A Covalent Organic Framework Derived N-doped Carbon Nanozyme as the All-rounder for Targeted Catalytic Therapy and NIR-II Photothermal Therapy of Cancer.

Nanomaterials with intrinsic enzyme-like activities (nanozymes) have gained significant attention in cancer catalytic therapy; however, developing metal-free nanozymes with multivariant enzyme-like activity as the "all-rounder" for cancer therapy remains challenging. Herein, a covalent organic framework (COF) derived carbon-based nanozyme is rationally devised to achieve synergistic catalytic therapy and second near-infrared (NIR-II) photothermal therapy of cancer. The developed nanozyme possesses multivariant enzyme-like activities, including oxidase (OXD)-like, catalase (CAT)-like, and peroxidase (POD)-like catalytic activities, which enables the nanozyme to produce adequate reactive oxygen species (ROS) for cancer cell killing. Furthermore, the nanozyme showed excellent photothermal converting activity that could kill cancer cells upon NIR-II laser irradiation, owing to the strong NIR-II absorption capacity of carbon-based materials. It is also worth noting that the nanozyme exhibited cytotoxicity specifically in tumor tissue profiting from the discrepant H2O2 level between tumor and normal tissue and the spatiotemporal controllability of laser irradiation. This work may inspire further development of intelligent nanozymes in biological applications across broad therapeutic and biomedical fields.

GSH-Triggered NO releasing nanoplatform based on a covalent organic framework for "1 + 1 > 2" synergistic cancer therapy.

A porphyrin containing covalent organic framework (COF) was developed as the glutathione responsive nitric oxide (NO) donor delivery nanoplatform for "1 + 1 > 2" synergistic cancer therapy of NO mediated therapy and photodynamic therapy.

Sustained-release nanocapsule based on a 3D COF for long-term enzyme prodrug therapy of cancer.

A well-designed three-dimensional (3D) covalent organic framework (COF) was constructed as a nanocapsule for the encapsulation of horseradish peroxidase (HRP), which could realize sustained release of HRP to prolong the duration of the therapeutic agents and promote long-term enzyme prodrug therapy.

Covalent Organic Framework-Derived Carbonous Nanoprobes for Cancer Cell Imaging.

Covalent organic frameworks (COFs) have emerged as promising materials for biomedical applications, but their functions remain to be explored and the potential toxicity concerns should be resolved. Herein, it is presented that carbonization significantly enhances the fluorescence quenching efficiency and aqueous stability of nanoscale COFs. The probes prepared by physisorbing dye-labeled nucleic acid recognition sequences onto the carbonized COF nanoparticles (termed C-COF) were employed for cell imaging, which could effectively light up biomarkers (survivin and TK1 mRNA) in living cells. The C-COF has enhanced photothermal conversion capacity, indicating that the probes are also promising candidates for photothermal therapy. The potential toxicity concern from the aromatic rigid building units of COFs was detoured by carbonization. Overall, carbonization is a promising strategy for developing biocompatible and multifunctional COF-derived nanoprobes for biomedical applications. This work may inspire more versatile COF-derived nanoprobes for bioanalysis and nanomedicine.

Selenium-engineered covalent organic frameworks for high-efficiency and long-acting cancer therapy.

A porphyrin-containing covalent organic framework (COF) was synthesized as a substrate for decorating selenium nanoparticles (Se NPs) via in situ reduction. Se NP-mediated therapy (SeT) was carried out in conjunction with photodynamic therapy (PDT) to provide an increased anticancer effect and remedy the constrained efficacy of PDT.

An enzyme nanopocket based on covalent organic frameworks for long-term starvation therapy and enhanced photodynamic therapy of cancer.

An enzyme nanopocket constructed from a porphyrin-based covalent organic framework (COF) was developed to co-load glucose oxidase (GOx) and catalase (CAT) for long-term starvation therapy and enhanced photodynamic therapy (PDT).

A COF-based anti-interference nanoplatform for intracellular nucleic acid imaging.

