A polydopamine-gated biodegradable cascade nanoreactor for pH-triggered and photothermal-enhanced tumor-specific nanocatalytic therapy.

Despite the great potential of cascade catalytic reactions in tumor treatment, uncontrolled catalytic activities lead to inevitable off-target toxicity to normal tissues, which greatly hampers their clinical conversion. Herein, an intelligent cascade nanoreactor (hMnO-Au@PDA, hMAP) was constructed by depositing glucose oxidase (GOx)-mimicking ultrasmall gold nanoparticles (Au NPs) into honeycomb-shaped manganese oxide (hMnO) nanostructures and then coating them with polydopamine (PDA) to achieve pH-responsive and photothermal-enhanced nanocatalytic therapy. Upon exposure to the mild acidic tumor microenvironment (TME), the PDA gatekeeper would collapse, and the inner hMnO could simultaneously deplete glutathione (GSH) and generate Mn, while a considerable amount of HO produced from the oxidation of glucose by GOx-mimicking Au NPs could accelerate the Mn-mediated Fenton-like reaction, yielding sufficient highly toxic ˙OH.

Small-Molecule-Selective Organosilica Nanoreactors for Copper-Catalyzed Azide-Alkyne Cycloaddition Reactions in Cellular and Living Systems.

We reported the synthesis of a tris(triazolylmethyl)amine (TTA)-bridged organosilane, functioning as Cu(I)-stabilizing ligands, and the installation of this building block into the backbone of mesoporous organosilica nanoparticles (TTASi) by a sol-gel way. Upon coordinating with Cu(I), the mesoporous Cu-TTASi, with a restricted metal active center inside the pore, functions as a molecular-sieve-typed nanoreactor to efficiently perform Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reactions on small-molecule substrates but fails to work on macromolecules larger than the pore diameter. As a proof of concept, we witnessed the advantages of selective nanoreactors in screening protein substrates for small molecules.

Dual catalytic cascaded nanoplatform for photo/chemodynamic/starvation synergistic therapy.

In this study, manganese dioxide (MnO) was attached to prussian blue (PB) by a one-pot method to prepare PBMO. Then, the GOD was loaded onto PBMO through the electrostatic interaction of hyaluronic acid (HA) to form tumor-targeted nanoplatform (PBMO-GH). Hydrogen peroxide (HO) and gluconic acid were produced through the GOD-catalyzed enzymatic reaction.

Mesoporous Silica-Coated Silver Nanoframes as Drug-Delivery Vehicles for Chemo/Starvation/Metal Ion Multimodality Therapy.

Cutting off the energy supply by glucose oxidase (GOx) to starve cancer cells has been a feasible and efficient oncotherapy strategy. The employment of GOx can effectively starve tumor cells by aerobic hydrolysis of glucose hopefully strengthening the abnormality (including the decrease in pH, the increase of hypoxia, and toxic hydrogen peroxide) in the tumor microenvironment (TME). On this basis, we designed and fabricated a GOx-conjugated yolk-shell Ag@mSiO nanoframe with Ag NPs and GOx-conjugated mesoporous silica as the yolk and the shell, respectively, to make full use of changes the GOx induces in TME.

A CD44-targeted Cu(ii) delivery 2D nanoplatform for sensitized disulfiram chemotherapy to triple-negative breast cancer.

Recent studies have suggested that the anticancer activity of disulfiram (DSF, an FDA-approved alcohol-abuse drug) is Cu-dependent. Low system toxicity and explicit pharmacokinetic characteristics of DSF necessitate safe and effective Cu supplementation in local lesion for further applications. Herein, we presented a new conceptual 'nanosized coordination transport' strategy of Cu(ii) that was realized in porphyrin-based metal-organic frameworks, Sm-TCPP, with strong binding ability to Cu(ii) due to their coordination interactions.

Photothermal-reinforced and glutathione-triggered in Situ cascaded nanocatalytic therapy.

Tumor microenvironment (TME)-responsive nanoformulations that catalyze a cascade of intracellular redox reactions showed promise for tumor treatment with high specificity and efficiency. In this study, we report Cu-doped zeolitic imidazolate frameworks-coated polydopamine nanoparticles (PDA@Cu/ZIF-8 NPs) for glutathione-triggered and photothermal-reinforced sequential catalytic therapy against breast cancer. In the TME, the PDA@Cu/ZIF-8 NPs could initially react with antioxidant glutathione (GSH), inducing GSH depletion and Cu generation.

