Erratum: Dual-Targeted Gold Nanoprism for Recognition of Early Apoptosis, Dual-Model Imaging and Precise Cancer Photothermal Therapy: Erratum.

[This corrects the article DOI: 10.7150/thno.34755.].

Dual-Targeted Gold Nanoprism for Recognition of Early Apoptosis, Dual-Model Imaging and Precise Cancer Photothermal Therapy.

Photothermal therapy as novel strategy to convert near-infrared (NIR) light into heat for treatment cancers has attracted great attention and been widely studied. However, side effects and low efficiency remain the main challenge of precise cancer photothermal therapy. Methods: In this study, we have successfully fabricated and characterized the dual-targeted gold nanoprisms, whereby bare gold nanoprisms (Au NPR) were conjugated to a phenanthroline derivatives-functionalized tetraphenylethene (TPE) and further stabilized with target peptide aptamers via Au-S bonds (Au-Apt-TPE). Then, the remaining nitrogen atoms of the Au-Apt-TPE could effectively chelate with Zn2+ ions (Au-Apt-TPE@Zn) for monitoring early stage apoptotic cells. Results: The as-synthesized Au-Apt-TPE@Zn exhibited good monodispersity, size stability and consistent spectral characteristics. TPE synthesized here showed aggregation-induced emission (AIE) characteristics, and zinc conjunction (TPE@Zn) endowed Au-Apt-TPE@Zn with the cell membrane-targeted ability to selectively recognize the membranes of early stage apoptotic cells but not respond to healthy cells, which provided valuable diagnosis information on therapeutic efficacy. Au-Apt-TPE@Zn achieved specifically nuclear-targeted ability by surface decoration of AS1411 DNA aptamer. Au-Apt-TPE@Zn under NIR irradiation showed effective photothermal therapy against SGC-7901 human gastric carcinoma cells growth in vitro by inducing apoptosis through triggering reactive oxygen species (ROS) overproduction and regulating multiple signal crosstalk. In vivo studies revealed that Au-Apt-TPE@Zn under NIR irradiation showed deep penetration and dual-model imaging application (cancer-targeted fluorescence imaging and light-up photoacoustic imaging). Au-Apt-TPE@Zn under NIR irradiation also displayed strong photothermal therapy against gastric carcinoma xenograft growth in vivo by induction of apoptosis. Importantly, analysis of histopathology, hematotoxicity and immunocytotoxicity indicated that Au-Apt-TPE@Zn had less side effect and high biocompatibility. Conclusions: Our findings validated the design of using Au nanoprism with AIE materials and dual-targeted decoration could be an effective strategy in recognition of early apoptosis, dual-model imaging and precise cancer photothermal therapy.

Chitosan-catechin coating as an antifungal and preservable agent for postharvest satsuma oranges.

The antifungal properties of chitosan-catechin coating and the effect of fruit preservation were studied. We used catechin to modify chitosan to prepare a coating. The purpose of the study was to use chitosan-catechin coating to prolong the preservation time of satsuma oranges. In vitro experiments, the results showed that the antifungal activity of chitosan-catechin increased with increasing concentration, and the results are also significantly effect of comparing to chitosan and catechin alone (*p < 0.05). In vivo studies, chitosan-catechin coating treatment significantly reduced rot caused by Penicillium Citrinum and Aspergillus niger. The physiological and biochemical indexes of the chitosan-catechin coating treatment group were significantly higher than those of the control group (*p ≤ 0.05). In the toxicity test, mice injected with chitosan-catechin solution showed no significant difference compared to the control group. These results indicate that this chitosan-catechin coating may be useful as an antifungal and preserving agent for satsuma oranges. PRACTICAL APPLICATIONS: The fruit after harvest every year is a large loss due to improper storage, and the preservation of fruits is an effective way to reduce losses. The traditional fruit wrap is not degradable, and the preservation effect is relatively general. The chitosan film is a new type of edible fruit wrap, which has the advantages of being edible and easily degradable, and can effectively reduce environmental pollution. Adding catechin to the preparation process of chitosan film can better improve the fresh-keeping effect and prolong the preservation time of the fruit.

Ecofriendly Electrospun Membranes Loaded with Visible-Light-Responding Nanoparticles for Multifunctional Usages: Highly Efficient Air Filtration, Dye Scavenging, and Bactericidal Activity.

Ambient particulate matter pollution has posed serious threats to global environment and public health. However, highly efficient filtration of submicron particles, the so-named "secondary pollution" caused by, e.g., bacterial growth in filters and the use of nondegradable filter materials, remains a serious challenge. In this study, poly(vinyl alcohol) (PVA) and konjac glucomannan (KGM)-based nanofiber membranes, loaded with ZnO nanoparticles, were prepared through green electrospinning and ecofriendly thermal cross-linking. Thus obtained fibrous membranes not only show highly efficient air-filtration performance but also show superior photocatalytic activity and antibacterial activity. The filtration efficiency of the ZnO@PVA/KGM membranes for ultrafine particles (300 nm) was higher than 99.99%, being superior to that of commercial HEPA filters. By virtue of the high photocatalytic activity, methyl orange was efficiently decolorized with a removal efficiency of more than 98% at an initial concentration of 20 mg L-1 under 120 min of solar irradiation. A multifunctional membrane with high removal efficiency, low flow resistance, superior photocatalytic activity, and superior antibacterial activity was successfully achieved. It is conceivable that the combination of a biodegradable polymer and an active metal particle would form an unprecedented photocatalytic system, which will be quite promising for environmental remediation such as air filtration and water treatment.

