Tannic acid and carboxymethyl chitosan-based multi-functional double-layered hydrogel with pH-stimulated response behavior for smart real-time infection monitoring and wound treatment.

The dramatic increase of drug-resistant pathogenic bacteria has seriously effect on human health, appealing the needs of developing theranostic platforms with stimuli-responsive materials to realize the accurate bacterial diagnostics and therapeutics. Herein, a tannic acid and carboxymethyl chitosan-based multifunctional ZIF-90@i-PPOPs-phenol red double-layered hydrogel with stimuli-responsiveness and antibacterial activity was fabricated. The inner layer hydrogel (ZIF-90@i-PPOPs-based TFC hydrogels) was fabricated based on ZIF-90@i-PPOPs, integrate tannic acid and carboxymethyl chitosan linked by formylphenylboronic acid (FPBA), which exhibited outstanding injectable, biodegradability and antibacterial activity. The outer layer hydrogel (PR@PAM hydrogels) were constructed from polyacrylamide (PAM) and pH indicator phenol red, owning porous structure and excellent tissue adhesion. Due to the weakly acidic microenvironment within wound, the inner-layer hydrogel was stimulus-responsively decomposed, resulting in the accurate delivery of the positively charged ZIF-90@i-PPOPs to the lesion site to capture and kill bacteria by enhanced Zn2+ and ROS release. Meantime, the outer-layer hydrogel could real-timely monitor the pH changes to evaluate the wound recovery status. These double-layered hydrogels possessed precisely pH monitoring capacity, excellent antibacterial ability and negligible side effect to normal tissue in vivo, implying the high potential of the suggested hydrogels as theranostic platform for antibacterial treatment.

An integrated liquid crystal sensing device assisted by the surfactant-embedded smart hydrogel.

The abnormal levels of trypsin in biological fluids can cause some acute illnesses, such as acute pancreatitis, cystic fibrosis and malnutrition. In this paper, we report the development of an integrated liquid crystal (LC) sensing device for simple, rapid and sensitive detection of trypsin assisted by the surfactant-embedded smart hydrogel. The gelatin hydrogel mixed with CTAB is added into the side channel of the LC sensing device. In the presence of trypsin, the gelatin hydrogel is decomposed, which triggers instant release of CTAB into the aqueous solution. The CTAB molecules are then captured by the LCs and form CTAB monolayers at the aqueous/LC interface, which leads to change of the LC images from the bright to the dark appearance under the crossed polarizers. The integrated LC sensing device has a remarkable detection limit of 3.4 × 10-5 mg/mL. It is successfully employed to single-step detection of trypsin in human serum within 30 min. The integrated LC sensing device with use of the surfactant-embedded hydrogel takes advantages of single-step detection, high portability, remarkable sensitivity and fast response time, which provides a new perspective to facilitate development of user-friendly LC-based sensors.

Neutrophils in cancer-unresolved questions.

There is growing recognition that neutrophils play an important role in cancer initiation, progression and metastasis. Although they are typically characterized as short-lived effector cells, neutrophils have been shown to acquire immunosuppressive and pro-tumorigenic functions that promote tumor progression and escape. As such, inhibition of their function or depletion of neutrophils are being explored as potential cancer therapies. However, growing evidence of neutrophil diversification in cancer and their potential anti-tumor roles raise many unresolved questions. Here, we review recent advances that address the definition, origin and function of neutrophils in cancer, and elaborate on obstacles that make the study of neutrophils challenging. We envision that this review will provide the groundwork for focused design of therapeutics that will specifically target "tumorreprogrammed" neutrophils while sparing normal neutrophils to improve patient outcomes.

Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8+ T cell immunity.

Recent studies in both mice and humans have suggested that gut microbiota could modulate tumor responsiveness to chemo- or immunotherapies. However, the underlying mechanism is not clear yet. Here, we found that gut microbial metabolites, especially butyrate, could promote the efficacy of oxaliplatin by modulating CD8+ T cell function in the tumor microenvironment. Butyrate treatment directly boosted the antitumor cytotoxic CD8+ T cell responses both in vitro and in vivo in an ID2-dependent manner by promoting the IL-12 signaling pathway. In humans, the oxaliplatin responder cancer patients exhibited a higher amount of serum butyrate than did non-responders, which could also increase ID2 expression and function of human CD8+ T cells. Together, our findings suggest that the gut microbial metabolite butyrate could promote antitumor therapeutic efficacy through the ID2-dependent regulation of CD8+ T cell immunity, indicating that gut microbial metabolites could be effective as a part of cancer therapy.

