Here we report a novel example of a luminescent hydrogel, which is formed from silent individual molecules simply by altering the pH of the system. Formation of the emissive nanostructure is fully and repeatedly reversible. This hydrogel, with switchable luminescence, can potentially be used as a nano pH sensor.

The versatility of the fluorescent probes inspires us to design fluorescently traceable prodrugs, which enables tracking the drug delivery kinetics in living cells. Herein, we constructed a self-indicating nanoprodrug with two fluorescent moieties, an aggregation-induced emission molecule (tetraphenylethylene, TPE) and a luminant anticancer drug (doxorubicin, DOX), with a pH-responsive linker between them. Except when a low pH environment is encountered, an energy-transfer relay (ETR) occurs and inactivates the fluorescence of both, showing a dark background. Otherwise, the ETR would be interrupted and evoke a dual-color fluorogenic process, giving distinct fluorogenic read out. By observing the dual-color fluorogenic scenario, we captured the kinetics of the drug release process in living cells. Because the separated TPE and DOX are both fluorescent but have a distinct spectrum, by examining the spatiotemporal pattern of TPE and DOX, we were able to precisely disclose the drug-releasing site, the releasing time, the destinations of the carriers, and the executing site of the drugs at subcellular level. Furthermore, different intracellular drug release kinetics between free doxorubicin and its nanoformulations were also observed in a real-time manner.Keywords: aggregation-induced emission; dual-color responsive; FRET; nanoprodrug; pH sensitive;

In this work, 2-(2-aminoethoxy) ethanol-blocked phenylboronic acid-functionalized magnetic nanoparticles (blocked PMNPs) were fabricated for selective enrichment of different types of saccharides. The phenylboronic acid was designed for capturing the cis-diols moieties on saccharides molecules, and the 2-(2-aminoethoxy) ethanol can deplete the nonspecific absorption of peptides and proteins which always coexisted with saccharides. For mass spectrometry analysis, the PMNPs bound saccharides can be directly applied onto the MALDI plate with matrix without removing the PMNPs. By PMNPs, the simple saccharide (glucose) could be detected in pmol level. The complex saccharides can also be reliably purified and analyzed; 16 different N-glycans were successfully identified from ovalbumin, and the high-abundance N-glycans can be detected even when the ovalbumin was in very low concentration (2 μg). In human milk, ten different oligosaccharides were identified, and the lactose can still be detected when the human milk concentration was low to 0.01 μL.

A seedless method has been developed for the synthesis of high aspect ratio gold nanorods. Gold nanorods with a longitudinal surface plasmon resonance of larger than 1400 nm were synthesized in one step. The yield was high, and no purification step was needed. We also synthesized normal aspect ratio gold nanorods by a seedless method. The conditions for the synthesis of uniform gold nanorods with different width and aspect ratio by a seedless method were explored. A better understanding of the seedless method enables the facile synthesis of nanomaterials with a broader size tunability and better reproducibility.

In this study, an orally administered macrophage-targeting peptide delivery system was constructed through in situ self-assembly of Q11 peptide inside hollow glucan particles (GPs), which are approved by the FDA. The glucan shell efficiently protected the encapsulated peptide from enzymatic degradation in the gastrointestinal tract. β-1,3-(D)-Glucan is recognized by the membrane receptor dectin-1, which is highly expressed by intestinal antigen-presenting cells, including macrophages. GPs are thus efficiently phagocytized by intestinal macrophages. This study is applicable to the pharmaceutical industry for the development of orally delivered macrophage-targeting systems for effective and personalized remedies like immunotherapeutic vaccines.

The fluorescence of tetraphenylethylene (TPE), an archetypal luminogen, is induced by restriction of intramolecular rotation (RIR). TPE was grafted with palmitic acid (PA) onto a hydrophilic peptide to yield a cell membrane tracker named TR4. TR4 was incorporated into liposomes, where it showed significant RIR characteristics. When cells were incubated with TR4, cytoplasmic membranes were specifically labeled. TR4 shows excellent photostability and low cytotoxicity.Keywords: cell membrane; restriction of intramolecular rotation (RIR); tetraphenylethylene (TPE); tracker;

