Photothermal-gas combination therapy promotes checkpoint blockade immunotherapy in colon cancer.

Checkpoint blockade immunotherapy emerges as a potential cure of cancer, but the monotherapy suffers from a low response rate in clinic. Photothermal therapy (PTT) that harvests light energy to ablate tumor is reported to activate tumor-specific immune response, meanwhile nitric oxide (NO) is considered to involve in immune regulation. Herein, we designed a multifunctional nanoplatform that enables photothermal-gas combination therapy by conjugating indocyanine green-thiol (ICG-SH) and s-nitrosoglutathione (GSNO) onto polyvinyl pyrrolidone (PVP)-coated gold nanoparticles (AIG).

Effect of Amino Trimethylene Phosphonic Acid and Tartaric Acid on Compressive Strength and Water Resistance of Magnesium Oxysulfate Cement.

Organic acids could act as retarders in magnesium oxysulfide (MOS) systems, not only delaying setting and improving fluidity but also enhancing compressive strength and water resistance. These effects are generally attributed to both the presence of H ions and anion chelation. However, the enhancement efficiency of different organic acids in MOS systems varies significantly due to differences in their molecular structures.

Hybrid-Ligand Metal-Organic Frameworks Enabling Radio-Radiodynamic-Chemodynamic Therapy Primes Checkpoint Blockade Immunotherapy in Hypoxic Tumors.

Radiodynamic therapy (RDT) offers a potential strategy to enhance radiation therapy (RT) efficacy by efficiently generating singlet oxygen (O) upon radiation. However, both RT and RDT can be compromised by tumor hypoxia. To relieve hypoxia while potentiating RT-RDT, we developed a hybrid-ligand nanoscale metal-organic framework (nMOF), LuMix, for radio-radiodynamic-chemodynamic therapy (RT-RDT-CDT) of tumors with low-dose X-ray.

Porphyrin-based nanoscale metal-organic framework nanocarriers entrapping platinum nanoparticles and S-nitrosoglutathione for sonodynamic therapy in hypoxic tumors.

Sonodynamic therapy (SDT), which employs acoustic energy to generate reactive oxygen species (ROS), has emerged as a promising strategy for tumor treatment. While ultrasound (US) offers deep tissue penetration and minimal invasiveness, the low energy conversion efficiency of sonosensitizers and the hypoxic tumor microenvironment (TME) significantly limit SDT efficacy. To overcome these challenges, we developed a nano-sonosensitizer, TBP-Hf@Pt-GSNO (Hf-Pt-G), composed of a porphyrin-based nanoscale metal-organic framework (nMOF), TBP-Hf, integrated with platinum nanoparticles (Pt NPs) and S-nitrosoglutathione (GSNO).

Mitochondria-targeted photothermal-chemodynamic therapy enhances checkpoint blockade immunotherapy on colon cancer.

Immunotherapy has emerged as a hotspot for cancer treatment. However, the response rate of monotherapy remains relatively low in clinical settings. Photothermal therapy (PTT), which employs light energy to ablate tumors, can also activate tumor-specific immune responses.

Mitochondria-Targeted Nanosystem Enhances Radio-Radiodynamic-Chemodynamic Therapy on Triple Negative Breast Cancer.

Radiodynamic therapy (RDT), which produces O and other reactive oxygen species (ROS) in response to X-rays, can be used in conjunction with radiation therapy (RT) to drastically lower X-ray dosage and reduce radio resistance associated with conventional radiation treatment. However, radiation-radiodynamic therapy (RT-RDT) is still impotent in a hypoxic environment in solid tumors due to its oxygen-dependent nature. Chemodynamic therapy (CDT) can generate reactive oxygen species and O by decomposing HO in hypoxic cells and thus potentiate RT-RDT to achieve synergy.

Visualizing Light-Induced Microstrain and Phase Transition in Lead-Free Perovskites Using Time-Resolved X-Ray Diffraction.

Metal halide perovskites have emerged as promising materials for optoelectronic applications in the last decade. A large amount of effort has been made to investigate the interplay between the crystalline lattice and photoexcited charge carriers as it is vital to their optoelectronic performance. Among them, ultrafast laser spectroscopy has been intensively utilized to explore the charge carrier dynamics of perovskites, from which the local structural information can only be extracted indirectly.

