An Integrated Design of a Polypseudorotaxane-Based Sea Cucumber Mimic.

The development of integrated systems that mimic the multi-stage stiffness change of marine animals such as the sea cucumber requires the design of molecularly tailored structures. Herein, we used an integrated biomimicry design to fabricate a sea cucumber mimic using sidechain polypseudorotaxanes with tunable nano-to-macroscale properties. A series of polyethylene glycol (PEG)-based sidechain copolymers were synthesized to form sidechain polypseudorotaxanes with α-cyclodextrins (α-CDs). By tailoring the copolymers' molecular weights and their PEG grafting densities, we rationally tuned the sizes of the formed polypseudorotaxanes crystalline domain and the physical crosslinking density of the hydrogels, which facilitated 3D printing and the mechanical adaptability to these hydrogels. After 3D printing and photo-crosslinking, the obtained hydrogels exhibited large tensile strain and broad elastic-to-plastic variations upon α-CD (de)threading. These discoveries enabled a successful fabrication of a sea cucumber mimic, demonstrating multi-stage stiffness changes.

Photoinduced Reversible Morphological Transformation of Azobenzene-Containing Pseudo-2D Polymers.

2D polymer sheets containing azobenzene are successfully prepared by a facile strategy of "2D self-assembly polymerization (2DSP)" via free radical polymerization in solution. A bola amphiphile containing azobenzene as a novel monomer is designed and synthesized. The results indicate that single-layer covalent pseudo-2D polymers on a micrometer scale are obtained after polymerization with vinyl monomers. Moreover, the 2D polymer sheets are highly sensitive to UV light due to incorporation of azobenzene groups into the polymer. Upon alternative irradiation with UV and visible light, the morphological transformation between sheets and rolled-up nanotubes can be achieved based on the reversible trans-to-cis photoisomerization of azobenzene units in the 2D polymer sheets.

Placenta-anchored tadalafil liposomes rescues intrauterine growth restriction through continuous placental blood perfusion improvement.

Physiological or pathological hypoperfusion of the placenta is one of the main causes of intrauterine growth restriction (IUGR) which poses a significant risk to the health of the fetus and newborn. Tadalafil, a 5-type phosphodiesterase inhibitor, has previously been found to improve the symptoms of IUGR in various clinical studies. Unfortunately, its clinical utility is hindered by its limited water solubility, rapid metabolism, and lack of specific distribution in target tissues rendering tadalafil unable to maintain long-term placental perfusion. In this study, iRGD-modified tadalafil-loaded liposomes (iRGD-lipo@Tad) featuring a size of approximately 480 nm were designed to rectify the shortcomings of tadalafil. The prepared iRGD-lipo@Tad exhibited superior stability, sustained drug release capacity, and low cytotoxicity. The fluorescence study, tissue slice study, and drug biodistribution study together demonstrated the placenta-anchored ability of iRGD-modified liposomes. This was achieved by a dual approach consisting of the iRGD-mediated placenta-targeting effect and special particle size-mediated placenta resident effect. The pharmacokinetic study revealed a significant improvement in the in vivo process of tadalafil encapsulated by the iRGD-modified liposomes. In comparison to the tadalafil solution, the peak plasma concentration of iRGD-lipo@Tad was significantly increased, and the area under the curve was increased by about 7.88 times. In the pharmacodynamic study, iRGD-lipo@Tad achieved a continuous and efficient improvement of placental blood perfusion. This was achieved by decreasing the ratio of plasma soluble fms-like tyrosine kinase to placental growth factor and increasing the levels of cyclic guanosine monophosphate and nitric oxide. Consequently, iRGD-lipo@Tad resulted in a significant increase in embryo weight and a reduction in the miscarriage rate of N-Nitro-L-arginine methyl ester-induced IUGR pregnant mice without detectable toxicity. In summary, the nanotechnology-assisted therapy strategy presented here not only overcomes the limitations of tadalafil in the clinical treatment of IUGR but also offers new avenues to address the treatment of other placenta-originated diseases.

Size-dependent placental retention effect of liposomes in ICR pregnant mice: Potential superiority in placenta-derived disease therapy.

