Core-Shell-Shell Multifunctional Nanoplatform for Intracellular Tumor-Related mRNAs Imaging and Near-Infrared Light Triggered Photodynamic-Photothermal Synergistic Therapy.

A multifunctional nanoplatform, which generally integrates biosensing, imaging diagnosis, and therapeutic functions into a single nanoconstruct, has great important significance for biomedicine and nanoscience. Here, we developed a core-shell-shell multifunctional polydopamine (PDA) modified upconversion nanoplatform for intracellular tumor-related mRNAs detection and near-infrared (NIR) light triggered photodynamic and photothermal synergistic therapy (PDT-PTT). The nanoplatform was constructed by loading a silica shell on the hydrophobic upconversion nanoparticles (UCNPs) with hydrophilic photosensitizer methylene blue (MB) entrapped in it, and then modifying PDA shells through an in situ self-polymerization process, thus yielding a core-shell-shell nanoconstruct UCNP@SiO2-MB@PDA. By taking advantages of preferential binding properties of PDA for single-stranded DNA over double-stranded DNA and the excellent quenching property of PDA, a UCNP@SiO2-MB@PDA-hairpin DNA (hpDNA) nanoprobe was developed through adsorption of fluorescently labeled hpDNA on PDA shells for sensing intracellular tumor-related mRNAs and discriminating cancer cells from normal cells. In addition, the fluorescence resonance energy transfer from the upconversion fluorescence (UCF) emission at 655 nm of the UCNPs to the photosensitizer MB molecules could be employed for PDT. Moreover, due to the strong NIR absorption and high photothermal conversion efficiency of PDA, the UCF emission at 800 nm of the UCNPs could be used for PTT. We demonstrated that the UCNP@SiO2-MB@PDA irradiated with NIR light had considerable PDT-PTT effect. These results revealed that the developed multifunctional nanoplatform provided promising applications in future oncotherapy by integrating cancer diagnosis and synergistic therapy.

High familiar faces have both eye recognition and holistic processing advantages.

People recognize familiar faces better than unfamiliar faces. However, it remains unknown whether familiarity affects part-based and/or holistic processing. Wang et al., Frontiers in Psychology, 6, 559 (2015), Vision Research, 157, 89-96 (2019) found both enhanced part-based and holistic processing in eye relative to mouth regions (i.e., in a region-selective manner) for own-race and own-species faces, i.e., faces with more experience. Here, we examined the role of face familiarity in eyes (part-based, region-selective) and holistic processing. Face familiarity was tested at three levels: high-familiar (faces of students from the same department and the same class who attended almost all courses together), low-familiar (faces of students from the same department but different classes who attended some courses together), and unfamiliar (faces of schoolmates from different departments who seldom attended the same courses). Using the old/new task in Experiment 1, we found that participants recognized eyes of high-familiar faces better than low-familiar and unfamiliar ones, while similar performance was observed for mouths, indicating a region-selective, eyes familiarity effect. Using the "Perceptual field" paradigm in Experiment 2, we observed a stronger inversion effect for high-familiar faces, a weaker inversion effect for low-familiar faces, but a non-significant inversion effect for unfamiliar faces, indicating that face familiarity plays a role in holistic processing. Taken together, our results suggest that familiarity, like other experience-based variables (e.g., race and species), can improve both eye processing and holistic processing.

A new type of bilayer dural substitute candidate made up of modified chitin and bacterial cellulose.

In the field of neurosurgery, timely and effective repair of dura mater plays an important role in stabilizing the physiological functions of the human body. Therefore, the aim of this study is to develop a new type of bilayer membrane as a dural substitute candidate. It consists of a dense layer that prevents cerebrospinal fluid leakage and a porous layer that promotes tissue regeneration. The dense layer, a composite polysaccharid film, was composed of high molecular weight chitosan (CS) and bacterial cellulose (BC). The porous layer, a composite polysaccharid scaffold cross-linked by glutaraldehyde (GA) or citric acid (CA) respectively, was composed of O-carboxymethyl chitin (O-CMCH) and BC. The bilayer dural substitutes were characterized in terms of SEM, mechanical behavior, swelling rate, anti-leakage test, in vitro cytotoxicity, proliferation, and animal experiment. Results indicated that all prepared dural substitutes were tightly bound between layers without excessively large cavities. The porous layer showed appropriate pore size (90～200 µm) with high porous connectivity. The optimized bilayer dural substitutes showed suitable swelling rate and mechanical behavior. Furthermore, no leakage was observed during testing, no cytotoxicity effect on NIH/3T3 cells, and exhibited excellent cell proliferation promoting properties. Also, it was observed that it did not deform in the peritoneal environment of mice, and tissue inflammation was mild.

Cobalt Oxyhydroxide-prompted Synthesis of Fluorescent Polydopamine Nanoparticles for Glutathione Detection.

Glutathione (GSH) plays an important role in cells, which is an essential endogenous antioxidant. Here, we have developed a new detection platform to analyze GSH levels. In our system, fluorescent polydopamine (PDA) nanoparticles, as signal indicators, were obtained by oxidation through cobalt oxyhydroxide (CoOOH) nanosheets. When CoOOH was present, CoOOH could quickly oxidize dopamine to fluorescent PDA nanoparticles. However, once GSH existed, CoOOH nanosheets were decomposed into Co2+, and oxidation between CoOOH and dopamine was prevented with weaker fluorescence occurring. Thus, we could realize detection of the GSH concentration according to the decreased fluorescence value of the fluorescent polydopamine. This method provides a fast, simple, high sensitivity and desirable selectivity platform for GSH monitoring.

