A Nonconjugated Zwitterionic Polymer: Cathode Interfacial Layer Comparable with PFN for Narrow-Bandgap Polymer Solar Cells.

A nonconjugated, alcohol-soluble zwitterionic polymer, poly(sulfobetaine methacrylate) (denoted by PSBMA), is employed as cathode interfacial layer (CIL) in polymer solar cells (PSCs) based on PTB7-Th:PC71 BM. Compared with the control device without CIL, PSCs with PSBMA CILs show significant enhancement on the resulting performance, and the highest power conversion efficiency (PCE) of 8.27% is achieved. Under parallel conditions, PSCs with PSBMA as CIL show comparable performance than those with widely used poly[(9,9-bis(30-(N,N-dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-ioctylfluorene)] as CIL. The polar groups of PSBMA not only provide a solvent orthogonal solubility in the process of preparation of the devices but also lead to interfacial dipole to the electrode, which promises a better energy level alignment. In addition, PSBMA-based devices show better abilities of hole blocking. These results indicate that the zwitterionic polymer PSBMA should be a promising CIL in PSC-based narrow-bandgap polymers.

Construction of novel antiplatelet modified polyethersulfone membrane and study into its blood compatibility.

Blood purification therapy is widely used in patients with renal insufficiency and severe infections, where membrane-associated thrombosis is a side effect. How to improve the hemocompatibility of dialysis membranes and reduce thrombosis is a focus of current research, in which platelets play a key role. However, few dialysis membranes that directly inhibit platelets have been developed to date. In this study, a polyethersulfone (PES) membrane was modified with ticagrelor, a platelet P2Y12 receptor inhibitor, and detailed characterization was performed. The ticagrelor modified PES membrane (TMPES) showed good hydrophilicity and anti-protein adsorption and significantly inhibited platelet adhesion, aggregation, and activation, which demonstrated good antithrombotic properties. In addition, the membrane had excellent red blood cell (RBC) compatibility, anticoagulant, and antiinflammatory effects, which demonstrated superior biosafety in cell and animal experiments. Therefore, the TMPES dialysis membrane could have potential in clinical applications.

Vorapaxar-modified polysulfone membrane with high hemocompatibility inhibits thrombosis.

Hemodialysis therapy is intended for patients suffering from renal insufficiency, pancreatitis, and other serious diseases. Platelets are an important active ingredient in the thrombosis induced by hemodialysis membranes. So far, there are few studies of hemodialysis membranes focusing on the effects of protease-activated receptor 1 (PAR1) activation on the platelet membrane. Among various antithrombotic agents, vorapaxar is a novel PAR1 inhibitor with high efficacy. In this study, we constructed a vorapaxar-modified polysulfone (VMPSf) membrane using immersion-precipitation phase transformation methods and characterized the microstructure in terms of hydrophilicity and mechanical properties. The water contact angle of the VMPSf membrane was 22.45% lower than that of the PSf membrane. A focused determination of platelet morphology was obtained using scanning electron microscopy. Meanwhile, we evaluated the effects of a VMPSf membrane on platelet adhesion. We observed that the VMPSf membrane could reduce the number of adhered platelets without altering their spherical or elliptical shape. The PAR1 levels in VMPSf membranes were 7.4 MFI lower than those in PSf membranes, suggesting that this modified membrane can effectively inhibit platelet activation. Activated partial thromboplastin time (APTT, 5.3 s extension) and thrombin time (TT, 2.1 s extension) reflect good anticoagulant properties. Recalcification time (80.6 s extension) and fibrinogen adsorption (9.9 µg/cm2 reduction) were related to antithrombotic properties. To determine the biosafety of VMPSf membranes, we investigated antianaphylactic and anti-inflammatory properties in vitro and acute toxicity in vivo, it was obvious that C3a and C5a had decreased to 9.6 and 0.8 ng/mL, respectively. The results indicated that the VMPSf membrane has potential for clinical application.

Responsive Carbonized Polymer Dots for Optical Super-resolution and Fluorescence Lifetime Imaging of Nucleic Acids in Living Cells.

The rapid development of advanced optical imaging methods including stimulated emission depletion (STED) and fluorescence lifetime imaging microscopy (FLIM) has provided powerful tools for real-time observation of submicrometer biotargets to achieve unprecedented spatial and temporal resolutions. However, the practical imaging qualities are often limited by the performance of fluorescent probes, leading to unsatisfactory results. In particular, long-term imaging of nucleic acids in living cells with STED and FLIM remained desirable yet challenging due to the lack of competent probes combining targeting specificity, biocompatibility, low power requirement, and photostability. In this work, we rationally designed and synthesized a nanosized carbonized polymer dot (CPD) material, CPDs-3, with highly efficient and photostable emission for the super-resolution and fluorescence lifetime imaging of nucleic acids in living cells. The as-fabricated nanoprobe showed responsive emission properties upon binding with nucleic acids, providing an excellent signal-to-noise ratio in both spatial and temporal dimensions. Moreover, the characteristic saturation intensity value of CPDs-3 was as low as 0.68 mW (0.23 MW/cm2), allowing the direct observation of chromatin structures with subdiffraction resolution (90 nm) at very low excitation (<1 µW) and depletion power (<5 mW). Owing to its low toxicity, high photonic efficiency, and outstanding photostability, CPDs-3 was capable of performing long-term imaging both with STED and FLIM setups, demonstrating great potential for the dynamic study of nucleic acid functionalities in the long run.