We demonstrate here that a porphyrin covalent organic framework-based nanoplatform could effectively avoid the interference of proteins and biothiols and result in high-fidelity signals in intracellular mRNA imaging.

A COF-based nanoplatform for highly efficient cancer diagnosis, photodynamic therapy and prognosis.

Covalent organic frameworks (COFs) have emerged as a kind of promising material for analytical and biomedical purposes. However, simultaneous cancer diagnosis and therapy with COFs remain a challenge. We report here a COF-based theranostic nanoplatform by integrating a dye-labeled oligonucleotide onto porphyrin-based COF nanoparticles for highly efficient cancer diagnosis and therapy. The fluorescence of the dye was effectively quenched by the COF through fluorescence resonance energy transfer (FRET). In the presence of biomarker survivin mRNA, more stable duplexes were formed and separated from the COF NPs, enabling the recovery of the fluorescence signal and selective cancer imaging. Under NIR laser irradiation, COF NPs generated abundant reactive oxygen species (ROS) to induce cancer cell apoptosis owing to their crystalline reticular structure. In vitro and in vivo experiments revealed that the nanoplatform has a high specificity and inhibition effect toward cancer cells and solid tumors. Interestingly, prognostic evaluation was also realized with COF-survivin. This work will offer new insights into COF-based probes and inspire the development of more versatile tools for biomedical applications.

Tumor-Targeted Cascade Nanoreactor Based on Metal-Organic Frameworks for Synergistic Ferroptosis-Starvation Anticancer Therapy.

Although ferroptosis therapy has been proven to be a promising strategy for cancer treatment, its efficacy still might be limited by insufficient H2O2 supply in tumor tissue. Herein, we designed a cancer cell membrane-cloaked cascade nanoreactor based on ferric metal-organic frameworks (MOF) and glucose oxidase (GOx) decoration for synergistic ferroptosis-starvation anticancer therapy. The GOx can catalyze glucose to generate sufficient H2O2 for ferroptosis therapy, and the glucose consumption caused by GOx can be utilized as another attractive cancer treatment strategy called starvation therapy. When the nanoreactor reached tumor sites, high concentration of GSH reduced Fe3+ to trigger structure collapse of MOF and release Fe2+ and GOx catalyzed the oxidation of glucose to generate H2O2. Then Fenton reaction happened between H2O2 and Fe2+ to produce hydroxyl radicals (•OH) and promoted ferroptosis therapy. With these cascade reactions, the synergistic ferroptosis-starvation anticancer therapy was realized. Furthermore, the cancer cell membrane endows the nanoreactor homologous targeting and immune escaping ability, which facilitated the nanoreactor to accumulate into tumor site with high efficiency. The nanoreactor exhibits high efficiency for tumor suppression with the in situ consumed and produced compounds, which can promote the development of precise cooperative cancer therapy with spatiotemporal controllability.

Rapid Preparation of Au-Se-Peptide Nanoprobe Based on a Freezing Method for Bioimaging.

Fluorescent nanoprobes based on peptide-functionalized gold nanoparticles (AuNPs) have been widely used in bioassays. The Au-Se bond is considered as a better candidate than the Au-S bond to link the peptides and AuNPs due to the stronger ability against interference of intracellular thiol. However, the current synthetic methods for preparing peptide/AuNPs nanoprobes are always complex and time-consuming. Developing a convenient and rapid method to synthesize the Au-Se bond based nanoprobes is expected to further facilitate their application in fundamental research. Herein, we present a facile and rapid approach to prepare the Au-Se-peptide nanoprobes through a direct freezing process, which is easy-to-operate, time-saving, and surfactant-free. Compared with the traditional method, the amount of peptide loaded on AuNPs by freezing method is also promoted with 20-30%. Furthermore, the obtained nanoprobe was successfully applied to identify autophagy and apoptosis in chemotherapeutic drug treated cancer cells.

Programmed Release of Dihydroartemisinin for Synergistic Cancer Therapy Using a CaCO3 Mineralized Metal-Organic Framework.

