A near-infrared fluorescent probe with viscosity sensitivity in lysosome for cancer visualization.

A viscosity-sensitive, lysosome-targeted near-infrared fluorescent probe (PYATT) was reported in this paper. The fluorescent spectra of PYATT are strongly dependent on viscosity, resulting in a Stokes shift of about 190 nm. Given its photostability, low cytotoxicity, and high fluorescence quantum yield, PYATT is expected to be used in cell imaging. Due to the higher viscosity of tumor cells than normal cells, the fluorescence intensity of PYATT in tumor cells is higher than normal cells, which can realize the visualization of tumors. The near-infrared probe (PYATT) is viscosity-dependent in lysosomes, which is valuable in early diagnosis and treatment of tumor.

Rational design of water-soluble mitochondrial-targeting near-infrared fluorescent probes with large Stokes shift for distinguishing cancerous cells and bioimaging.

In the paper, two new near-infrared fluorescent probes (TTHPs) with D-π-A structure were successfully synthesized. TTHPs exhibited polarity and viscosity sensitivity and mitochondrial targeting under physiological conditions. The emission spectra of TTHPs showed strong polarity/viscosity dependence with more than a large Stokes shift of 200 nm. Based on their unique merits, TTHPs were used to distinguish cancerous and normal cells, which could be new tools for cancer diagnosis. Moreover, TTHPs were the first to achieve biological imaging of Caenorhabditis elegans, which could be labeling probes to apply in multicellular organisms.

Carrier-Free Delivery of Ultrasmall π-Conjugated Oligomer Nanoparticles with Photothermal Conversion over 80% for Cancer Theranostics.

High-performance photothermal theranostics is urgently desired for cancer therapy because of their good controllability and noninvasive features. The relatively low photothermal conversion efficiency is still at the drawbacks because of the absence of efficient extraneous carriers. Herein, a carrier-free nanomedicine is developed to in vivo self-deliver organic photothermal agents for efficient cancer phototheranostics. By a facile self-assembly strategy, the near-infrared (NIR)-absorbing conjugated oligomer IDIC-4F is fabricated into a carrier-free nanoparticle (DCF-P), showing ultrasmall size of nearly 4.0 nm with a nearly 100% of drug loading capacity. Notably, DCF-P achieves a superhigh photothermal conversion efficiency of 80.5% that is far greater than that of IDIC-4F-loaded nanomicelle DCF-M (57.3%). With the guidance of NIR fluorescence and photoacoustic dual-imaging, it is verified that DCF-P could well achieve tumor-preferential accumulation and retention at 4 h postinjection, and meanwhile shows highly efficient in vivo tumor elimination with good biosafety. This study thus contributes a novel concept for designing ultrasmall nanoparticle characteristics of preferential accumulation in tumors, and also provides a strategy for creating high-performance carrier-free nanomedicine via highly ordered molecular stacking.

Indocyanine green loaded pH-responsive bortezomib supramolecular hydrogel for synergistic chemo-photothermal/photodynamic colorectal cancer therapy.

Colorectal cancer is with high incidence worlwide.. Because of the heterogeneity of the tumor, combination therapy is probably of great significance to improve the prognosis of colorectal cancer patients. Herein, the pH-responsive supramolecular hydrogels mPEG-luteolin-BTZ@ICG based on bortezomib (BTZ) and indocyanine green (ICG) were prepared, and the colorectal cancer was treated with mPEG-luteolin-BTZ@ICG through the combination of photothermal/photodynamic and chemotherapy. BTZ performed drug therapy, meanwhile ICG wrapped in supramolecular hydrogels possessed higher light stability than free ICG to perform photothermal/photodynamic therapy. In vitro and in vivo assays showed excellent inhibition of tumor cells due to the combined effect of BTZ and ICG. The mPEG-luteolin-BTZ@ICG combined with laser therapy possessed exceptional biological safety and provided new candidates for advanced colon cancer therapy and important references for other tumor therapies.

Molecular engineering of diketopyrrolopyrrole-conjugated polymer nanoparticles by chalcogenide variation for photoacoustic imaging guided photothermal therapy.

