-organic framework (MOF), resulting in the CdS@PCN-Co composite for simultaneous CO photoreduction and C-C coupling. Impressively, the yields of CO and pinacols with CdS@PCN-Co can reach 59.

Machine Learning Reveals In-Cavity Versus Surface Activity for Selective C─H Borylation by Metal-Organic Framework Catalysts.

Metal-organic frameworks (MOFs) provide an expansive and tunable platform for heterogeneous catalysis, yet distinguishing between catalytic reactions occurring within their pores and those on their external surfaces remains a challenge. This study employs interpretable machine learning to elucidate structure-activity relationships in MOF-supported nickel (Ni) catalysts for selective sp and sp C─H borylation. By analyzing over 470 000 MOF structures, we developed a set of 45 concise and chemically meaningful descriptors that capture key structural variations across MOFs.

Transforming malignant tumors into vulnerable phenotypes via nanoscale coordination polymer mediated cell senescence and photodynamic therapy.

Induction of senescence in cancer cells can thwart the proliferation of malignant tumors. Herein we report the design of AZT-P/pyro nanoscale coordination polymer particles consisting of 3-azido-2,3-dideoxythymidine monophosphate (AZT-P) in the core and photosensitizing pyro-lipid (pyro) in the shell for potent antitumor treatment. Gradual release of AZT-P in response to an acidic tumor microenvironment transforms cancer cells with unlimited proliferation capacity into senescent cells that are vulnerable to reactive oxygen species (ROS).

Viologen Covalent Organic Framework Mediates Near-Infrared Light-Induced Electron Transfer for Catalytic Oxidative Coupling Reactions.

Near-infrared (NIR) light-driven photoreactions are advantageous over visible light-driven ones because NIR photons have lower energy and fewer side reactions, deeper penetration in reaction media, and high abundance in the solar spectrum. However, currently available covalent organic frameworks (COFs) absorb in the UV-vis region and catalyze photoreactions under blue or white light irradiation. Herein, we report a linker-to-linker charge transfer process in a viologen-linked porphyrin COF (Vio-COF), leading to a novel type of hyperporphyrin effect and extending the absorption into the NIR region with an absorption edge at 998 nm.

Serum-biomarker-based population screening model for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) early identification is crucial for improving patient outcomes. Current screening methods are often complex and costly. This study developed a simplified, cost-effective HCC screening model using serum marker data.

Nanoparticle-Mediated Toll-Like Receptor Activation and Dual Immune Checkpoint Downregulation for Potent Cancer Immunotherapy.

Dual blockade of CD47 and PD-L1 immune checkpoints has shown potential in cancer treatment, but its clinical application is hindered by the on-target off-tumor immunotoxicities of monoclonal antibodies. Herein, we report a core-shell nanoparticle, PPA/HG, comprising polyinosinic: polycytidylic acid (PPA) in the core and a cholesterol-conjugated prodrug of 3-(hydroxyolinoyl)glycine (HG) on the shell, for potent cancer immunotherapy. PPA/HG shows a long half-life in the bloodstream to efficiently accumulate in tumors, where PPA/HG rapidly releases HG and PPA.

Metal-organic layer delivers 3-bromopyruvate to mitochondria for metabolic regulation and cancer radio-immunotherapy.

Abnormal cancer metabolism causes hypoxia and immunosuppression, limiting the anti-tumor efficacy of radiotherapy. Herein, we report a positively charged, mitochondria-targeted nanoscale metal-organic layer conjugated with 3-bromopyruvate (BP), BP/Hf-Ir, for metabolic reprogramming and radiosensitization. BP/Hf-Ir disrupts oxidative phosphorylation and glycolysis, reducing energy production and alleviating hypoxia to enhance radiotherapy and anti-tumor immunity.

Homochiral BINOL-Based Metal-Organic Frameworks for Luminescence Sensing of Hydrobenzoin Enantiomers.

Luminescent chiral metal-organic frameworks (CMOFs) are promising candidates for the enantioselective sensing of important chiral molecules. Herein, we report the synthesis and characterization of Zn and Cd CMOFs based on 1,1'-bi-2-naphthol (BINOL)-derived 3,3',6,6'-tetra(benzoic acids), H-OEt and H-OH. Four CMOFs, -OEt, -OH, -OEt, and -OH, based on these ligands were crystallographically characterized.

Innate Immune Activation with Multifunctional Nanoparticles for Cancer Immunotherapy.