Dihydroartemisinin (DHA) has attracted increasing attention as an anticancer agent. However, using DHA to treat cancer usually depends on the synergistic effects of exogenous components, and the loss of DHA during delivery reduces its effectiveness in cancer therapy. Reported herein is a programmed release nanoplatform of DHA to synergistically treat cancer with a Fe-TCPP [(4,4,4,4-(porphine-5,10,15,20-tetrayl) tetrakis(benzoic acid)] NMOF (nanoscale MOF) having a CaCO3 mineralized coating, which prevents DHA leakage during transport in the bloodstream. When the nanoplatform arrives at the tumor site, the weakly acidic microenvironment and high concentration of glutathione (GSH) trigger DHA release and TCPP activation, enabling the synergistic Fe2+ -DHA-mediated chemodynamic therapy, Ca2+ -DHA-mediated oncosis therapy, and TCPP-mediated photodynamic therapy. In vivo experiments demonstrated that the nanoplatform showed enhanced anticancer efficiency and negligible toxicity.

Catalase-like metal-organic framework nanoparticles to enhance radiotherapy in hypoxic cancer and prevent cancer recurrence.

Tumor hypoxia typically occurs inside a solid tumor with an inadequate oxygen supply, sharply reducing the therapeutic efficiency of radiotherapy and significantly increasing the risk of local tumor recurrence. Herein, we designed folic acid modified enzyme-like hafnium-based manganoporphyrin metal-organic framework nanoparticles (MnTCPP-Hf-FA MOF NPs) to overcome hypoxia-induced radioresistance and prevent postoperative recurrence. Hf, a high-Z element, can effectively absorb X-ray energy and convert O2 and H2O into reactive oxygen species to induce cell apoptosis. The MnTCPP ligand has an enzyme-like ability to catalytically decompose endogenous H2O2 into O2 for enhancing RT in hypoxic tumors. In vivo experiments revealed that the MOF NPs could effectively inhibit melanoma growth and prevent tumor postoperative recurrence with only one X-ray irradiation after intravenous injection. We expect that the current study provides a versatile approach for solving the critical radioresistance issue of hypoxic tumors.

Ratiometric Fluorescent Quantification of the Size-Dependent Cellular Toxicity of Silica Nanoparticles.

Nanoscale particles are ubiquitous in the atmosphere, and the widespread use of nanoparticles may increase the risks of organ damage. Therefore, it is of great significance to investigate the toxicity of nanoparticles of different sizes toward living cells, especially lung epithelial cells. In this study, the quantitative ratiometric fluorescent detection of intracellular pH changes was utilized to evaluate the cytotoxicity of mesoporous silica nanoparticles of different sizes after the nanoparticles had entered lung epithelial cells. The results showed that, with decreasing nanoparticle size, the intracellular reactive oxygen species (ROS) concentration increased and the intracellular pH value decreased; consequently, this led to the enhanced cytotoxicity of the nanoparticles. Notably, no obvious cytotoxicity was induced by the nanoparticles when the size of the nanoparticles was larger than 135 nm. The presented strategy of using ratiometric fluorescent detection of intracellular pH to quantify the size-dependent cellular toxicity of nanoparticles provides a novel approach for investigating the cytotoxicity of nanomaterials.

Hydrogen bond directed aerobic oxidation of amines via photoredox catalysis.

An application of H-bonding interactions for directing the α-C-H oxidation of amines to amides and amino-ketones catalyzed by an organic photocatalyst is reported. The high efficiency of this method is demonstrated by the aerobic oxidation of pyrrolidines, diarylamines and benzylamines bearing urea groups with high yields and a wide substrate scope.

Nuclear-Targeted Photothermal Therapy Prevents Cancer Recurrence with Near-Infrared Triggered Copper Sulfide Nanoparticles.

