Dual-Responsive Micelles with Aggregation-Induced Emission Feature and Two-Photon Aborsption for Accurate Drug Delivery and Bioimaging.

Intelligent polymeric micelles provide great potential for accurate cancer theranostics. Herein, gemcitabine (GEM)-conjugated redox-responsive prodrug micelles based on a pH-responsive charge-conventional PMPC-b-P (DEMA-co-SS-GEM-co-TPMA) copolymer and a two-photon absorbing aggregation-induced emission (AIE) fluorescence probe have been developed for lysosome-targeted drug release and bioimaging. The multifunctional copolymer has been synthesized via RAFT polymerization, and GEM is conjugated to the copolymer via GSH-cleavable disulfide bonds. These GEM-conjugated micelles exhibit great pH responsiveness at pH 5.0, while being stable at pH 6.0. GSH-triggered drug release can be observed with the GSH concentration increased from 0 to 10 mM. Moreover, the high-quality AIE-active two-photon imaging is confirmed by cell and deep-tissue imaging. More importantly, the distribution of these nanocarriers can be traced because of the AIE feature of the micelles. Along with good in vitro and in vivo tumor-suppression ability and significantly reduced side effects, this smart two-photon AIE micelle would be a potential candidate for cancer diagnosis and therapy.

A pore-scale investigation of microplastics migration and deposition during unsaturated flow in porous media.

Microplastics are ubiquitous in the natural environment and have the potential to endanger the natural environment, ecology and even human health. A series of microfluidic experiments by using soft lithography technology were carried out to investigate the effect of flow rate, particle volume fraction, particle size and pore/throat ratio on microplastics migration and deposition at the pore scale. We discovered a range of deposition patterns of the spherical microplastics from no particle deposition, to discontinuous particle layer, and to continuous particle layers in the retained liquid in the pores, depending on the particle size and volume fraction. Several metrics, including air saturation, probability of particle detainment, expansion ratio and thickness of residual liquid, were quantified to examine the role of various parameters on particle migration and retention of microplastics. At low flow rate (Q = 0.05 µL/min), microplastics migration and deposition were sensitive to changes in particle volume fraction, particle size and pore/throat ratio. In contrast, at high flow rates (Q > 5 µL/min), the migration and retention of particles were mainly controlled by strongly channelized air invasion pattern, while the particle volume fraction, particle size and pore/throat size ratio have only secondary influence. At intermediate range of flow rates, microplastics migration and deposition were dramatically impacted by flow rate, particle volume fraction, particle size and pore/throat ratio. This work improves the understanding of the mechanisms of particle migration and retention in porous media and can provide a reference for more accurate assessment of the exposure levels and times of microplastics in soil and groundwater systems.

Mitigation of ultrafiltration membrane fouling by a simulated sunlight-peroxymonosulfate system with the assistance of irradiated NOM.

Oxidation pretreatments prior to ultrafiltration are hindered by the need for energy input and sludge disposal. Herein, a simulated sunlight-induced natural organic matter (NOM) for peroxymonosulfate (PMS) activation was used as pretreatment to alleviate ultrafiltration membrane fouling caused by NOM itself in the Songhua River water. When light intensity was over 100 mW/cm2, the pretreatment removed NOM effectively, characterized with UV254, dissolved organic carbon (DOC) and maximum fluorescent intensity (Fmax), and improved filtration flux. At 200 mW/cm2 light intensity and 0.5 mM PMS, 57.5% of UV254 and 18.5% of DOC were removed, and humic-like fluorescent component was degraded by 84%-94% while ∼60% for protein-like substance. Membrane flux was increased by 94%, and reversible and irreversible fouling resistances were reduced by 62.4% and 51.9%, respectively. Both total fouling index (TFI) and hydraulic irreversible fouling index (HIFI) were moderately correlated with the DOC, whereas they prominently correlated with the UV254 and the Fmaxs of all fluorescence components, which could be served as key indicators to predict and control membrane fouling. Mathematical modeling showed that the pretreatment alleviated the fouling in the membrane pores and cake layer. The simulated sunlight-induced NOM (3NOM* and eaq¯) could activate PMS to form active species, which enabled to oxidize high molecular weight (MW) substances and mineralize low MW compounds in NOM as well as hinder their linking with inorganic cations, thereby reducing organic and inorganic membrane fouling simultaneously. This study may provide a new strategy for decentralized potable water treatment, especially in a single household or community.

Inorganic-polymerization crosslinked tissue-siloxane hybrid as potential biomaterial for bioprosthetic heart valves.