Immune checkpoint blockade (ICB) has revolutionized the treatment of many cancers by leveraging the immune system to combat malignancies. However, its efficacy is limited by the immunosuppressive tumor microenvironment and other regulatory mechanisms of the immune system. Innate immune modulators (IIMs) provide potent immune activation to complement adaptive immune responses and help overcome resistance to ICB.

Nitric Oxide-Releasing Nanoscale Metal-Organic Layer Overcomes Hypoxia and Reactive Oxygen Species Diffusion Barriers to Enhance Cancer Radiotherapy.

Hafnium (Hf)-based nanoscale metal-organic layers (MOLs) enhance radiotherapeutic effects of tissue-penetrating X-rays via a unique radiotherapy-radiodynamic therapy (RT-RDT) process through efficient generation of hydroxy radical (RT) and singlet oxygen (RDT). However, their radiotherapeutic efficacy is limited by hypoxia in deep-seated tumors and short half-lives of reactive oxygen species (ROS). Herein the conjugation of a nitric oxide (NO) donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), to the Hf secondary building units (SBUs) of Hf-5,5'-di-p-benzoatoporphyrin MOL is reported to afford SNAP/MOL for enhanced cancer radiotherapy.

Erratum: Ultrathin Metal-Organic-Layer Mediated Radiotherapy-Radiodynamic Therapy.

[This corrects the article PMC7442115.].

Nanoscale Mixed-Ligand Metal-Organic Framework for X-ray Stimulated Cancer Therapy.

Concurrent localized radiotherapy and systemic chemotherapy are standards of care for many cancers, but these treatment regimens cause severe adverse effects in many patients. Herein, we report the design of a mixed-ligand nanoscale metal-organic framework (nMOF) with the ability to simultaneously enhance radiotherapeutic effects and trigger the release of a potent chemotherapeutic under X-ray irradiation. We synthesized a new functional quaterphenyl dicarboxylate ligand conjugated with SN38 (HQP-SN) via a hydroxyl radical-responsive covalent linkage.

Cationic Metal-Organic Layer Delivers siRNAs to Overcome Radioresistance and Potentiate Cancer Radiotherapy.

Radiotherapy plays an important role in modern oncology, but its treatment efficacy is limited by the radioresistance of tumor cells. As a member of the inhibitor of apoptosis protein family, survivin plays a key role in developing radioresistance by mediating apoptosis evasion, promoting epithelial-mesenchymal transition, and modulating cell cycle dynamics. Efficient downregulation of survivin expression presents a promising strategy to enhance the antitumor effects of radiotherapy.

Morphology-Mediated Tumor Deep Penetration for Enhanced Near Infrared II Photothermal and Chemotherapy of Colorectal Cancer.

The low permeability and heterogeneous distribution of drugs (including nanomedicines) have limited their deep penetration into solid tumors. Herein we report the design of gold nanoparticles with virus-like spikes (AuNVs) to mimic viral shapes and facilitate tumor penetration. Mechanistic studies revealed that AuNVs mainly entered cells through macropinocytosis, then transported to the Golgi/endoplasmic reticulum system via Rab11-regulated pathway, and finally exocytosed through recycling endosomes, leading to high cellular uptake, effective transcytosis, and deep tumor penetration compared to gold nanospheres (AuNPs) and gold nanostars (AuNSs).

Optically accessible long-lived electronic biexcitons at room temperature in strongly coupled H- aggregates.

Photon absorption is the first process in light harvesting. Upon absorption, the photon redistributes electrons in the materials to create a Coulombically bound electron-hole pair called an exciton. The exciton subsequently separates into free charges to conclude light harvesting.

Digitonin-Loaded Nanoscale Metal-Organic Framework for Mitochondria-Targeted Radiotherapy-Radiodynamic Therapy and Disulfidptosis.

The efficacy of radiotherapy (RT) is limited by inefficient X-ray absorption and reactive oxygen species generation, upregulation of immunosuppressive factors, and a reducing tumor microenvironment (TME). Here, the design of a mitochondria-targeted and digitonin (Dig)-loaded nanoscale metal-organic framework, Th-Ir-DBB/Dig, is reported to overcome these limitations and elicit strong antitumor effects upon low-dose X-ray irradiation. Built from ThO(OH) secondary building units (SBUs) and photosensitizing Ir(DBB)(ppy) (Ir-DBB, DBB = 4,4'-di(4-benzoato)-2,2'-bipyridine; ppy = 2-phenylpyridine) ligands, Th-Ir-DBB exhibits strong RT-radiodynamic therapy (RDT) effects via potent radiosensitization with high-Z SBUs for hydroxyl radical generation and efficient excitation of Ir-DBB ligands for singlet oxygen production.