Clinical cancer treatments nowadays still face the challenge of recurrence due to the residual cancer cells and minute lesions in surgeries or chemotherapies. To effectively address the problem, we introduce a strategy for constructing cancer cell nuclear-targeted copper sulfide nanoparticles (NPs) with a significant photothermal effect to completely kill residual cancer cells and prevent local cancer recurrence. The NPs could directly target the tumor cells and further enter the nucleus by the surface modification of RGD and TAT peptides. Under the irradiation of 980 nm near-infrared laser, the NPs rapidly increase the temperature of the nucleus, destroy the genetic substances, and ultimately lead to an exhaustive apoptosis of the cancer cells. In vivo experiments show that the designed NPs could effectively treat cancer and prevent the return of cancer with a single laser irradiation for 5 min. The photothermal therapy strategy with nuclear targeting for cancer therapy and anti-recurrence will provide more possibilities to develop efficient platforms for treating cancer.

A pre-protective strategy for precise tumor targeting and efficient photodynamic therapy with a switchable DNA/upconversion nanocomposite.

Tumor-specific targeting based on folic acid (FA) is one of the most common and significant approaches in cancer therapy. However, the expression of folate receptors (FRs) in normal tissues will lead to unexpected targeting and unsatisfactory therapeutic effect. To address this issue, we develop a pre-protective strategy for precise tumor targeting and efficient photodynamic therapy (PDT) using a switchable DNA/upconversion nanocomposite, which can be triggered in the acidic tumor microenvironment. The DNA/upconversion nanocomposite is composed of polyacrylic acid (PAA) coated upconversion nanoparticles (UCNPs), the surface of which is modified using FA and chlorin e6 (Ce6) functionalized DNA sequences with different lengths. Initially, FA on the shorter DNA was protected by a longer DNA to prevent the bonding to FRs on normal cells. Once reaching the acidic tumor microenvironment, C base-rich longer DNA forms a C-quadruplex, resulting in the exposure of the FA groups and the bonding of FA and FRs on cancer cell membranes to achieve precise targeting. Simultaneously, the photosensitizer chlorin e6 (Ce6) gets close to the surface of UCNPs, enabling the excitation of Ce6 to generate singlet oxygen (1O2) under near infrared light via Förster resonance energy transfer (FRET). In vivo experiments indicated that higher tumor targeting efficiency was achieved and the tumor growth was greatly inhibited through the pre-protective strategy.

A cyano-bridged Cu(i)-based organic framework coupled with the C-C bond cleavage of acetonitrile for selective and sensitive sensing of Fe3+ ions.

A cyano-bridged Cu(i) organic framework based on [Cu6(CN)6]n was synthesized, in which cyano anions were generated in situ from the C-C bond cleavage of acetonitrile. The as-synthesized compound displays orange-red luminescence and is further proven to be a promising Fe3+ luminescent sensor with high selectivity and sensitivity.

Visualizing Breast Cancer Cell Proliferation and Invasion for Assessing Drug Efficacy with a Fluorescent Nanoprobe.

Hard-to-treat cancers are closely relative to uncontrolled cell proliferation, invasion, and metastasis. Assessing proliferation and invasion properties of tumor cells both in vitro and in vivo is especially important for acquiring reliable information for cancer pathogenesis, drug screening, and therapeutic effect evaluation. Herein, we developed a multicolor fluorescent nanoprobe for simultaneously monitoring breast cancer cells' proliferation marker Ki-67 and invasion marker urokinase plasminogen activator (uPA). After treated with the anticancer drugs tamoxifen and curcumin, the changes in cancer cell proliferation and invasion properties were visually detected and therapeutic effects of corresponding drugs were further assessed in vitro and in vivo. The design of the fluorescent nanoprobe opens up an avenue for investigating unscheduled proliferation, invasion, and metastasis in living cells and in vivo and as such will be a promising tool to screen antitumor drugs and evaluate drug efficiency in an extremely efficient manner.

Conformation driven in situ interlock: from discrete metallocycles to infinite polycatenanes.

A novel conformation driven self-assembly system, where four metallocycles with different conformations have been in situ self-assembled, has been reported. Interestingly, only square metallocycles can further interlock into polycatenanes. However, rectangular and rhombus metallocycles fail to overcome such an entropically unfavourable process, which constitutes an obstacle to the formation of polycatenanes.