Bioprosthetic heart valve (BHV) replacement is increasingly used for treating valve-related diseases worldwide but the current commercially used BHVs treated with glutaraldehyde (Glut) often failed within 12-15 years due to degradation, thrombosis, inferior biocompatibility, and calcification. Herein, 3-glycidyloxypropyl trimethoxysilane (GPTMS) was used to crosslink porcine pericardium (PP) at the concentration (vol/vol) of 0.25%, 1%, 2%, and 4% and their performance for potential application in BHVs was evaluated. The crosslinking mechanism mainly involved the ring-opening of epoxide by amine attack and silanol poly-condensation. The stability of collagen in higher concentration (1%, 2%, and 4%) GPTMS crosslinked PPs (GPTMS-PPs) was clearly increased. GPTMS-PPs showed no cytotoxicity and supported the growth of endothelial cells while Glut-PP did not. GPTMS-PPs were less prothrombotic than Glut-PP. GPTMS-PP crosslinked at 1% concentration showed comparable mechanical properties to Glut-PP while had better anti-tearing performance. The subcutaneous implantation in rat for 30 days showed that GPTMS crosslinking was able to effectively inhibit the calcification of BHV.

A method for simultaneously crosslinking and functionalizing extracellular matrix-based biomaterials as bioprosthetic heart valves with enhanced endothelialization and reduced inflammation.

With the coming of an aging society and the emergence of transcatheter valve technology, the implantation of bioprosthetic heart valves (BHVs) in patients with valvular disease has significantly increased worldwide. Currently, most clinically available BHVs are crosslinked with glutaraldehyde (GLUT). However, the GLUT treated BHV is less durable due to the combined effect of multiple factors such as cytotoxicity, immune responses, and calcification. In this study, the in-situ polymerization of sulfonic monomers with a decellularized extracellular matrix (ECM) was performed to simultaneously achieve the crosslinking and functionalization of ECM. Subsequently, the feasibility of the hybrid ECM used as leaflet material of BHV was evaluated. In in-vitro tests, the results indicated that the hybrid ECM fixed collagen efficiently and the introduction of sulfonic polymer promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs). In in-vivo tests, after being implanted in SD rats and mice, the hybrid ECM significantly inhibited immune response and calcification compared with the non-hybrid counterpart and GLUT crosslinked tissue. These results indicated that the hybrid ECM exhibited more competitive stability and better biocompatibility compared to these features in GLUT-crosslinked valve. Therefore, the sulfonic polymer hybrid ECM provides a potential material for more durable BHV and the in-situ polymerization strategy can serve as a general treatment method for tissue crosslinking as well as tailoring the biophysical properties of ECM.

A New Silicon Dioxide-Coated MALDI-ToF Sample Plate for Peptide Analysis.

In this report, we describe the development and testing of a new coated plate which improves the sensitivity and accuracy in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF-MS). The coated plate was covered with a thin layer of hydrophobic silicon dioxide, which enabled sample enrichment due to the water repellent nature of the silicon dioxide surface. Sensitivity and required laser strengths were tested using peptide standards, with the results that these coated plates required lower laser power and showed increased sensitivity than that of common plates. Accuracy was tested using bacteria, saliva, and serum samples. The coated plates showed significantly increased degrees of accuracy through their capacity to reduce mass shift. The importance and necessity of accuracy analysis in the assessment of new sample plates, which is rarely described in other papers, is also discussed.

Tough pNAGA hydrogel hybridized porcine pericardium for the pre-mounted TAVI valve with improved anti-tearing properties and hemocompatibility.

The rate of adoption of transcatheter aortic valve implantation (TAVI) is increasing rapidly, due to the procedure being less invasive. However, TAVI still faces problems relating to durability, the potential incidence of thrombosis, and the inconvenience of storage in glutaraldehyde (Glut) solution. In this work, a tough hydrogel poly(N-acryloyl glycinamide) (pNAGA) is hybridized with Glut-crosslinked porcine pericardium (Glut-PP) via in situ polymerization and glycerolization, so as to obtain dry leafet material for the fabrication of a pre-mounted bioprosthetic heart valve (BHV). The tensile strength, anti-shearing, and anti-tearing properties of the valve are significantly improved by the process of hydrogel hybridization. Following a period of dry-state compression as a simulation for the crimping process of pre-mounted TAV, pNAGA/Glut-PP showed full recovery without structural damage when fully rehydrated. The introduction of pNAGA also improved the blood compatibility of the tissue, with less clot formation and fewer blood cells adhering to the surface of pNAGA/Glut-PP than is found with Glut-PP. Subcutaneous implantation in rats showed that pNAGA/Glut-PP induced a decreased inflammatory response compared with Glut-PP. These results indicate that the strategy for hybridization with hydrogel could be a potential method for preparing pre-mounted TAVs with an improved performance.