A novel versatile yolk-shell nanosystem based on NIR-elevated drug release and GSH depletion-enhanced Fenton-like reaction for synergistic cancer therapy.

In this study, a versatile doxorubicin (DOX)-loaded yolk-shell nano-particles (HMCMD) assembled with manganese dioxide (MnO) as the core and copper sulfide (HMCuS) as the mesoporous (∼ 6.4 nm) shell, was designed and synthesized. The resulting HMCMD possess excellent photothermal conversion efficiency.

Biomimetic Platinum Nanozyme Immobilized on 2D Metal-Organic Frameworks for Mitochondrion-Targeting and Oxygen Self-Supply Photodynamic Therapy.

Photodynamic therapy (PDT) as a noninvasive therapy mode has attracted considerable attention in the field of oncotherapy. However, the PDT efficacy is restricted either by the tumor hypoxia environment or the inherent properties of photosensitizers (PSs) including bad water solution, photobleaching, and easy aggregation. Herein, we designed and synthesized a new two-dimensional (2D) metal-organic framework, Sm-tetrakis(4-carboxyphenyl)porphyrin (TCPP) nanosheets, by assembling transition metal ions (Sm) and PSs (TCPP), on which the catalase (CAT)-mimicking platinum nanozymes were then in situ grown for sufficient oxygen supply during PDT.

Hypoxia-augmented and photothermally-enhanced ferroptotic therapy with high specificity and efficiency.

The rigorous reaction conditions (sufficient HO and a low pH value) of an efficient Fenton reaction limit its further biomedical translation. Therefore, it is urgent to improve the efficacy of the Fenton reaction at the tumor site for efficient ferroptotic therapy. Herein, a hypoxia-responsive-Azo-BSA functionalized biomimetic nanoreactor (Fe(iii)-GA/GOx@ZIF-Azo), encapsulating ultrasmall ferric-gallic acid coordination polymer nanoparticles (Fe(iii)-GA) and glucose oxidase (GOx) into a zeolitic imidazolate framework (ZIF), was constructed for tumor ablation through an intensive Fenton reaction accelerated by not only sustained Fe and HO supply but also low pH and photothermal stimulation.

A small-sized and stable 2D metal-organic framework: a functional nanoplatform for effective photodynamic therapy.

The efficiency of photosensitizers in tumor photodynamic therapy (PDT) often compromises their poor water solubility, low extinction coefficients, photobleaching, and dissatisfactory reactive oxygen species (ROS) generation efficiency. Herein, a nanoscale 2D metal-organic framework, Sm-HTCPP nanosheets, was first synthesized by Sm-driven coordination with a porphyrin derivative (tetrakis(4-carboxyphenyl)porphyrin (HTCPP)) for highly effective PDT of breast cancer. The prepared Sm-HTCPP possessed nanoplate morphology with ultrathin thickness at the sub-10 nm level and an ultrasmall plane size at the sub-100 nm level.

Photothermal-Enhanced Inactivation of Glutathione Peroxidase for Ferroptosis Sensitized by an Autophagy Promotor.

Until now, ferroptotic therapeutic strategies remain simple, although ferroptosis has aroused extensive interest owing to its escape from the biocarriers of conventional therapeutic modalities. Herein, we construct a photothermal (PT)- and autophagy-enhanced ferroptotic therapeutic modality based on MnO@HMCuS nanocomposites (HMCMs) for efficient tumor ablation. The HMCMs possess PT-enhanced glutathione (GSH) depletion capability, thereby inducing PT-enhanced ferroptosis via the reinforced inactivation of glutathione peroxidase 4 (GPX4).

Enhanced cellular uptake of near-infrared triggered targeted nanoparticles by cell-penetrating peptide TAT for combined chemo/photothermal/photodynamic therapy.

Recently, the emergence of cell-penetrating peptides (CPPs) like TAT has greatly improved the efficiency of cancer therapy by enhancing cellular uptake of nanomaterials. Here, we designed a near-infrared (NIR) triggered TAT-based targeted nanoplatform (cRGD@TAT-DINPs), which co-delivered anticancer drug doxorubicin (DOX) and biocompatible dye indocyanine green (ICG) to realize combined chemo/photothermal/photodynamic therapy of cancer in vitro. The resulting nanoparticles showed favorable monodispersity and colloidal stability.