Thin platelet-like COF nanocomposites for blood brain barrier transport and inhibition of brain metastasis from renal cancer.

Effective treatment of brain metastases is hindered by the blood-brain barrier (BBB) and the rapid development of resistance to drug therapy. Moreover, the clinical application of general formulations is hampered by biological barriers and biological elimination. To tackle this challenge, we report a feasible approach for the assembly of polymer-covalent organic framework (COF) nanocomposites into 150 nm thin platelets as a drug delivery vehicle for enhanced retention in brain tumours. Using intravital imaging, we demonstrate that these polymer-COF nanocomposites are able to traverse the BBB in mice and achieve direct tumour accumulation in intracranial orthotopic models of brain metastasis from renal cancer (BMRC). These nanocomposites can target brain tumour cells and respond to tumour microenvironmental characteristics, including acidic and redox conditions. Intracranial tumour acidity triggers the breakdown of the nanoassemblies to polymer-COF nanocomposites due to the presence of borate bonds. Furthermore, in vivo studies on the nanocomposites showed enhanced brain tumour-targeting efficiency and therapeutic effects compared to those of free-drug dosing. Mice treated with drug-loaded polymer-COF nanocomposites also show protection from systemic drug toxicity and improved survival, demonstrating the preclinical potential of this nanoscale platform to deliver novel combination therapies to BMRC and other central nervous system (CNS) tumours.

Water-dispersible PEG-curcumin/amine-functionalized covalent organic framework nanocomposites as smart carriers for in vivo drug delivery.

Covalent organic frameworks (COFs) as drug-delivery carriers have been mostly evaluated in vitro due to the lack of COFs nanocarriers that are suitable for in vivo studies. Here we develop a series of water-dispersible polymer-COF nanocomposites through the assembly of polyethylene-glycol-modified monofunctional curcumin derivatives (PEG-CCM) and amine-functionalized COFs (APTES-COF-1) for in vitro and in vivo drug delivery. The real-time fluorescence response shows efficient tracking of the COF-based materials upon cellular uptake and anticancer drug (doxorubicin (DOX)) release. Notably, in vitro and in vivo studies demonstrate that PEG-CCM@APTES-COF-1 is a smart carrier for drug delivery with superior stability, intrinsic biodegradability, high DOX loading capacity, strong and stable fluorescence, prolonged circulation time and improved drug accumulation in tumors. More intriguingly, PEG350-CCM@APTES-COF-1 presents an effective targeting strategy for brain research. We envisage that PEG-CCM@APTES-COF-1 nanocomposites represent a great promise toward the development of a multifunctional platform for cancer-targeted in vivo drug delivery.

Single-stranded γPNAs for in vivo site-specific genome editing via Watson-Crick recognition.

Triplex-forming peptide nucleic acids (PNAs) facilitate gene editing by stimulating recombination of donor DNAs within genomic DNA via site-specific formation of altered helical structures that further stimulate DNA repair. However, PNAs designed for triplex formation are sequence restricted to homopurine sites. Herein we describe a novel strategy where next generation single-stranded gamma PNAs (γPNAs) containing miniPEG substitutions at the gamma position can target genomic DNA in mouse bone marrow at mixed-sequence sites to induce targeted gene editing. In addition to enhanced binding, γPNAs confer increased solubility and improved formulation into poly(lactic-co-glycolic acid) (PLGA) nanoparticles for efficient intracellular delivery. Single-stranded γPNAs induce targeted gene editing at frequencies of 0.8% in mouse bone marrow cells treated ex vivo and 0.1% in vivo via IV injection, without detectable toxicity. These results suggest that γPNAs may provide a new tool for induced gene editing based on Watson-Crick recognition without sequence restriction.

[Reconstruction of tissue defects with forehead island flap in gerontal patients after oral cancer surgery].

PURPOSE: To investigate the role of repairing oral tissue defects with forehead island flap after oral cancer surgery in gerontal patients. METHODS: Reconstruction of oral tissue defects with forehead island flap was performed simultaneously after radical excision in 13 gerontal patients suffering from oral cancers. Eight forehead flaps were introduced into oral cavity under zygomatic arch, 5 were around the zygomatic arch into the oral cavity. The flaps were used to repair oral tissue defects, such as the cheek, tongue, retromolar region and floor of mouth. RESULTS: All the flaps survived well. The defect of forehead donor region was repaired with free skin graft. The color of skin graft was close to normal skin 1 year after operation, the forehead deformity was not obvious, but the skin mobility was poor. No tumor recurrence and metastasis occurred during 6 months to 2 years of follow-up. CONCLUSION: Reconstruction of oral cavity with forehead island flap is suitable for gerontal patients with oral cancer.