Photothermal therapy is promising for augmenting cancer therapeutic outcomes in cancer treatment. Diketopyrrolopyrrole (DPP)-conjugated polymer nanoparticles are in focus due to their dual photoacoustic imaging and photothermal therapy functions. Herein, the design and synthesis of three near-infrared absorbing conjugated polymers, named DPP-SO, DPP-SS and DPP-SSe, with heteroatom substitution of the thiophene moiety were developed for a photoacoustic imaging guided photothermal therapy. It was demonstrated that systematically changing only the heteroatom from O to S or Se could apparently adjust the absorption spectrum and energy gap of DPP-conjugated polymers to obtain the most suitable photothermal transduction agents (PTAs) for use in biomedicine. The characterization of photophysical properties proved that the photothermal conversion efficiency and absorption coefficient of DPP-SO nanoparticles under 808 nm irradiation was up to 79.3% and 66.51 L g-1 cm-1, respectively, which were much higher than those of DPP-SS and DPP-SSe nanoparticles. Remarkably, the IC50 value of DPP-SO for killing A549 cells was half that of DPP-SS and DPP-SSe nanoparticles. Further in vivo works demonstrated efficient photothermal therapeutic effects of DPP-SO nanoparticles with the guidance of photoacoustic imaging. Thus, this is an efficient method to regulate the photothermal performance of DPP-conjugated polymers by changing the heteroatom in the molecular skeleton.

Regioisomer-manipulating thio-perylenediimide nanoagents for photothermal/photodynamic theranostics.

Thionated perylenediimides (PDIs) can potentially generate thermal and reactive oxygen species and thus can be used as theranostic agents for photothermal/photodynamic therapy. Herein, thionated cis-/trans-isomer PDI-CS and PDI-TS were designed and prepared to investigate thionation engineering on therapeutic performance. The results revealed that the photodynamic performance is less associated with the positon of sulfur atoms. By contrast, trans-isomer PDI-TS showed a photothermal conversion efficiency of up to 58.4%, which was 40% higher than that of PDI-CS (∼41.6%). An in vitro half-maximal inhibitory concentration of ∼7.78 µg mL-1 was achieved for PDI-TS, which was 1.7-fold smaller than that of PDI-CS, strongly reasserting the regioisomer-modulated phototheranostic performance. Notably, the strong π-π and CS interactions in PDI-TS nanoagents are essential factors attributed to their excellent photothermal performance, indicating that the optimization of non-bonding interactions is an ingenious way to improve phototheranostic performance. This work provides a facile means of creating thio-perylenediimides that possess excellent antitumor properties and a novel proof of concept to improve therapeutic performance through the optimization of non-bonding interactions.

Bis-diketopyrrolopyrrole conjugated polymer nanoparticles as photothermic nanoagonist for specific and synergistic glioblastoma therapy.

Development of high-performance photoactive agents with tumor-specific capability for effective nanotherapeutics has received much attention in the past decades. Herein, we report a nanotherapeutic based on bis-diketopyrrolopyrrole (BDPP) conjugated polymer nanoparticles (PBDPP NPs) with remarkable near-infrared (NIR) absorption at 808 nm and high photothermal energy conversion efficiency up to 60%. In particular, precise glioblastoma-specific capability and killing ability for glioblastoma cells were effectively achieved in vitro by treating with only PBDPP NPs to induce cell apoptosis or by interaction with PBDPP NPs under NIR laser irradiation to trigger cell necrosis. Impressively, a half-maximal inhibitory concentration as low as of ∼0.15 µg mL-1 was achieved, and the magnitude is 5 to 4.4 × 104-fold lower than those of reported agents. In vivo experiment with mice further shows that the PBDPP NPs show good efficacy of photothermal therapy and complete tumor elimination using a record-low dosage of 0.35 mg mL-1 under 808 nm irradiation of low power (0.5 W cm-2). This study thus demonstrates a promising strategy of low-dose, high-efficacy polymer-based nanoagonist for specific phototherapy of glioblastoma.

Chalcogen-substitution modulated supramolecular chirality and gas sensing properties in perylenediimides.

We present the modulation of van der Waals interactions to further adjust supramolecular chirality by incorporation of S and Se into the bay region. These chalcogen atom-mediated supramolecular interactions were transferred to nanostructures and affected the gas responses of devices. This study will facilitate the development of smart materials with modulated handedness in materials science.