Low-background electrochemical biosensor for one-step detection of base excision repair enzyme.

We develop a low-background electrochemical biosensor for one-step detection of uracil DNA glycosylase (UDG) based on the host-guest interaction and iron-embedded nitrogen-rich carbon nanotube (Fe-N-C) that mimics enzyme-mediated electrocatalysis to achieve signal amplification. In this work, Fe-N-C is initially immobilized on a glassy carbon electrode, followed by the immobilization of ß-cyclodextrin (ß-CD). We construct the signal probes by assembling the methylene blue (MB)-labeled hairpin DNAs onto the surface of Au nanoparticles (AuNPs) to form the MB-hairpin/AuNP probes. Due to the steric effect of AuNPs and the stem-loop structure of hairpin DNA, MB is prevented from entering the cavity of ß-CD on the electrode. In contrast, UDG enables the removal of uracil from the U•A pairs in the stem of hairpin DNA probe to generate apurinic/apyrimidinic (AP) sites, leading to the assembly of MB-hairpin/AuNP probes on the electrode based on host-guest reaction between ß-CD and MB. Meanwhile, L-cysteine (RSH) is oxidized by O2 to disulfide L-cystine (RSSR) and H2O2. In the presence of H2O2, Fe-N-C catalyzes the oxidation of MB to generate an amplified electrochemical signal. Notably, the Fe-N-C-catalyzed oxidation of MB is mediated by the oxidation of RSH by O2 instead of external H2O2, greatly simplifying the experimental procedures and improving the electrochemical signal. Due to the introduction of host-guest recognition, this electrochemical biosensor displays a low-background signal and high signal-to-noise ratio, enabling the one-step sensitive measurement of UDG with a detection limit of 7.4 × 10-5 U mL-1. Moreover, this biosensor can measure UDG in crude cell extracts and screen the inhibitors, providing a new platform for biomedical research.

Near-infrared and metal-free tetra(butylamino)phthalocyanine nanoparticles for dual modal cancer phototherapy.

Synergistic phototherapy combining photodynamic therapy (PDT) and photothermal therapy (PTT) based on near-infrared (NIR) dyes using a single light source offers the opportunity to treat diseases at deep locations. In this study, we reported human serum albumin (HSA)-involving tetra(butylamino)phthalocyanine (Pc)-based nanomaterials of HSA-α-Pc and HSA-ß-Pc as highly efficient dual-phototherapy agents, namely 1(4),8(11),15(18),22(25)-tetra(butylamino)phthalocyanine (α-Pc) and 2(3),9(10),16(17),23(24)-tetra(butylamino)phthalocyanine (ß-Pc). Both HSA-α-Pc and HSA-ß-Pc showed excellent photothermal effects under a single NIR (808 nm) laser irradiation due to the S 1 fluorescence emission quenching of Pcs. Compared to HSA-ß-Pc, HSA-α-Pc exhibited better singlet oxygen generation ability and its highly efficient PDT/PTT dual-phototherapy was also well evidenced via in vitro and vivo experiments under a single 808 nm laser irradiation. Overall, this approach would be viable for the fabrication of more new Pc-based metal-free nano agents for PDT/PTT synergistic phototherapy upon a single NIR light source.

Surface Decorated Porphyrinic Nanoscale Metal-Organic Framework for Photodynamic Therapy.

Nanocrystallization of organic molecular photosensitizers (PSs) by means of NMOF platforms has been demonstrated to be a promising approach to build up highly efficient PDT therapeutics. We report herein a new UiO-66 type of NMOF-based PS (UiO-66-TPP-SH), which is generated from UiO-66 NMOF and S-ethylthiol ester monosubstituted metal free porphyrin (TPP-SH) via a facile postsynthetic approach under mild conditions. The obtained NMOF (size less than 150 nm) with surface-decorated porphyrinic PS can not only retain MOF crystallinity, structural feature, and size, but also exhibit highly efficient singlet oxygen generation. Compared to the interior-located porphyrinic NMOF, UiO-66-TPP-SH shows significantly higher photodynamic activity and more efficient PDT tumor treatment.

Direct detection of circulating free DNA extracted from serum samples of breast cancer using locked nucleic acid molecular beacon.