Low-dose X-ray radiotherapy-radiodynamic therapy via nanoscale metal-organic frameworks enhances checkpoint blockade immunotherapy.

Checkpoint blockade immunotherapy relies on energized cytotoxic T cells attacking tumour tissue systemically. However, for many cancers, the reliance on T cell infiltration leads to low response rates. Conversely, radiotherapy has served as a powerful therapy for local tumours over the past 100 years, yet is rarely sufficient to cause systemic tumour rejection.

Nanoscale Metal-Organic Frameworks for Therapeutic, Imaging, and Sensing Applications.

Nanotechnology has played an important role in drug delivery and biomedical imaging over the past two decades. In particular, nanoscale metal-organic frameworks (nMOFs) are emerging as an important class of biomedically relevant nanomaterials due to their high porosity, multifunctionality, and biocompatibility. The high porosity of nMOFs allows for the encapsulation of exceptionally high payloads of therapeutic and/or imaging cargoes while the building blocks-both ligands and the secondary building units (SBUs)-can be utilized to load drugs and/or imaging agents via covalent attachment.

Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy.

Checkpoint blockade immunotherapy enhances systemic antitumor immune response by targeting T cell inhibitory pathways; however, inadequate T cell infiltration has limited its anticancer efficacy. Radiotherapy (RT) has local immunomodulatory effects that can alter the microenvironment of irradiated tumors to synergize with immune checkpoint blockade. However, even with high doses of radiation, RT has rarely elicited systemic immune responses.

Nanoscale Metal-Organic Layers for Deeply Penetrating X-ray-Induced Photodynamic Therapy.

We report the rational design of metal-organic layers (MOLs) that are built from [Hf O (OH) (HCO ) ] secondary building units (SBUs) and Ir[bpy(ppy) ] - or [Ru(bpy) ] -derived tricarboxylate ligands (Hf-BPY-Ir or Hf-BPY-Ru; bpy=2,2'-bipyridine, ppy=2-phenylpyridine) and their applications in X-ray-induced photodynamic therapy (X-PDT) of colon cancer. Heavy Hf atoms in the SBUs efficiently absorb X-rays and transfer energy to Ir[bpy(ppy) ] or [Ru(bpy) ] moieties to induce PDT by generating reactive oxygen species (ROS). The ability of X-rays to penetrate deeply into tissue and efficient ROS diffusion through ultrathin 2D MOLs (ca.

Electron Crystallography Reveals Atomic Structures of Metal-Organic Nanoplates with M(μ-O)(μ-OH)(μ-OH) (M = Zr, Hf) Secondary Building Units.

Nanoscale metal-organic frameworks (nMOFs) have shown tremendous potential in cancer therapy and biomedical imaging. However, their small dimensions present a significant challenge in structure determination by single-crystal X-ray crystallography. We report here the structural determination of nMOFs by rotation electron diffraction (RED).

Chlorin-Based Nanoscale Metal-Organic Framework Systemically Rejects Colorectal Cancers via Synergistic Photodynamic Therapy and Checkpoint Blockade Immunotherapy.

Photodynamic therapy (PDT) can destroy local tumors and minimize normal tissue damage, but is ineffective at eliminating metastases. Checkpoint blockade immunotherapy has enjoyed recent success in the clinic, but only elicits limited rates of systemic antitumor response for most cancers due to insufficient activation of the host immune system. Here we describe a treatment strategy that combines PDT by a new chlorin-based nanoscale metal-organic framework (nMOF), TBC-Hf, and a small-molecule immunotherapy agent that inhibits indoleamine 2,3-dioxygenase (IDO), encapsulated in the nMOF channels to induce systemic antitumor immunity.

Nanoscale Metal-Organic Frameworks for Ratiometric Oxygen Sensing in Live Cells.

We report the design of a phosphorescence/fluorescence dual-emissive nanoscale metal-organic framework (NMOF), R-UiO, as an intracellular oxygen (O2) sensor. R-UiO contains a Pt(II)-porphyrin ligand as an O2-sensitive probe and a Rhodamine-B isothiocyanate ligand as an O2-insensitive reference probe. It exhibits good crystallinity, high stability, and excellent ratiometric luminescence response to O2 partial pressure.

A Chlorin-Based Nanoscale Metal-Organic Framework for Photodynamic Therapy of Colon Cancers.