Sensitive fluorescence sensing of T4 polynucleotide kinase activity and inhibition based on DNA/polydopamine nanospheres platform.

5'-Polynucleotide kinase (PNK) is a crucial enzyme that catalyzes the phosphorylation of nucleic acid with 5'-OH termini and this phosphorylation reaction has been involved in many important cellular activities. The evaluation of PNK activity has received an increasing attention due to the significance of PNK. Here, the polydopamine nanospheres (PDANS) could adsorb single-stranded DNA (ssDNA) through π-π stacking or hydrogen bonding between nucleobases and aromatic groups of PDANS, while the interaction between double-stranded DNA (dsDNA) with PDANS was weakened due to the changed conformation. Hence, a novel DNA/PDANS platform was constructed for the sensitive and selective determination of T4 PNK activity based on the preferential binding properties of PDANS for ssDNA over dsDNA and the excellent fluorescence quenching property of PDANS. The dye-labeled dsDNA was phosphorylated by T4 PNK and then digested by λ exonuclease, yielding dye-labeled ssDNA, which would be adsorbed on the surface of the PDANS and the fluorescence was greatly quenched by PDANS. Because of the preferential binding properties of PDANS for ssDNA over dsDNA and the high quenching property of PDANS, the developed DNA/PDANS platform exhibited good analytical performance for T4 PNK sensing in complex biological matrix and applied to screening inhibitors. The proposed DNA/PDANS based platform is promising in developing high-throughput assays for drug screening and clinical diagnostics.

Folate-functionalized polymeric micelles for tumor targeted delivery of a potent multidrug-resistance modulator FG020326.

To overcome multidrug resistance (MDR) existing in tumor chemotherapy, polymeric micelles encoded with folic acid on the micelle surface were prepared with the encapsulation of a potent MDR modulator, FG020326. The micelles were fabricated from diblock copolymers of poly(ethylene glycol) (PEG) and biodegradable poly(epsilon-caprolactone) (PCL) with folate attached to the distal ends of PEG chains. The folate-conjugated copolymers, folate-PEG-PCL, were synthesized by multistep chemical reactions. First, allyl-terminated copolymer (allyl-PEG-PCL) was synthesized through a ring-opening polymerization of epsilon-caprolactone in bulk employing monoallyl-PEG as a macroinitiator. Second, the allyl terminal groups of copolymers were converted into primary amino groups by a radical addition reaction, followed by conjugation of the carboxylic group of folic acid. In vitro studies at 37 degrees C demonstrated that FG020326 release from micelles at pH 5.0 was faster than that at pH 7.4. Cytotoxicity studies with MTT assays indicated that folate-functionalized and FG020326-loaded micelles resensitized the cells approximately five times more than their folate-free counterparts (p < 0.01) in human KB(v200) cells treated with vincristine (VCR). The in vitro Rhodamine 123 efflux experiment using MDR KB(v200) cells revealed that when cells were pretreated with folate-attached and FG020326-loaded micelles, the P-glycoprotein (P-gp) drug efflux function was significantly inhibited.

FG020326-loaded nanoparticle with PEG and PDLLA improved pharmacodynamics of reversing multidrug resistance in vitro and in vivo.

AIM: FG020326, a novel imidazole derivative, is a potent multidrug-resistance (MDR) modulator in vitro and in vivo. However, FG020326 is insoluble. PEDLLA-FG020326 is a FG020326-loaded nanoparticle formed with diblock copolymers of poly (ethylene glycol)-block-poly (D,L-lactic acid) (PEG:PDLLA, PEDLLA) that can solubilize FG020326. This work was intended to evaluate the pharmacodynamics of PEDLLA-FG020326 on reversing MDR in vitro and in vivo. METHODS: Cytotoxicity was determined by tetrazolium assay. The intracellular accumulation and efflux of doxorubicin (Dox) were detected by fluorescence spectrophotometry. The function of P-glycoprotein was examined by Rhodamine 123 (Rh123) accumulation detected by flow cytometry. The KBv200 cell xenograft model was established to investigate the effect of PEDLLA-FG020326 on reversing MDR in vivo. RESULTS: PEDLLA-FG020326 and FG020326 exhibited 56.4- and 35.9-fold activity in reversing KBv200 cells to vincristine (VCR) resistance, respectively and 14.98- and 7.64-fold to Dox resistance, respectively. PEDLLA-FG020326 was much stronger than FG020326, resulting in the increase of Dox and Rh123 accumulation and the decrease of intracellular Dox extrusion in KBv200 cells. Importantly, PEDLLA-FG020326 exhibited more powerful activity than FG020326 in enhancing the effect of VCR against KBv200 cell xenografts in nude mice, but did not appear more toxic. CONCLUSION: The pharmacodynamics of FG020326 was improved by incorporating it into a micellar nanoparticle formed with PEG-block-PDLLA copolymers.