Xiaogang Qu

Accurate regulation of cellular zinc signaling is imperative to decipher underlying zinc functions and develop new therapeutic agents. However, the ability to modulate zinc in a spatiotemporal manner remains elusive. We herein report an intelligent spiropyran-upconversion (SP-UCNPs) based nanosystem that enables near-infrared (NIR) light-controlled zinc release at precise times and locations. The magnitude of zinc release can be simply manipulated by varying the duration of NIR irradiation. Moreover, the utilization of NIR light not only showed little damage to cells but also significantly improved penetration depth. By evaluating activity of a model protein, phosphatase 2A, we further validated zinc signaling activation. Importantly, our strategy may be broadly applicable to other types of metal ions, like the ubiquitous second messenger calcium. More importantly, our strategy can potentially enable the precise control of specific signaling pathways of metal ions while minimizing cellular damage, facilitating the advanced manipulation of cellular dynamics. Open image in new window

Artificial hyperthermia is an emerging technique to induce apoptotic cancer cell death. However, achieving effective hyperthermic apoptosis is often difficult, as cells typically acquire resistance to thermal stress. With the aid of sequential irradiation, highly integrated nanoassemblies based on reduced graphene oxide–ZnO nanoparticles–hyaluronic acid (rGo‐ZnO‐HA) can serve as a multi‐synergistic platform for targeted high‐performance apoptotic cancer therapy. The surface engineering of ZnO/graphene hybrid with multifunctional HA biomacromolecules simultaneously confers the system colloidal stability, biocompatibility, and a cancer cell targeting ability. After receptor‐mediated endocytosis, enzyme‐mediated fluorescence activation helps track cellular uptake and provides truly molecular imaging. Furthermore, the reactive oxygen species (ROS) generated by ZnO/rGo under light illumination can effectively sensitize cancer cells to the subsequent NIR laser‐induced apoptotic hyperthermia. In particular, photo modulation of cellular ROS to sensitize cells provides a novel approach to increase the efficacy of hyperthermic apoptosis. These findings suggest that a powerful apoptotic therapeutic platform could be achieved based on the multi‐synergistic platform.

An active cell scaffold based on a graphene–polymer hydrogel has been successfully fabricated. The macroporous hydrogel can efficiently capture cells not only through the bioadhesive ligand RGD but also through on-demand release of cells with an NIR light stimulus. The latter process shows better dynamic control over cells than traditional passive-hydrogel-based cell depots.

A facile one‐pot synthesis of fluorescent AuNCs by using ovalbumin‐CpG oligodeoxynucleotides (ODNs) conjugates as the templates, which can elicit specific immunological responses, is demonstrated. Through dual‐delivery of protein antigen and CpG ODNs, the as‐prepared AuNCs can act as smart self‐vaccines to assist in generation of high immunostimulatory activity while simultaneously act as an imaging agent. The AuNCs‐based vaccines are not thought to have not been reported so far, making this platform the first example of the usage of AuNCs as effective vaccines. Furthermore, compared with the antigen, the immunostimulatory activity of the as‐prepared AuNCs can not only be retained, but also can be effectively enhanced. These findings suggest the AuNCs‐based vaccines may be utilized as safe and efficient immunostimulatory agents that are able to prevent and/or treat a variety of ailments.

Herein, we report a new kind of highly fluorescent probe for Cu²⁺ sensing generated by hydrothermal treatment of graphene quantum dots (GQDs). After hydrothermal treatment in ammonia, the greenish‐yellow fluorescent GQDs (gGQDs) with a low quantum yield (QY, 2.5 %) are converted to amino‐functionalized GQDs (afGQDs) with a high QY (16.4 %). Due to the fact that Cu²⁺ ions have a higher binding affinity and faster chelating kinetics with N and O on the surface of afGQDs than other transition‐metal ions, the selectivity of afGQDs for Cu²⁺ is much higher than that of gGQDs. Furthermore, afGQDs are biocompatible and eco‐friendly, and the afGQDs with a positive charge can be easily taken up by cells, which makes it possible to sense Cu²⁺ in living cells. The strategy presented here is simple in design, economical, and offers a “mix‐and‐detect” protocol without dye‐modified oligonucleotides or complex chemical modification.

We demonstrate for the first time that PPy–SiO₂–GTA composites can be used as efficient photothermal agents for killing pathogenic bacteria under NIR irradiation. The cell growth of both gram-positive and gram-negative bacteria targeted by PPy–SiO₂–GTA composites could be inhibited effectively after photothermal treatment.

Upconversion nanoparticles (UCNPs) have been proposed as a promising new class of biological luminescent labels because of their weak auto‐fluorescence background, strong penetration ability under near‐infrared (NIR) radiation, resistance to photobleaching, and low toxicity. Although UCNPs hold great promise in nanotechnology and nanomedicine, their applications in ECL fields still remain unexplored. Herein, a label‐free, ultra‐sensitive and selective electrochemiluminescence (ECL) assay is developed for detection of cyclin A₂ by using highly efficient ECL graphene‐upconversion hybrid. Being an important member of the cyclin family, cyclin A₂ is involved in the initiation of DNA replication, transcription and cell cycle reg­ulation through the association of cyclin‐dependent kinases (CDK). Cyclin A₂ is a prognostic indicator in early‐stage cancers and a target for treatment of different types of cancers. However, the expression level of cyclin A₂ is quite low, direct detection of cyclin A₂ in crude cancer cell extracts is challenging and important for both clinical diagnosis of cancer in the early stage and the treatment. By chemically grafting cyclin A₂ detection specific probe, a PEGlyted hexapeptide, to graphene‐upconversion hybrid, the constructed ECL biosensor displays a superior performance for cyclin A₂, which can not only detect cyclin A₂ directly in cancer cell extracts, but also discriminate between normal cells and cancer cells. More importantly, the ECL biosensor has different responses between clinical used anticancer drug‐treated and non‐treated cancer cells, which demonstrates that the sensor can be potentially used for drug screening, and for evaluation of therapeutic treatments in early‐stage cancers.

Multifunctional lanthanide‐doped porous nanoparticles are prepared via a facile one‐step solvothermal route by employing aptamers as the biotemplate. The nanoparticles feature excellent aqueous dispersibility and biospecific properties and could work as effective nanoprobes for targeted imaging and drug delivery. With aptamer being in principle available for any kind of target, this synthetic strategy may open the door to a new generation of nanoprobes for bioapplications such as time‐resolved biodetection, multimode bioimaging/biolabeling, and targeted cancer therapy.