We report here the rational design of the first chlorin-based nanoscale metal-organic framework (NMOF), DBC-UiO, with much improved photophysical properties over the previously reported porphyrin-based NMOF, DBP-UiO. Reduction of the DBP ligands in DBP-UiO to the DBC ligands in DBC-UiO led to a 13 nm red shift and an 11-fold increase in the extinction coefficient of the lowest-energy Q band. While inheriting the crystallinity, stability, porosity, and nanoplate morphology of DBP-UiO, DBC-UiO sensitizes more efficient (1)O2 generation and exhibits significantly enhanced photodynamic therapy (PDT) efficacy on two colon cancer mouse models as a result of its improved photophysical properties.

Self-assembled nanoscale coordination polymers carrying oxaliplatin and gemcitabine for synergistic combination therapy of pancreatic cancer.

Gemcitabine has long been the standard of care for treating pancreatic ductal adenocarcinoma (PDAC), despite its poor pharmacokinetics/dynamics and rapid development of drug resistance. In this study, we have developed a novel nanoparticle platform based on nanoscale coordination polymer-1 (NCP-1) for simultaneous delivery of two chemotherapeutics, oxaliplatin and gemcitabine monophosphate (GMP), at 30 wt.% and 12 wt.

Nanoscale metal-organic framework for highly effective photodynamic therapy of resistant head and neck cancer.

Photodynamic therapy (PDT) is an effective anticancer procedure that relies on tumor localization of a photosensitizer followed by light activation to generate cytotoxic reactive oxygen species (e.g., (1)O2).

Nanoscale metal-organic frameworks for real-time intracellular pH sensing in live cells.

Real-time measurement of intracellular pH in live cells is of great importance for understanding physiological/pathological processes and developing intracellular drug delivery systems. We report here the first use of nanoscale metal-organic frameworks (NMOFs) for intracellular pH sensing in live cells. Fluorescein isothiocyanate (FITC) was covalently conjugated to a UiO NMOF to afford F-UiO NMOFs with exceptionally high FITC loadings, efficient fluorescence, and excellent ratiometric pH-sensing properties.

Self-assembled nanoscale coordination polymers with trigger release properties for effective anticancer therapy.

Nanoscale coordination polymers (NCPs) are self-assembled from metal ions and organic bridging ligands, and can overcome many drawbacks of existing drug delivery systems by virtue of tunable compositions, sizes and shapes, high drug loadings, ease of surface modification and intrinsic biodegradability. Here we report the self-assembly of zinc bisphosphonate NCPs that carry 48 ± 3 wt% cisplatin prodrug and 45 ± 5 wt% oxaliplatin prodrug. In vivo pharmacokinetic studies in mice show minimal uptake of pegylated NCPs by the mononuclear phagocyte system and excellent blood circulation half-lives of 16.

Synergistic assembly of heavy metal clusters and luminescent organic bridging ligands in metal-organic frameworks for highly efficient X-ray scintillation.

We have designed two metal-organic frameworks (MOFs) to efficiently convert X-ray to visible-light luminescence. The MOFs are constructed from M6(μ3-O)4(μ3-OH)4(carboxylate)12 (M = Hf or Zr) secondary building units (SBUs) and anthracene-based dicarboxylate bridging ligands. The high atomic number of Zr and Hf in the SBUs serves as effective X-ray antenna by absorbing X-ray photons and converting them to fast electrons through the photoelectric effect.

Nanoscale metal-organic frameworks for the co-delivery of cisplatin and pooled siRNAs to enhance therapeutic efficacy in drug-resistant ovarian cancer cells.

Ovarian cancer is the leading cause of death among women with gynecological malignancies. Acquired resistance to chemotherapy is a major limitation for ovarian cancer treatment. We report here the first use of nanoscale metal-organic frameworks (NMOFs) for the co-delivery of cisplatin and pooled small interfering RNAs (siRNAs) to enhance therapeutic efficacy by silencing multiple drug resistance (MDR) genes and resensitizing resistant ovarian cancer cells to cisplatin treatment.

Metal-organic frameworks as sensory materials and imaging agents.

Metal-organic frameworks (MOFs) are a class of hybrid materials self-assembled from organic bridging ligands and metal ion/cluster connecting points. The combination of a variety of organic linkers, metal ions/clusters, and structural motifs can lead to an infinite array of new materials with interesting properties for many applications. In this Forum Article, we discuss the design and applications of MOFs in chemical sensing and biological imaging.