Folic acid-conjugated liposomal vincristine for multidrug resistant cancer therapy

We encapsulated vincristine into folic acid-conjugated PEGylated liposomes to improve the anti-tumor efficacy on multidrug resistant cancers.It was observed that the drug delivery system we constructed exhibited maximum cytotoxicity on KBv200 cells(multidrug resistant variant)compared with any other formulations.The semi-quantitative analysis of region of interest revealed that there was a great increase in area under curve(AUC)of a near-infrared fluorescein in solid tumors due to folic acid-mediated accumulation.Folic acid-conjugated PEGylated liposomes showed a significant tumor growth inhibiting effect in vitro and in vivo.TUNEL assay revealed that folic acid-conjugated PEGylated liposomes could induce cell apoptosis much more greatly than others.This study demonstrated that it had potential application prospective for the treatment of multidrug resistant cancer.

Breaking or following the membrane-targeting mechanism:Exploring the antibacterial mechanism of host defense peptide mimicking poly(2-oxazoline)s

Peptides exert important biological functions but their application is hindered by their susceptibility to proteolysis and poor stability in vivo.Thus,functional peptide mimics have drawn a great deal of attention to address this challenge.Poly(2-oxazoline)s,a class of biocompatible and proteolysis-resistant polymer,can work as host defense peptide mimics without following the general membrane-targeting mechanism as shown in our previous work.This observation encouraged us to figure out if poly(2-oxazoline)s are special and break the general membrane-targeting mechanism of host defense peptides and their mimics.In this study,we aimed at the connection between structure and antibacterial mechanism of poly(2-oxazoline)s.A new γ-aminobutyric acid(GABA)-pendent poly(2-oxazoline)was synthesized and investigated to compare with glycine-pendent poly(2-oxazoline)in our previous study,with the former polymer has two extra CH2 groups in the sidechain to increase the hydrophobicity and amphiphilicity.Membrane depolarization assay suggested that incorporating two more CH2 groups into the sidechain of poly(2-oxazoline)resulted in a mechanism switch from DNA-targeting to membrane-targeting,which was supported by the slow time-kill kinetics and slightly distorted and sunken membrane morphology.Besides,GABA-pendent poly(2-oxazoline)showed potent activity against methicillin-resistant S.aureus and low hemolysis on human red blood cells.Moreover,repeated use of the antimicrobial poly(2-oxazoline)did not stimulate bacteria to obtain resistance,which was an obvious advantage of membrane-targeting antimicrobial agents.

A ROS-Responsive Aspirin Polymeric Prodrug for Modulation of Tumor Microenvironment and Cancer Immunotherapy

Tumor-promoting inflammation is accompanied by cancer initiation,progression,and metastasis.Cyclooxygenase-2(COX-2)and its downstream product,prostaglandin E2(PGE2),play critical roles in tumor-promoting inflammation.Several studies have revealed the potential of COX-2 inhibition in improving cancer response to chemotherapy,as well as immunotherapy.Aspirin,a nonsteroidal anti-inflammatory drug,has been reported as a COX-2 inhibitor.However,as a small molecule drug with a carboxyl group,there is still the lack of effective methods of preparing polymer–aspirin conjugates with tumor stimuli-responsive release properties.Herein,we synthesized a reactive oxygen species(ROS)-responsive aspirin polymeric prodrug(P3C-Asp)via Passerini three-component reaction between aspirin,4-formylbenzeneboronic acid pinacol ester,and 5-isocyanopent-1-yne,followed by copper(I)-catalyzed alkyne-azide cycloaddition“click”reaction of the aspirin prodrug with dextran(DEX).The P3C-Asp could release aspirin and salicylic acid in response to tumor-specific stimuli.In the murine colorectal cancer model,P3C-Asp suppressed tumor growth effectively without significant side effects and eradicated tumors when combined with the immune checkpoint inhibitor,anti-PD-1 antibody(aPD-1).Further analysis revealed that the suppression was attributable to changes in the immune microenvironment,including reduced PGE2 content,as well as increased infiltration of CD8+T cells and M1 macrophages.The results mentioned above proved that targeting COX-2 pathway with a proper polymeric prodrug might be a useful strategy for cancer immunotherapy.

Nitric oxide-generating self-assembling peptide hydrogel coating for enhancing hemocompatibility of blood-contacting devices

Thrombosis is the major stumbling block to the clinical application of blood-contacting devices.Herein,a quick and easy surface engineering strategy of hydrogel coating with the therapeutic gas nitric oxide(NO)generation was reported to realize up-regulation of cyclic guanosine monophosphate(c GMP)and improve hemocompatibility for diverse metal materials.We first introduce the active centre selenocysteine of glutathione peroxidase(GPx)to the self-assembling peptide(RADA)4,obtaining a functionalized hydrogel.Then the hydrogel is directly coated on the 316L stainless steel(SS)for catalytically generating NO from endogenous s-nitrosothiols(RSNO).The generated NO endows the coated surface with regulation of platelet behavior and reduction of plasmatic coagulation activation and complement system activation,hence improving antithrombotic ability in vitro and ex vivo.Overall,our NO-generating hydrogel coating surface engineering strategy provides a novel solution to remove the obstacle about thrombosis of blood-contacting devices in clinic.

