Bipolar hemicyanine cationic probe for simultaneous sensing of ATP and GTP.

Adenosine 5'-triphosphate (ATP) and guanosine 5'-triphosphate (GTP) are the most essential energy source in enormous biological processes. Various probes for ATP or GTP sensing, have been widely established, but the probe that could simultaneously monitor ATP and GTP is still rarely reported. Herein, we report a bipolar hemicyanine cationic probe for simultaneous sensing of ATP and GTP via a one-step monitoring process. This probe exhibited strong affinity to ATP and GTP through intramolecular electrostatic and π-π stacking interactions, which the binding constant on each step were determined as 6.15 × 107 M-1 and 1.57 × 106 M-1 for ATP, 3.19 × 107 M-1 and 3.81 × 106 M-1 for GTP. The sensitivity and specificity of this probe toward ATP or GTP over other twelve biological analogues (adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP), guanosine 5'-diphosphate (GDP), guanosine 5'-monophosphate (GMP), Etc.) have also been successfully demonstrated. Furthermore, due to the rapid response rate (within 10 s), we also proved that this probe could be employed as a monitor tool during the ATP or GTP-related enzymatic reaction process.

A biophotonic device based on a conjugated polymer and a macrophage-laden hydrogel for triggering immunotherapy.

A biophotonic device is fabricated by a 3D printing technique for tumor immunotherapy utilizing a flexible organic light-emitting diode (OLED) with deep blue emission and a gelatin-alginate hydrogel that contains a poly(phenylene vinylene) (PPV) derivative and live immune cells of macrophages (M0-RAW264.7). PPV is excited by the OLED to generate reactive oxygen species (ROS), enabling the macrophages to polarize to the M1 phenotype and secrete cytotoxic cytokines to induce the apoptosis of tumor cells. This strategy provides a new method for fabricating cell-involved biophotonic devices for immunotherapy.

Selective Fluorescence Imaging of Cancer Cells Based on ROS-Triggered Intracellular Cross-Linking of Artificial Enzyme.

Inside living cells, regulation of catalytic activity of artificial enzymes remains challenging due to issues such as biocompatibility, efficiency, and stability of the catalyst, by which the practical applications of artificial enzymes have been severely hindered. Here, an artificial enzyme, PTT-SGH, with responsiveness to reactive oxygen species (ROS), was obtained by introducing a catalytic histidine residue to pentaerythritol tetra(3-mercaptopropionate) (PTT). The artificial enzyme formed large aggregates in cells via the intracellular ROS-mediated oxidation of thiol groups. The process was significantly facilitated in tumor cells because of the higher ROS concentration in the tumor microenvironment. The catalytic activity of this artificial enzyme was intensively enhanced through deprotonation of cross-linked PTT-SGH, which showed typical esterase activities. Selective fluorescence imaging of tumor cells was achieved using the artificial enzyme to trigger the cleavage of the ester bond of the caged fluorophore inside living cells.

Near-Infrared-Light Remote-Controlled Activation of Cancer Immunotherapy Using Photothermal Conjugated Polymer Nanoparticles.

Remote control of the therapeutic process is an ideal strategy for maximizing efficacy and avoiding side effects, especially for cancer immunotherapy. Herein, a conjugated polymer nanoparticles (CPNs)-mediated optogenetic system for in situ activation of immunotherapy under near-infrared laser irradiation is reported. This system is composed of photothermal CPNs and interferon-gamma (IFN-γ) plasmid driven by heat shock promoter HSP70. The photothermally responsive CPNs serve as a photo-heat nanotransducer to trigger the gene transcription of IFN-γ cytokine. The secreted IFN-γ from cancer cells can sufficiently elicit surrounding tumor-associated macrophages activation through IFN-γ-JAK-STAT1 transcription-factor signaling pathway and finally induce cancer cell killing by immunotherapy. Therefore, this synergetic optogenetic system provides a promising approach to remotely control the process of cancer immunotherapy.

Polymer nanoparticles regulate macrophage repolarization for antitumor treatment.

We demonstrate an intrinsic antitumor effect of polymer nanoparticles (P-NPs), which could re-program tumor-associated macrophages to pro-inflammatory phenotype. The intrinsic effect of P-NPs on macrophage repolarization and its combination with other therapies provide new ideas for drug delivery, macrophage regulation and immunotherapy in cancer treatment.