On-off-on fluorescent carbon dots from waste tea: Their properties, antioxidant and selective detection of CrO42-, Fe3+, ascorbic acid and L-cysteine in real samples.

In this work, we reported an economical plant-based hydrothermal method for one-pot green synthesis of water-soluble carbon dots (Tea-CDs) by using waste tea extract as a carbon source. The synthesized Tea-CDs were characterized by UV-visible, fluorescence, FT-IR, TEM, XPS and XRD. The Tea-CDs were found to remove hydroxyl and superoxide anion radical in vitro. In addition, the Tea-CDs exhibited bright blue fluorescence under UV-light (λex = 365 nm), and the fluorescence could be effectively quenched by CrO42- and Fe3+ ions. Meanwhile, the fluorescence of Tea-CDs-CrO42- and Tea-CDs-Fe3+ systems could be again easily recovered by ascorbic acid (AA) and L-cysteine (L-Cys). As an on-off-on fluorescent nano-sensor of the Tea-CDs, the sensitive detection of CrO42-, Fe3+, AA and L-Cys were all performed, showing that the good linear relationships between fluorescence intensity of Tea-CDs and concentration of all testing samples. Finally, the sensors successfully detected CrO42-, Fe3+, AA and L-Cys in commercially available real samples with satisfactory recovery ranges. The prepared sensors offer distinct advantages including low cost, simple handling, good sensitivity and high selectivity.

AIEgen Nanoparticles of Arylamino Fumaronitrile Derivative with High Near-Infrared Emission for Two-Photon Imaging and in Vivo Cell Tracking.

Developing of two-photon materials for live-cell imaging and in vivo analysis in-depth have received great attention, and it is urgent so that such microscopy techniques could be promoted and advanced using the powerful probes. Herein, a new arylamino fumaronitrile derivative NPAPF was synthesized and transferred as aggregation-induced emission luminogen (AIEgen) fluorescent nanoparticles (AF-NPs) via assembly technique. This AF-NP exhibited a two-photon absorption cross-section at 2.6 × 106 GM with 19.5% of fluorescence quantum yield. Moreover, utilizing the great potential of AF-NPs, two-photon imaging of live cells with good cytocompatibility is realized upon two-photon microscopy. By in vivo long-term tracing studies of mesenchymal stem cells, we demonstrated the tremendous advantage of AF-NPs tracer in monitoring the stem cells transplant. Therefore, our unique AF-NPs provided an efficient two-photon-absorbing probe for investigating biological mechanism and behavior, and opened a new avenue for spatiotemporal visualization of transplanted stem cells.

Characterisation of the mucilage polysaccharides from Dioscorea opposita Thunb. with enzymatic hydrolysis.

The mucilage polysaccharides from Dioscorea opposita (DOMP) were extracted and treated with a single/dual enzymatic hydrolysis. The characterisation and viscosity were subsequently investigated in this study. DOMP obtained 62.52% mannose and 23.45% glucose. After single protease and trichloroacetic acid (TCA) treatments, the mannose content was significantly reduced to 3.96%, and glucose increased from 23.45% to 45.10%. Dual enzymatic hydrolysis also decreased the mannose and glucose contents to approximately 18%-35% and 7%-19%, respectively. The results suggest that enzymatic degradation could effectively remove the protein from DOMP accompanied by certain polysaccharides, especially mannose. The molecular weight, surface morphology, viscosity and particle sizes were measured. Enzymatic hydrolysis reduced molecular weight, decreased the viscosity, and increased the particle sizes, which indicates that the characterisations of DOMP samples were altered as structures changed. This study was a basic investigation into characterisation of DOMP to contribute to the processing of food by-products.

Functionalization of silver nanoparticles with mPEGylated luteolin for selective visual detection of Hg2+ in water sample.

A novel colorimetric sensor based on mPEGylated luteolin-functionalized silver nanoparticles (mPEGylated luteolin-AgNPs) in an aqueous solution was prepared. The mPEGylated luteolin-AgNP solution was utilized to detect Hg2+ with high sensitivity and selectivity in the presence of other metal cations including Na+, K+, Mg2+, Zn2+, Ni2+, Mn2+, Ba2+, Pb2+, Sr2+, Ca2+, Cd2+, Al3+ and Cu2+. The solution could be induced to aggregate, and a color change from yellow-brown to colorless was observed in the presence of Hg2+. Meanwhile, the sensor was successfully used to detect Hg2+ in tap water with satisfactory recovery ranges using the standard addition method.