Nanoformulations show many therapeutic advantages over conventional formulations. We seek to develop traceable nanoformulations in order to closely monitor delivery. Herein, we developed a new drug delivery system (DDS) using tetraphenylethene (TPE) to fabricate a self-assembly micelle with aggregation-induced emission (AIE micelle). AIE makes the nanocarriers visible for high-quality imaging, and the switching on and off of the AIE is intrinsically controlled by the assembly and disassembly of the micelles. This DDS was tested for doxorubicin (DOX) delivery and intracellular imaging. For the DOX-loaded micelles (TPED), the DOX content reached as much as 15.3% by weight, and the anticancer efficiency was higher than for free DOX. Meanwhile, high-quality imaging was obtained to trace the intracellular delivery of the TPED.Keywords: aggregation-induced emission; drug delivery; imaging; self-assembly micelle; tetraphenylethene;

Tetraphenylethylene (TPE), an archetypal luminogen with aggregation-induced emission (AIE), was grafted to a salt-responsive peptide to yield a yet luminescent hydrogelator. After testing different parameters, we found that only in the presence of salt rather than temperature, pH, and solvent, did the monodisperse hydrogelators self-assemble into a hydrogel network with bright emission turned on. The induced luminescence was a dynamic change and enabled real time monitoring of hydrogel formation. Grating AIE molecules to stimuli-responsive peptides is a promising approach for the development of self-revealing soft materials for biological applications.Keywords: aggregation-induced emission (AIE); gelation-enhanced emission; luminescent hydrogel; salt-responsive; tetraphenylethylene (TPE);

Formation of T–Hg2+–T complexes changes the configuration of a single-stranded DNA, leading to enhanced fluorescence of an anchored cyanine-based probe that displays restricted intramolecular rotation (RIR)-induced emission. This label-free system can be used as a sensor for mercury ions with a detection limit of 4 nM.

The structural arrangement of amino acid residues in a native enzyme provides a blueprint for the design of artificial enzymes. One challenge of mimicking the catalytic center of a native enzyme is how to arrange the essential amino acid residues in an appropriate position. In this study, we designed an artificial hydrolase via self-assembly of short peptides to catalyze ester hydrolysis. When the assembled hydrolase catalytic sites were embedded in a matrix of peptide nanofibers, they exhibited much higher catalytic efficiency than the peptide nanofibers without the catalytic sites, suggesting that this well-ordered nanostructure is an attractive scaffold for developing new artificial enzymes. Furthermore, the cytotoxicity of the assembled hydrolase was evaluated with human cells, and the novel artificial biological enzyme showed excellent biocompatibility.Keywords: artificial enzyme; ester hydrolysis; hydrogel; nanofiber; self-assembly; short peptide;

Controlled drug loading and release into tumor cells to increase the intracellular drug concentration is a major challenge for cancer therapy due to resistance and inefficient cellular uptake. Here, a temperature and pH dual responsive PNiPAM/AA@SiO2 core–shell particles with internal controlled release were designed and fabricated for efficient cancer treatment, which could recognize the intrinsic pH differences between cancers and normal tissues. Upon lowering the temperature, doxorubicin was loaded into the PNiPAM/AA@SiO2 nanoparticles, whereas by increasing the acidity, previously loaded doxorubicin was quickly released. Comparing with common mesoporous silica particles (MSNs), these core–shell particles have a more uniform size and better dispersity. In addition, dried PNiPAM/AA@SiO2 nanoparticles could be easily redispersed in distilled water. The in vitro cell culture experiments showed that not only were PNiPAM/AA@SiO2 particles more biocompatible and less cytotoxic than MSN, but also DOX@PNiPAM/AA@SiO2 had a higher drug release efficiency in the lysosomes and a stronger inhibitory effect on tumor cell growth than DOX@MSN. All these features indicated that PNiPAM/AA@SiO2 particles have great potential in therapy applications.

