Tannic Acid-Based Self-Assembling Nanocarriers with Antiphotobleaching and Controlled Releasing Properties for Collaborative Near-Infrared Photothermal/Photodynamic Therapy.

Near-infrared (NIR) organic materials have been widely developed for tumor phototherapy due to their deep tumor penetration, good biodegradability, and high photothermal conversion (PCE). However, most of the NIR organic dyes are easily destroyed by photooxidation due to their big and long conjugated structures, such as cyanine dyes. Under light irradiation, the reactive oxygen species (ROS) produced by these NIR dyes can easily break their conjugated skeleton, resulting in a dramatic decrease in phototherapeutic efficiency. Herein, an NIR organic dye cyanine dye (CyS) and a photosensitizer methylene blue (MB) were chosen to prepare nanocarrier CMTNPs by facile self-assembling with a natural antioxidant, tannic acid (TA). TA can greatly enhance the stability of NIR cyanine dyes by scavenging ROS. Furthermore, CMTNPs have a character of pH/thermal dual response, allowing for controlled release of MB in the slightly acidic tumor environment during photothermal therapy. The released MB can turn on both fluorescence and photodynamic therapy effects. In vitro and in vivo experiments demonstrated the remarkable tumor ablation ability of CMTNPs. Thus, our study provided an antiphotobleaching and controlled release photosensitizer strategy through the introduction of antioxidant TA into the nanocarrier for efficient collaborative photothermal/photodynamic therapy.

Dual-Responsive hollow mesoporous organosilicon nanocarriers for photodynamic therapy.

HYPOTHESIS: The nano-delivery platform, -SS-HMONs@MB@MnO2 nanoparticles (SMM NPs) loaded with methylene blue (MB) as photosensitizer have excellent photodynamic therapy (PDT) effect. The disulfide bond and MnO2 give the shell redox-responsive properties. SMM NPs consume glutathione (GSH) in tumor cells, reducing the scavenging of reactive oxygen species (ROS) by GSH and enhancing the PDT effect of MB. EXPERIMENTS: The GSH dual-responsive nano-delivery platform, was designed and constructed by using disulfide-doped hollow mesoporous organosilicon nanoparticles (-SS-HMONs) as intermediate responsive layer, loaded with MB as photosensitizer and coated with MnO2 as shells. The MB photosensitizer release and GSH response were characterized. The PDT effect of nanoparticles was evaluated. FINDINGS: The SMM NPs were uniform in size and well dispersed. The nanoparticles could react with GSH, leading to the decomposition of MnO2 shells and the breakage of disulfide bonds in -SS-HMONs, resulted in the release of MB photosensitizer. The cell experiment showed that SMM NPs had good ROS generating ability and PDT effect after being sucked by tumor cells, which could effectively kill tumor cells. However, in vivo experiments demonstrated that SMM NPs showed slight inhibition on tumor growth. The actual effect in animals was different from the effect in cells.

Exploring Linker-Group-Guided Self-Assembly of Ultrathin 2D Supramolecular Nanosheets in Water for Synergistic Cancer Phototherapy.

Water is ubiquitous in natural systems where it builds an essential environment supporting biological supramolecular polymers to function, transport, and exchange. However, this extreme polar environment becomes a hindrance for the superhydrophobic functional π-conjugated molecules, causing significant negative impacts on regulating their aggregation pathways, structures, and properties of the subsequently assembled nanomaterials. It especially makes the self-assembly of ultrathin two-dimensional (2D) functional nanomaterials by π-conjugated molecules a grand challenge in water, although ultrathin 2D functional nanomaterials have exhibited unique and superior properties. Herein, we demonstrate the organic solvent-free self-assembly of one-molecule-thick 2D nanosheets based on exploring how side chain modifications rule the aggregation behaviors of π-conjugated macrocycles in water. Through an in-depth understanding of the roles of linking groups for side chains on affecting the aggregation behaviors of porphyrins in water, the regulation of molecular arrangement in the aggregated state (H- or J-type aggregation) was attained. Moreover, by arranging ionic porphyrins into 2D single layers through J-aggregation, the ultrathin nanosheets (thickness ≈ 2 nm) with excellent solubility and stability were self-assembled in pure water, which demonstrated both outstanding 1O2 generation and photothermal capability. The ultrathin nanosheets were further investigated as metal- and carrier-free nanodrugs for synergetic phototherapies of cancers both in vitro and in vivo, which are highly desirable by combining the advantages and avoiding the disadvantages of the single use of PDT or PTT.

Antimicrobial protection of two controlled release silver nanoparticles on simulated silk cultural relic.