As an emerging noninvasive blood biomarker, circulating free DNA (cfDNA) can be utilized to assess diagnosis, progression and evaluate prognosis of cancer. However, cfDNAs are not "naked", they can be part of complexes, or are bound to the surface of the cells via proteins, which make the detection more challenging. Here, a simple method for the detection of Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) DNA exacted from serum of breast cancer (BC) has been developed using a novel locked nucleic acid molecular beacon (LNA-MB). In order to enhance the stability and detection efficiency of the probe in biofluids, we design a shared-stem molecular beacon containing a 27-mer loop and a 4-mer stem with DNA/LNA alternating bases. The fluorescence is released in the presence of target. The detection procedure is simple and can be completed within 1h. This method shows a sensitive response to UHRF1 DNA with a dynamic range of 3 orders of magnitude. The limit of detection is 11nM (S/N=3) with excellent selectivity. It can discriminate UHRF1 DNA from three-base mismatched DNA with a high specificity. More importantly, this method can distinguish the expression of serum UHRF1 DNA among 5 breast cancer patients and 5 healthy controls. The mentioned superiority may suggest that this assay can be served as a promising noninvasive detection tool for early BC diagnosis and monitoring.

A peptide nucleic acid-functionalized carbon nitride nanosheet as a probe for in situ monitoring of intracellular microRNA.

A novel probe for recognition of both cancer cells and intracellular microRNA (miRNA) is designed by functionalizing a carbon nitride nanosheet (f-CNNS) with a Cy5-labeled peptide nucleic acid (Cy5-PNA) and folate. The interaction between Cy5-PNA and CNNS quenches the fluorescence of Cy5, and the presence of folate endows the probe with good specificity to folate acceptor overexpressed cells. The probe can be specifically taken up by cancer cells with an incubation step. Upon the recognition of the PNA to complementary miRNA, the hybridization product is released from the CNNS surface, which leads to the fluorescence recovery and provides a specific method for sensing of miRNA. Thus, this probe can be used for cell-specific intracellular miRNA sensing with a confocal microscope. Using miRNA-18a as a target model, the dynamic changes of its expression level inside living cells can be monitored with the proposed method. This method possesses promising applications in the study of miRNA related bioprocesses and biomedicine.

Folate receptor-targeted and cathepsin B-activatable nanoprobe for in situ therapeutic monitoring of photosensitive cell death.

The integration of diagnostic and therapeutic functions in a single system holds great promise to enhance the theranostic efficacy and prevent the under- or overtreatment. Herein, a folate receptor-targeted and cathepsin B-activatable nanoprobe is designed for background-free cancer imaging and selective therapy. The nanoprobe is prepared by noncovalently assembling phospholipid-poly(ethylene oxide) modified folate and photosensitizer-labeled peptide on the surface of graphene oxide. After selective uptake of the nanoprobe into lysosome of cancer cells via folate receptor-mediated endocytosis, the peptide can be cleaved to release the photosensitizer in the presence of cancer-associated cathepsin B, which leads to 18-fold fluorescence enhancement for cancer discrimination and specific detection of intracellular cathepsin B. Under irradiation, the released photosensitizer induces the formation of cytotoxic singlet oxygen for triggering photosensitive lysosomal cell death. After lysosomal destruction, the lighted photosensitizer diffuses from lysosome into cytoplasm, which provides a visible method for in situ monitoring of therapeutic efficacy. The nanoprobe exhibits negligible dark toxicity and high phototoxicity with the cell mortality rate of 0.06% and 72.1%, respectively, and the latter is specific to folate receptor-positive cancer cells. Therefore, this work provides a simple but powerful protocol with great potential in precise cancer imaging, therapy, and therapeutic monitoring.

Simultaneous sensing of intracellular microRNAs with a multi-functionalized carbon nitride nanosheet probe.

A multi-functionalized CNNS probe was designed by loading different dye-ssDNAs and folate on CNNSs, which was used for in situ fluorescence imaging and sensing of intracellular multiple microRNAs.

Bis{1-[(4-methyl-phen-yl)imino-meth-yl]-2-naphtho-lato-κN,O}nickel(II).

In the title complex, [Ni(C(18)H(14)NO)(2)], the Ni(II) ion lies on an inversion center and is coordinated in a slightly distorted square-planar environment. The 1-[(4-methyl-phen-yl)imino-meth-yl]-2-naphtho-late ligands are coordinated in a trans arrangement with respect to the N and O atoms. In the symmetry-unique ligand, the dihedral angle between the naphthalene ring system and the benzene ring of the methyl-phenyl group is 49.03 (7)°.