Human α defensins human neutrophil peptide 1–3 (HNP 1–3) are potential prognostic cancer biomarkers. Metalloprotein anthrax lethal factor (ALF) binds to HNP 1–3 in a Zn2+-dependent manner. We conjugated ALF to the surface of magnetic nanoparticles (MNP) to magnetically isolate the HNPs, and used Zn2+ to control the capture and release HNPs.Keywords: anthrax lethal factor; defensin; magnetic nanoparticles; MALDI-TOF-MS;

A simple nanocarrier coated with chitosan and the pH-responsive charge-reversible polymer, PAH-Cit, was constructed using layer-by-layer assembly to deliver siRNA. Gold nanoparticles (AuNPs) were di-rectly reduced and stabilized by chitosan (CS), forming a positively charged AuNP-CS core. Charge-reversible PAH-Cit and polyethylenimine (PEI) were sequentially deposited onto the surface of AuNP-CS through electrostatic interaction, forming a PEI/PAH-Cit/AuNP-CS shell/core structure. After loading siRNA, the cytotoxicity of siRNA/PEI/PAH-Cit/AuNP-CS against HeLa and MCF-7R cells was negligible. This vehicle completely protected siRNA against enzymatic degradation at vector/RNA mass ratios of 2.5:1 and above. An in vitro release profile demonstrated an efficient siRNA release (79%) from siRNA/PEI/PAH-Cit/AuNP-CS at pH 5.5, suggesting a pH-induced charge-reversing action of PAH-Cit. This mechanism also worked in vivo and facilitated the escape of siRNA from endosomes. Using this carrier, the uptake of cy5-siRNA by HeLa cells was significantly increased compared to PEI, an efficient polycationic transfection reagent. In drug-resistant MCF-7 cells, specific gene silencing effectively reduced expression of MDR1, the gene encoding the drug exporter P-gp, and consequently promoted the uptake of doxorubicin. This simple charge-reversal polymer assembly nanosystem has three essential benefits (protection, efficient uptake, and facilitated escape) and provides a safe strategy with good biocompatibility for enhanced siRNA delivery and silencing.Keywords: charge-reversible; layer-by-layer assembly; siRNA

Here we report a novel example of a luminescent hydrogel, which is formed from silent individual molecules simply by altering the pH of the system. Formation of the emissive nanostructure is fully and repeatedly reversible. This hydrogel, with switchable luminescence, can potentially be used as a nano pH sensor.

A seedless method has been developed for the synthesis of high aspect ratio gold nanorods. Gold nanorods with a longitudinal surface plasmon resonance of larger than 1400 nm were synthesized in one step. The yield was high, and no purification step was needed. We also synthesized normal aspect ratio gold nanorods by a seedless method. The conditions for the synthesis of uniform gold nanorods with different width and aspect ratio by a seedless method were explored. A better understanding of the seedless method enables the facile synthesis of nanomaterials with a broader size tunability and better reproducibility.

Controlled drug loading and release into tumor cells to increase the intracellular drug concentration is a major challenge for cancer therapy due to resistance and inefficient cellular uptake. Here, a temperature and pH dual responsive PNiPAM/AA@SiO2 core–shell particles with internal controlled release were designed and fabricated for efficient cancer treatment, which could recognize the intrinsic pH differences between cancers and normal tissues. Upon lowering the temperature, doxorubicin was loaded into the PNiPAM/AA@SiO2 nanoparticles, whereas by increasing the acidity, previously loaded doxorubicin was quickly released. Comparing with common mesoporous silica particles (MSNs), these core–shell particles have a more uniform size and better dispersity. In addition, dried PNiPAM/AA@SiO2 nanoparticles could be easily redispersed in distilled water. The in vitro cell culture experiments showed that not only were PNiPAM/AA@SiO2 particles more biocompatible and less cytotoxic than MSN, but also DOX@PNiPAM/AA@SiO2 had a higher drug release efficiency in the lysosomes and a stronger inhibitory effect on tumor cell growth than DOX@MSN. All these features indicated that PNiPAM/AA@SiO2 particles have great potential in therapy applications.

In this study, an orally administered macrophage-targeting peptide delivery system was constructed through in situ self-assembly of Q11 peptide inside hollow glucan particles (GPs), which are approved by the FDA. The glucan shell efficiently protected the encapsulated peptide from enzymatic degradation in the gastrointestinal tract. β-1,3-(D)-Glucan is recognized by the membrane receptor dectin-1, which is highly expressed by intestinal antigen-presenting cells, including macrophages. GPs are thus efficiently phagocytized by intestinal macrophages. This study is applicable to the pharmaceutical industry for the development of orally delivered macrophage-targeting systems for effective and personalized remedies like immunotherapeutic vaccines.