The great challenge in developing safe medications for placenta-derived diseases is to reduce or eliminate fetal drug exposure while still providing the necessary therapeutic effect. Rapid advances in nanotechnology have brought opportunities for the therapy of placenta-derived disease through accumulating the drug in the placenta while reducing its placental penetration. Among various nanocarriers, liposomes are regarded as an ideal type of carrier for placental drug delivery due to their biosafety and biodegradability. However, their placental retention effect with different particle sizes has not been studied. This research aimed to explore a suitable size of liposomes for placenta drug delivery. Cy 5 dye was chosen as a model molecule for tracing the distribution of three different-sized liposomes (∼80 nm, 200 nm, and 500 nm) in ICR pregnant mice. The stability, cytotoxicity, and cellular uptake study of Cy 5-loaded liposomes were performed. The in vivo fluorescence studies on ICR pregnant mice suggested that the particle size of liposomes was positively correlated with the degree of liposome aggregation in the placenta. The ratio of fluorescence in the placenta and fetus section (P/F value) was proposed to evaluate the placental retention effect of different-sized liposomes. The results showed that the liposomes with 500 nm had the highest P/F value and thus exhibited the strongest placental retention effect and the weakest placental penetration ability. Moreover, liquid chromatography-mass spectrometry analysis confirmed the reliability of the fluorescence section analysis in exploring the placental retention effect of nanovehicles. In general, this study introduced a simple and intuitive method to evaluate the placental retention effect of nanoplatforms and defined a suitable size of liposomes for placenta-derived disease drug delivery.

Cellulose nanocrystals concentration and oil-water ratio for solid-liquid controllable emulsion polymerization.

Stabilities of cellulose Pickering emulsions are of great importance to utilize them effectively, but influenced by their complex compositions, such as, colloidal particles, oil phases and water phases. In this work, solid-liquid controllable polymerization products could obtain by adjusting cellulose nanocrystals (CNCs) concentration and vinyl acetate (VAc)-water ratio. The emulsions in zone Ӏ (w/o) and II (o/w) of the three-phase diagram were selected for researching. The polymerization emulsions in zone II illustrated the o/w ratio played a more important role than CNCs concentration in the storage stability and practicality of the polymerized emulsion; The polymer in zone Ӏ showed a large number of porous structures. This is an innovative method that different forms of target products are obtained through the guidance of three-phase diagram, which not only broadens the application field, but also applies to other Pickering emulsion systems.

Atmospheric Low-Temperature Plasma-Induced Changes in the Structure of the Lignin Macromolecule: An Experimental and Theoretical Investigation.

Atmospheric low-temperature plasma has emerged as a promising pretreatment for lignocellulose to improve bio-refining. Herein, we investigated plasma-induced changes in the chemical structure of lignin to obtain a fundamental understanding of the plasma-lignocellulose interaction. Based on the results, plasma possesses a strong capacity to cleave C-C covalent bonds in the aliphatic region of lignin, accompanied by oxidation. Plasma treatment leads to the degradation and fragmentation of lignin. Pronounced deconstruction of ß-O-4 aryl ether is observed in plasma. The relative content of ß-O-4 aryl ether was reduced from the initial value of 65.1/100Ar to 58.7/100Ar for lignin from corncob and from the initial value of 72.5/100Ar to 63.8/100Ar for lignin from poplar after plasma treatment, respectively. According to the density functional theory analysis, the oxygen atom of ß-O-4 aryl ether is the most likely potential reaction site and the Cß-O covalent bond exhibits the lowest decomposition free energy (50.5 kcal mol-1), which will easily be cleaved in plasma. The dominant reaction pathway of lignin degradation is the cleavage of the Cß-O covalent bond followed by the cleavage of the Cß-Cα bond. We propose that this investigation is beneficial to optimize and expand the applications of plasma treatment in pretreatment of lignocellulose.

What Are the Major Physicochemical Factors in Determining the Preferential Nuclear Uptake of the DNA "Light-Switching" Ru(II)-Polypyridyl Complex in Live Cells via Ion-Pairing with Chlorophenolate Counter-Anions?

Delivering potential theranostic metal complexes into preferential cellular targets is becoming of increasing interest. Here we report that nuclear uptake of a cell-impermeable DNA "light-switching" Ru(II)-polypyridyl complex can be significantly facilitated by chlorophenolate counter-anions, which was found, unexpectedly, to be correlated positively with the binding stability but inversely with the lipophilicity of the formed ion pairs.