Photoredox-Cobaloxime Catalysis for Selective Oxidative Dehydrogenative [4+2] Annulation of Imidazo-Fused Heterocycles with Alkenes.

A selective oxidative [4+2] annulation of alkenes with imidazo-fused heterocycles has been developed by using the synergistic combination of photoredox and cobaloxime catalysts. It allows facile access to various imidazole-fused polyaromatic scaffolds accompanied by H2 evolution. This protocol features high regioselectivity as well as a broad substrate scope. Detailed mechanistic studies indicate that twice the electron/H transfer processes facilitated by this catalytic system achieve the annulation π-extension of imidazo-fused heterocycles with alkenes.

NIR-Induced Disintegration of CuS-Loaded Nanogels for Improved Tumor Penetration and Enhanced Anticancer Therapy.

Nanocarrier-based cancer therapy suffers from poor tumor penetration and unsatisfied therapeutical efficacy, as its vascular extravasation efficiency is often compromised by the intrinsic physiological heterogeneity in tumor tissues. In this work, novel near infrared (NIR)-responsive CuS-loaded nanogels are prepared to deliver anticarcinogen into the tumor. These hybrid polymeric nanogels possess high photothermal conversion efficiency, and are able to load a large amount of antitumor drug (e.g., doxorubicin [DOX]). More importantly, the thermal heat could induce self-destruction of the big-size framework of hybrid nanogels into small nanoparticles, which greatly facilitates tumor penetration to release DOX deep inside the tumor, as validated by photoacoustic (PA) imaging which exhibits 26.3 times enhancement at the interior region compared to signals of groups without laser irradiation. Such structural alteration, combined with strong photothermal and chemotherapy effects, leads to remarkable inhibition of tumor growth in mice. As a result, this NIR-induced disintegration of CuS-loaded nanogels provides a novel drug delivery strategy and might open a new window for clinical cancer treatment.

Cyclomatrix Polyphosphazene Porous Networks with J-Aggregated Multiphthalocyanine Arrays for Dual-Modality Near-Infrared Photosensitizers.

Here, we have developed a kind of cyclomatrix polyphosphazene with excellent photophysical properties and pursued their potential of being organic photosensitizers for dual-modality phototherapy. Briefly, hexachlorocyclophosphazene (HCCP) with D3 h symmetry is adopted as a synthon to attach Zn(II) phthalocyanine (ZnPc) to form dendritic units that are covalently expanded into a soluble porous network through the nucleophilic substitution reaction. Molecular simulation reveals that the multi-ZnPc units around HCCP can be oriented in a side-by-side manner, leading to the remarkably red-shifted and intense absorbance in the near-infrared (NIR) region. To validate the potential in bioapplication, such ZnPc-based polyphosphazenes are assembled by incorporation of polyvinylpyrrolidone (PVP) to produce the uniform nanoparticles with aqueous dispersibility and biocompatibility. From the in vitro results, the PVP-stabilized photosensitizing nanoparticles can undergo the photothermal/photodynamic processes to concurrently generate heat and singlet oxygen for efficiently killing cancer cells upon exposure to a single-bandwidth NIR laser (785 nm). Compared with the known organic photosensitizers, cyclomatrix polyphosphazene would be a promising platform to configure a diversity of reticular arrays with dense and oriented arrangement of dye molecules, leading to their largely enhanced photophysical and photochemical properties.

Localized Fe(II)-Induced Cytotoxic Reactive Oxygen Species Generating Nanosystem for Enhanced Anticancer Therapy.

The anticancer therapy on the basis of reactive oxygen species (ROS)-mediated cellular apoptosis has achieved great progress. However, this kind of theraputic strategy still faces some challenges such as light, photosensitizer and oxygen (O2) dependence. In this article, a ROS-mediated anticancer therapy independent of light, photosensitizer and oxygen was established based on a Fe2+-induced ROS-generating nanosystem. First, artemisinin (ART) was loaded in porous magnetic supraparticles (MSP) by a nanodeposition method. Then, the poly(aspartic acid)-based polymer, which consisted of dopamine, indocyanine green, and polyethylene glycol side chain, was coated onto the surface of ART-loaded MSP. When the nanoparticles entered into cancer cells, a reaction of Fe2+-mediated cleavage of the endoperoxide bridge contained in ART occurred and subsequent a large amount of ROS was generated. Moreover, a NIR light was used to effectively increase the local temperature of tumor in virtue of the superior photothermal effects of MSP, which enabled us to accelerate the ROS generation and achieved an enhanced ROS yield. The newly developed nanodrug system displayed a high level of intracellular ROS generation, leading to the desired killing efficacy against malignant cells and solid tumor. This smart nanosystem holds great potential to overcome the existing barrier in PDT and opens a promising avenue for anticancer therapy.

Supermolecular theranostic capsules for pH-sensitive magnetic resonance imaging and multi-responsive drug delivery.

Magnetite (Fe3O4) microcapsules prepared by layer-by-layer self-assembly are investigated as multi-functional magnetic resonance imaging contrast agents and drug carriers. They are produced by host-guest interactions and Coulombic force from different supramolecular polymers. Drug molecules are released controllably from the microcapsules by non-invasive ultra-violet light induced photo-isomerization of the azobenzene molecule and pH sensitive Schiff's base. In addition, by encapsulation of the superparamagnetic iron oxide nanoparticles (SPION) in the nearby layers, magnetic field targeting and MRI contrast are achieved. Under tumor-like acidic conditions (pH = 5.6), the r2 relaxivity of the microcapsules is 126 mM-1 s-1 which is 37% higher than that in a neutral environment (92 mM-1 s-1). As a result of the low pH enhanced MRI contrast agent, the tumor structure can be observed clearly in vivo confirming the high efficacy as a negative MRI agent in T2-weighted imaging. The materials as combined carriers have great potential in clinical applications as drug delivery agents and contrast agents in MRI.