Molybdenum disulfide nanosheets loaded with chitosan and silver nanoparticles effective antifungal activities: in vitro and in vivo.

A method was developed for the liquid exfoliation of molybdenum disulfide (MoS2) from its bulk materials using ultrasound in aqueous phase with the assistance of chitosan (CS) and silver nanoparticles (Ag NPs) for effective loading of a variety of therapeutic molecules. The characterization results revealed that the as-made chemically-exfoliated MoS2 nanosheets had an average thickness of ∼10 nm. The new material, CS and Ag NPs-modified MoS2 (MoS2-CS-Ag), showed highly effective antifungal activities against Saccharomyces uvarum and Aspergillus niger. The Ag NPs-loaded MoS2 nanosheets achieved outstanding antifungal effect by inhibiting fungal growth both in vitro and in vivo. Notably, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis of spore morphological changes caused by MoS2-CS-Ag treatment reveal that it may directly cause the cell death. The result of the analysis of the application of MoS2-CS-Ag as an antifungal for fruits also demonstrated the MoS2-CS-Ag protective properties against fungi. The excellent film-forming ability of CS has been shown to contribute to the effectiveness of MoS2-CS-Ag in preserving the freshness of fruits, exhibited in four chemical quality sections: Vc, total carbohydrate, weight loss, and titratable acidity in fruit preservation application assay. The present study reports a new and exciting insight in a multi-functional drug carrier for protecting postharvest fruit.

Transcriptome Analysis Reveals Silver Nanoparticle-Decorated Quercetin Antibacterial Molecular Mechanism.

Facile and simple method is developed to synthesize silver-nanoparticle-decorated quercetin nanoparticles (QA NPs). Modification suggests that synergistic quercetin (Qe) improves the antibacterial effect of silver nanoparticles (Ag NPs). Characterization experiment indicates that QA NPs have a diameter of approximately 10 nm. QA NPs show highly effective antibacterial activities against drug-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). We explore antibacterial mechanisms using S. aureus and E. coli treated with QA NPs. Through morphological changes in E. coli and S. aureus, mechanisms are examined for bacterial damage caused by particulate matter from local dissociation of silver ion and Qe from QA NPs trapped inside membranes. Moreover, we note that gene expression profiling methods, such as RNA sequencing, can be used to predict discover mechanisms of toxicity of QA NPs. Gene ontology (GO) assay analyses demonstrate the molecular mechanism of the antibacterial effect of QA NPs. Regarding cellular component ontology, "cell wall organization or biogenesis" (GO: 0071554) and "cell wall macromolecule metabolic process" (GO: 0044036) are the most represented categories. The present study reports that transcriptome analysis of the mechanism offers novel insights into the molecular mechanism of antibacterial assays.

Quercetin loading CdSe/ZnS nanoparticles as efficient antibacterial and anticancer materials.

Quercetin (Qe) plays an important role in inflammation, antibacterial, anticancer, and aging. However, Qe has extremely low water solubility, which is a major challenge in drug absorption. In this study, we described a simple method for synthesis of Qe/CdSe/ZnS nanoparticles (QCZ NPs). The QCZ NPs had an average diameter of 10nm and prominent yellow emission under UV irradiation. We investigated the antibacterial activity of QCZ NPs against drug-resistant Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) in vitro. Results showed that QCZ NPs had considerably more effective antibacterial activities than Qe or CdSe nanoparticles (CdSe NPs). Antibacterial experiment results showed that QCZ NPs acted against E. coli and B. subtilis by disrupting the bacterial cell wall and membrane. In vivo study, the QCZ NPs could cure inflammation and lesion which caused by E. coli. In anticancer assays, the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cell proliferation assays exhibited the cytotoxicity of QCZ NPs increased approximately 2-6 fold compared to raw Qe and CdSe NPs. Moreover, by using RT-CES (real-time cell electronic sensing) studies, we had demonstrated QCZ NPs have also an effect on migration and proliferation of BGC-823 cells. CdSe NPs loaded with Qe, these QCZ NPs exhibited excellent antibacterial (E. coli and B. subtilis) and anticancer (BGC-823) activities.

Design of PLGA-functionalized quercetin nanoparticles for potential use in Alzheimer's disease.