HYPOTHESIS: Silver nanoparticles coated with organic-inorganic hybrid silica or inorganic silica have antimicrobial ability, and the coating can also effectively improve the dispersion and stability of the particles. The slow release of silver ions (Ag+) can improve the antimicrobial activity of silver nanoparticles. The synthesized nanoparticles are light yellow, which does not affect the look and feel of the silk cultural relics and meets the requirements of the principle of minimum interference. EXPERIMENTS: Two kinds of silver-based nanoparticles were synthesized: silver core-shell nanoparticle (Ag@mSiO2) and silver yolk-shell nanoparticle (Ag@YSiO2). The morphology, surface properties and Ag+ release efficiency of two nanoparticles were characterized. The antimicrobial effects of two nanoparticles on Aspergillus niger (A. niger) and Penicillium citrinum (P. citrinum) were compared. FINDINGS: Both of Ag@mSiO2 and Ag@YSiO2 had uniform size and good stability. Two nanoparticles had pore structure and silver nanocore, which provided the basis for the dissolution and exchange of Ag+. Because more silver ions were released, Ag@mSiO2 had higher antimicrobial activity than Ag@YSiO2 for A. niger and P. citrinum. For various silk samples, Ag@mSiO2 exhibited excellent antimicrobial properties. Meanwhile, there was little change in the color and tearing strength of Ag@mSiO2 coated silk.

Integration of Activation by Hypoxia and Inhibition Resistance of Tumor Cells to Apoptosis for Precise and Augmented Photodynamic Therapy.

Photodynamic therapy (PDT) uses photosensitizers to convert oxygen (O2 ) to reactive oxygen species (ROS) under irradiation to induce DNA damage and kill cancer cells. However, the effect of PDT is usually alleviated by apoptosis resistance mechanism of tumor living cells. MTH1 enzyme is known to be such an apoptosis-resistance enzyme which is over expressed as a scavenger to repair the damaged DNA. In this work, a hypoxia-activated nanosystem FTPA, which can be degraded to release the encapsulated PDT photosensitizer 4-DCF-MPYM and an inhibitor TH588 is proposed. The inhibitor TH588 can inhibit the DNA repair process by reducing the activity of MTH1 enzyme, and achieve the purpose of amplifying the therapeutic effect of PDT. This work demonstrates that a precise and augmented tumor PDT is achieved by integration of hypoxia-activation and inhibition resistance of tumor cells to apoptosis.

A Selenium-Substituted Heptamethine Cyanine Photosensitizer for Near-Infrared Photodynamic Therapy.

Photodynamic therapy (PDT) is a relatively safe approach to cancer treatment without significant systemic side effects or drug resistance. However, the current PDT efficiency is unsatisfactory due to the lack of near-infrared (NIR) photosensitizers. Heptamethine cyanine (Cy7) dyes are well-known NIR fluorophores and are also used as photosensitizers. But their singlet oxygen quantum yields (ΦΔ ) are not ideal. Herein, we developed an NIR photosensitizer with a long-lived excited triplet state (τ=4.3 µs) by introducing a selenium atom into the structure of a Cy7 dye. The new NIR photosensitizer exhibits a significantly high singlet oxygen quantum yield (ΦΔ =0.11). Its good PDT effect was demonstrated in the living cells. Considering that the selenium-substituted photosensitizer has a very low dark cytotoxicity and good chemical stability, we conclude that it will have a promising future in biomedical and clinical applications.

Tuning the aqueous self-assembly of porphyrins by varying the number of cationic side chains.

Due to their excellent electronic and optical properties, porphyrins are extensively studied conjugated macrocycles in supramolecular chemistry for assembling functional nanomaterials. Although the aggregation of monomers plays a significant role in driving the self-assembly process into ordered nanostructures, it remains a challenge for tuning the self-assembling behavior of porphyrins through molecular structure modifications, especially in aqueous solutions. In the present work, two novel water-soluble porphyrin derivatives were synthesized by introducing cationic linear side chains into the π-conjugated core for phosphate-templated assembly through electrostatic interactions. It was found that the stacking patterns (H- or J-type aggregation) of porphyrins could be tuned by varying the number of side chains, which are associated with dramatic morphological change. The cytotoxicity and photodynamic properties of the J-aggregation-driven nano-assemblies were also investigated for the purpose of anti-cancer treatment. This study demonstrates a facile and effective strategy to regulate the aqueous self-assembling behavior of porphyrins that can impact the structure and properties of assembly, which will be of great benefit to the design and synthesis of functional nanomaterials for specific applications.

Synthesis of Noble Metal M@YSiO2 Yolk-Shell Nanoparticles with Thin Organic/Inorganic Hybrid Outer Shells via an Aqueous Medium Phase.