Facile synthesis of mPEG-luteolin-capped silver nanoparticles with antimicrobial activity and cytotoxicity to neuroblastoma SK-N-SH cells.

We firstly report a facile route for the green synthesis of mPEG-luteolin-capped silver nanoparticles (mPEG-luteolin-AgNPs) using mPEG-luteolin as both the reducer and stabilizer. The reaction was carried out in a stirred aqueous solution at 50°C without additional poisonous reagents. The prepared mPEG-luteolin-AgNPs was characterized by scanning electron microscope (SEM), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), zeta potential and UV-vis (UV-vis) spectrum, respectively. The proportions of mPEG-luteolin capped silver nanoparticles is about 89.9%, and the content of silver is 6.65%. The mPEG-luteolin-AgNPs was evaluated the antimicrobial effects on Staphlococcus aureus, Extended spectrum ß-Lactamases Staphlococcus aureus, Escherichia Coli and Extended spectrum ß-Lactamases Escherichia Coli using drilling hole method. The results showed that both gram-positive and gram-negative bacteria were killed by the mPEG-luteolin-AgNPs at low concentration. Meanwhile, the cell viability assay demonstrated that mPEG-luteolin-AgNPs had toxic effects on human neuroblastoma SK-N-SH cells.

Preparation and Characterization of Copolymer Micelles for the Solubilization and In Vitro Release of Luteolin and Luteoloside.

Luteolin (LUT) and luteoloside (LUS) belong to flavonoids with high anticancer potential and were loaded into biodegradable diblock copolymer micelles of methoxy polyethylene glycol-polycaprolactone (mPEG5K-PCL10K), methoxy polyethylene glycol-polylactide-co-glycolide (mPEG5K-PLGA10K), and methoxy polyethylene glycol-polylactide (mPEG5K-PDLLA10K) by a self-assembly method, creating water-soluble LUT and LUS copolymer micelles, respectively. The solubilization formulations of the copolymer micelles were optimized with response surface methodology (RSM). The obtained drug micelles are torispherical under transmission electron microscope (TEM) with an average diameter of about 70 nm. The mPEG5K-PLGA10K exhibited higher loading capacity for LUS which was 4.33%, and LUT- (or LUS)-loaded mPEG5K-PCL10K exhibited a better stability and encapsulation efficiency which was 65.1 and 55.8%, respectively. The in vitro drug release study showed above 47% of LUT was released from micelles at pH 7.4 PBS; however, no more than 35% of LUT was released at pH 6.4 PBS within 24 h. Meanwhile, no more than 30% of LUS was released from micelles whether at pH 6.4 or 7.4 PBS solution within 24 h.

1-(5-Bromo-2-hydr-oxy-4-methoxy-phen-yl)ethanone.

In the title compound, C(9)H(9)BrO(3), the dihedral angle between the ethanone group and the aromatic ring is 3.6 (2)°. The mol-ecular conformation is consolidated by an intra-molecular O-H⋯O hydrogen bond. The crystal structure is stabilized by π-π inter-actions between the benzene rings [centroid-centroid distance = 3.588 (2) Å].

N-(4-Bromo-2-methyl-phen-yl)pivalamide.

The conformation of the N-H bond in the title compound, C(12)H(16)BrNO, is syn to the ortho-methyl substituent. There are two unique molecules in the asymmetric unit. In the crystal structure, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules, forming infinite chains down [010].

2-Bromo-1-(4-hydroxy-phen-yl)ethanone.

There are two mol-ecules in the asymmetric unit of the title compound, C(8)H(7)BrO(2). In the crystal, they form independent chains propagating in [010] linked by O-H⋯O hydrogen bonds.

5,3'-Dihydr-oxy-7,4'-dimethoxy-flavanone from Artemisia sphaerocephala Kraschen.

The title compound, C(17)H(16)O(6), was isolated from the Chinese Tibetan medicinal plant Artemisia sphaerocephala Kraschen. The mol-ecular conformation is consolidated by two intra-molecular O-H⋯O hydrogen bonds. A further inter-molecular O-H⋯O hydrogen bond leads to chains along [010] in the crystal structure.