Dysfunctional interaction of amyloid-ß (Aß) with excess metal ions is proved to be related to the etiology of Alzheimer's disease (AD). Hence, disruption of these metal-peptide interactions using nanoparticles (NPs) holds considerable promise as a therapeutic strategy to combat this incurable disease. Given that quercetin is a natural product, the biocompatibility and small size essential for permeating the blood-brain barrier make it a potential therapeutic drug candidate for treating AD. Nanocarriers formulated with the US Food and Drug Administration-approved biocompatible and biodegradable polymer PLGA are being widely explored for the controlled delivery of therapeutic drugs, proteins, peptides, oligonucleotides, and genes. With this background, the present study was undertaken to investigate the effects of PLGA-functionalized quercetin (PLGA@QT) NPs on inhibited and disassembled Aß42 fibrils and the PLGA@QT NPs have low cytotoxicity when tested on SH-SY5Y cells in vitro. As expected, the cytotoxicity studies of the PLGA@QT NPs led to a concentration-related behaviour on the SH-SY5Y human neuroblastoma cells. And, it has demonstrated that PLGA@QT NPs can inhibit the neurotoxicity of Zn2+-Aß42 system and enhance the viability of neuron cells. The results from behavioral tests indicate that injection of PLGA@QT NPs into APP/PS1 mice ameliorate cognition and memory impairments. Most encouragingly, the in vivo systemic toxicity of PLGA@QT NPs examined by histological analysis in major organs did not show any signs of adverse effect to mice. Thus, the prepared quercetin based nanoscale drug delivery carrier efficiently enhanced the therapeutic index and reduced the side effects. Our findings are highly encouraging, providing substantial evidence of the safety of PLGA@QT NPs for biomedical application. We expect these findings will be relevant for other NPs for treatment of AD and have broad implications in NP-based studies and applications.

Anti-tumor activity and mechanism of apoptosis of A549 induced by ruthenium complex.

Two new ruthenium (II) polypyridyl complexes [Ru(MeIm)4(pip)]2+ (1) and [Ru(MeIm)4(4-npip)]2+ (2) were synthesized under the guidance of computational studies (DFT). Their binding property to human telomeric G-quadruplex studied by UV-Vis absorption spectroscopy, the fluorescent resonance energy transfer (FRET) melting assay and circular dichroism (CD) spectroscopy for validating the theoretical prediction. Both of them were evaluated for their potential anti-proliferative activity against four human tumor cell lines. Complex 2 shows growth inhibition against all the cell lines tested, especially the human lung tumor cell (A549). The RTCA analysis not only validated the inhibition activity but also showed the ability of reducing A549 cells' migration. DNA-flow cytometric analysis, mitochondrial membrane potential (ΔΨm) and the scavenger measurements of reactive oxygen species (ROS) analysis carried out to investigate the mechanism of cell growth inhibition and apoptosis-inducing effect of complex 2. The results demonstrated that complex 2 induces tumor cells apoptosis by acting on both mitochondrial homeostasis destruction and death receptor signaling pathways. And those suggested that complex 2 could be a candidate for further evaluation as a chemotherapeutic agent against human tumor.

Silver nanoparticles-quercetin conjugation to siRNA against drug-resistant Bacillus subtilis for effective gene silencing: in vitro and in vivo.

Quercetin (Qe) exhibited extremely low water solubility, and thus, it was modified using silver nanoparticles (AgNPs). We fabricated AgNPs combined with Qe (AgNPs-Qe). The modification suggested that the synergistic properties of Qe enhanced the antibacterial activity of AgNPs. However, AgNPs-Qe exerted no effect on many kinds of drug-resistant bacteria, including Pseudomonas aeruginosa and Bacillus subtilis. RNA interference has considerable therapeutic potential because of its high specificity and potential capability to evade drug resistance. Therefore, we stabilized AgNPs-Qe with a layer of molecules (siRNA). The newly fabricated nanoparticles exerted improved effect on many kinds of bacteria, including the most prominent drug-resistant species B. subtilis. Agarose gel electrophoresis showed that the highest critical nitrogen-to-phosphorus (N/P) ratio occurred at a vector/siRNA with a w/w ratio of 7:1. Characterization experiment indicated that the diameter of siRNA/AgNPs-Qe was approximately 40 nm (40 ± 10 nm). Moreover, AgNPs-Qe were stabilized with a layer of siRNA that was approximately 10nm thick. Results of the in vitro study suggested that siRNA/AgNPs-Qe could destroy the cell wall and inhibit bacterial propagation. Meanwhile, the in vivo experiment on the animal bacteremia model, as well as the optical imaging of nude mice and their isolated organs, demonstrated that bacteria accumulated in the blood, heart, liver, spleen, lungs, and kidneys after the intravenous injection of B. subtilis. The bacteria in the blood and organs, as well as the inflamed cells in the tissues, gradually decreased after the mice received intravenous tail injection of siRNA/AgNPs-Qe for treatment. Both the in vitro and the in vivo studies exhibit that siRNA/AgNPs-Qe can be a potential nanoscale drug delivery system for B. subtilis targeting bacterimia.