A simple method is proposed for the synthesis of noble metal M@YSiO2 (M = Au, Pd, Ag) yolk-shell nanoparticles. The effects of synthesis conditions on the preparation of yolk-shell nanoparticles were discussed in detail. According to the different corrosion resistances between inorganic silica and organosilicone in a selective etching solution, yolk-shell nanoparticles with large cavity and thin shell were prepared using the same aqueous medium in a step-by-step synthesis process. Different from traditional methods, this method is facile and efficient because the main synthesis process is carried out in an aqueous phase. This extended method may benefit the synthesis and application of other nanomaterials with a similar yolk-shell structure.

Au@mSiO2 core-shell nanoparticles loaded with fluorescent dyes: synthesis and application for imaging performance.

Here, Au@mSiO2 core-shell nanoparticles were easily synthesized by a one-pot method. Positively charged alkyl chains with different lengths were modified on the surface of the particles. Thus composite nanoparticles with different potentials and hydrophilic interface properties were prepared. Based on the charge properties of the shell surface, the process of loading dyes was simplified by the strong electrostatic adsorption between the particle surface and the heterogeneous negatively charged dyes. The fluorescence intensity and fluorescence lifetime of the loaded fluorescent dyes showed that the dyes could not produce effective tunneling in the mesoporous materials, which was limited to the surface of the particles, which is beneficial for the subsequent research on the loading or release of nanoparticles. After loading, the nanoparticles still exhibit a high fluorescence intensity, enabling dual-mode microscopic imaging (TEM and fluorescence).

Ambient temperature fabrication of a covalent organic framework from 1,3,5-triformylphloroglucinol and 1,4-phenylenediamine as a coating for use in open-tubular capillary electrochromatography of drugs and amino acids.

A covalent organic framework (COF) named TpPa-1 was designed and synthesized at ambient temperature by an ultrasound-assisted method from 1,3,5-triformylphloroglucinol (Tp) and 1,4-phenylenediamine (Pa-1). It was utilized as a stationary phase in open-tubular capillary electrochromatography (OT-CEC). The column was coated with TpPa-1 using a covalent bonding strategy. The coated capillary was characterized by morphology, crystallography, and mesoporous analysis to confirm the successful fabrication. The OT-CEC method was utilized for the analysis of tetracyclines, sulfonamides, cephalosporins and amino acids with high-resolution (Rs > 1.81) and good precision (RSD < 4.9%). It takes about 12 h from COF preparation to OT-CEC separation. Graphical abstract A covalent organic framework (COF) named TpPa-1 was synthesized at ambient temperature by an ultrasound-assisted method from 1,3,5-triformylphloroglucinol (Tp) and 1,4-phenylenediamine (Pa-1). COF-TpPa-1 modified capillary column was utilized for the analysis of tetracyclines, sulfonamides, cephalosporins and amino acids with high-resolution and good precision.

Evaluation of porcine circovirus type 2 infection in in vitro embryo production using naturally infected oocytes.

In vitro fertilization (IVF) and somatic cell nuclear transfer (SCNT) are important breeding techniques for livestock. High-quality MII oocytes produced from in vitro maturation (IVM) are required for the two techniques listed above. The ovaries used for IVM operations are primarily acquired from commercial abattoirs, and the pathogen status of slaughtered animals becomes an unavoidable issue. Our previous monitoring data showed that porcine circovirus type 2 (PCV-2) is the main pathogen present in ovaries from abattoirs. However, the characteristics and effects of PCV-2 infection in oocyte maturation and in vitro production (IVP) of embryos are unclear, and currently there are no relevant studies. Therefore, the aim of this study was to determine the PCV-2 infection pattern and determine whether it affects oocyte in vitro maturation and IVP embryo development. More than five hundred ovaries and five thousand oocytes were utilized in the present study. Polymerase chain reaction (PCR) was used to detect PCV-2 DNA in ovaries, follicular fluid (FF), oocytes, cumulus cells and IVP embryos. The effects of viral infections on the rate of oocyte maturation and IVP embryo development were evaluated. We also analyzed the number of copies of the virus in the IVM and IVP process by absolute quantitative fluorescence PCR. Our study showed that the prevalent virus subgenotype in ovaries was PCV-2a. PCV-2a infection did not significantly affect ovarian/oocyte morphology and maturation. Moreover, virus infection did not have a significant effect on the development of the IVP embryos except for a reduction in IVF blastocyst cell numbers. Further tests showed that the viral copy numbers fluctuated at different stages between the IVP embryos and culture medium. For the first time, this study identified the infection pattern of naturally sourced PCV-2 in the course of oocyte maturation and embryo development.