Cisplatin and Ce6 loaded polyaniline nanoparticles: An efficient near-infrared light mediated synergistic therapeutic agent.

Lipid-polymer hybrid nanoparticle was suggested to be a new and promising drug delivery agent due to the suitable particle size and controllable release. However, the low drug loading capacity has been a critical problem in the improvement of the nano-carrier systems. At present work, we have designed and developed smart nanoparticles with cholesterol-cisplatin (IV) conjugate contained to enhance the drug loading capacity.

Enhanced highly toxic reactive oxygen species levels from iron oxide core-shell mesoporous silica nanocarrier-mediated Fenton reactions for cancer therapy.

In this study, iron oxide core-shell mesoporous silica nanoparticles (FeO@MSN) were prepared via the hydrolysis of tetraethyl orthosilicate on the surfaces of FeO nanoparticles, and these were further conjugated with folate (PEG-FA) and mitochondrial targeting triphenylphosphonium (TPP) to form FeO@MSN-TPP/PEG-FA. A reactive oxygen species (ROS) promoting synergistic combined chemotherapy platform was designed through FeO@MSN-TPP/PEG-FA encapsulating doxorubicin (DOX) and 3-amino-1,2,4-triazole (AT) for cancer therapy. DOX could stimulate the activation of nicotinamide adenine dinucleotide phosphate oxidases (NOXs), which change oxygen into superoxide radicals, which could be further triggered to produce hydrogen peroxide (HO) using the superoxide dismutase (SOD) enzyme.

Decoration of Cisplatin on 2D Metal-Organic Frameworks for Enhanced Anticancer Effects through Highly Increased Reactive Oxygen Species Generation.

Herein, a biocompatible 2D metal-organic frameworks (Cu-TCPP(Fe)) based on TCPP(M) (TCPP = tetrakis (4-carboxyphenyl) porphyrin, M = Fe) and copper ion were synthesized as a novel drug carrier. Sequentially, the cisplatin was loaded on the merge of carboxyl-rich Cu-TCPP(Fe) through forming favorable carboxyl-drug interactions. The prepared Pt/Cu-TCPP(Fe) showed highly enhanced cytotoxicity than that of free cisplatin in human pulmonary carcinoma A549 cells, whereas inverse inhibitory effects were observed in human normal BEAS-2B cells.

Iron Oxide Nanocarrier-Mediated Combination Therapy of Cisplatin and Artemisinin for Combating Drug Resistance through Highly Increased Toxic Reactive Oxygen Species Generation.

Combination therapy with multiple drugs through a multi-pronged assault as a strategy to combat cisplatin resistance shows great potential in biochemical therapy for cancer. However, inherent issues such as low drug loading and the poor synergistic effects of multiple drugs partially limit the further application of combination therapy. Here, we synthesized a new compound, ART-Chol, by coupling artemisinin and cholesterol as a base material combined with cyclic (Arg-Gly-Asp-d-Phe-Lys)]-poly(ethylene glycol) distearoylphosphatidylcholine (cRGD-PEG-DSPE) and phospholipids to form a magnetic liposome cRGD-AFePt@NPs encapsulating superparamagnetic ferric oxide nanoparticles and cisplatin for achieving high drug loading and a better synergistic effect.

Single-Layered Two-Dimensional Metal-Organic Framework Nanosheets as an in Situ Visual Test Paper for Solvents.

Through a facile-operating ultrasonic force-assisted liquid exfoliation technology, the single-layered two-dimensional (2D) [Co(CNS)(pyz)] (pyz = pyrazine) nanosheets, with a thickness of sub-1.0 nm, have been prepared from the bulk precursors. The atomically thickness and the presence of abundant sulfur atoms with high electronegativity arrayed on the double surfaces of the sheets are making this kind of 2D MOF (metal-organic framework) nanosheets highly sensitive to intermolecular interactions.

Near infrared radiated stimulus-responsive liposomes based on photothermal conversion as drug carriers for co-delivery of CJM126 and cisplatin.

Synergistic therapy has caused increasing interest in recent treatment of cancer owing to its preferable therapeutic efficiency to most single antineoplastic protocol. Herein, we design a co-delivery two drugs nanosystem based on biodegradable liposomes, loading cisplatin, Indocyanine green (ICG), and CJM126 coupled with cholesterol derivative (CJM-Chol) for the purpose of synergistic therapy. The obtained nanoparticles showed a uniform diameter of 103.