Correction to “Folic acid-conjugated liposomal vincristine for multidrug resistant cancer therapy”

In the original version of this article on p 122, two inappropriate images were placed in B and C of Fig. 1, which didn’t represent the group of FA-PEG-LS and PEG-LS/VCR. In the revised graphic provided below, the appropriate images are used.These corrections do not change the results and conclusions of this work.

Solution-Processable Platinum-Acetylide-based Small Molecular Bulk Heterojunction Solar Cells

Two new solution-processable A＇-D-≡-Pt（PEt3）2-≡-D-A＇ structured molecules, namely, CNPT and DRPT, were synthesized and characterized for photovoltaic applications. Their optoelectronic properties were investigated by UV-vis absorption and cyclic voltammograms. Grazing-incidence wide-angle X-ray scattering and resonant soft X-ray scattering studies revealed that the DIO additive could enhance the crystallization of CNPT and reduce the size of phase separation of CNPT：PC71BM blends, while the addition of DIO showed little influence on the crystal- lization and morphology of the DRPT：PC71BM blends. Processing with the DIO additive, CNPT：PC71BM based solar cells showed a best power conversion efficiency of 1.4%, with a Jsc of 4.14 mA·cm^-2, a Voc of 0.75 V, and a fill factor of 45.4%.

p-Hydroxybenzoic acid (p-HA) modified polymeric micelles for brain-targeted docetaxel delivery

Chemotherapies for brain diseases have been hampered due to the inability of transport of drug across the blood-brain barrier (BBB). In order to overcome the barrier, p-hydroxybenzoic acid (p-HA), a small molecule of benzamide analogue, was used as a ligand for brain-targeted drug delivery. The p-HA was conjugated to PEG-DSPE to form p-HA-PEG-DSPE. Docetaxel-loaded polymeric micelles were prepared by a thin-film hydration method using methoxy-poly(ethylene glycol)-distearoylphosphatidyl- ethanolamine (mPEG 2000 -DSPE) as a carrier and the p-HA-PEG-DSPE as a brain targeted material. The prepared micelles showed spherical with a mean diameter of (18±3) nm. Encapsulation efficiency and drug loading were (83.49±1.3)%, (7.7±1.2)% for un- modified micelles and (80.65±1.6)%, (7.47±1.8)% for p-HA-modified micelles, respectively. In vitro cellular uptake experiments showed that the p-HA-modified micelles increased BCECs cellular uptake by 1.2 times compared to the unmodified micelles. Ex vivo near-infrared fluorescence imaging showed that brain uptake of the p-HA-modified micelles was 1.3-1.8 times higher than that of the unmodified micelles. In vitro cytotoxicity assay against glioblastoma cell U87 MG showed that inhibition rate of the p-HA-modified micelles increased by 1.2 times compared to that of the unmodified micelles and 1.7 times compared to that of DTX. Survival time of nude mice bearing intracranial glioblastoma showed that the lifetime of saline group, Taxotere group, mPEG-DSPE/DTX micelles group and p-HA-PEG-DSPE/DTX micelles group was 22, 27, 32 and 45.8 d, representively, which indicated that anti-glioblastoma activity of DTX could be significantly enhanced by the p-HA-modified polymeric micelles. These results demonstrated that the p-HA-modified micelles could be a promising brain-targeted drug delivery system for hydrophobic drugs against glioblastoma.

一种具有优良自愈合性和再加工性的富氟聚酚氨酯弹性体及其在可穿戴电子领域的应用

具有共价适应性网络的聚氨酯弹性体(PU-CANs)因其具有再加工性、自适应性和自愈合性而引起了人们的广泛关注.然而氨基甲酸酯的键能通常较高,在低温下实现其优异的动态性能仍然是一项艰巨的挑战.针对以上问题,基于动态性能可调范围广的酚氨基甲酸酯键,我们成功设计并制备了一种具有CANs的氟化聚酚氨酯弹性体(FPPU),系统地研究了氟原子对弹性体力学性能、热学性能、可再加工性、自愈性、表面自由能及疏水性的影响.和非氟化的聚酚氨酯弹性体(APPU)相比,FPPU表现出缺口不敏感性、自愈合效率高(98%)、动态解离温度低(60℃)、优异的可再加工性和低表面能(62 MJ m^(-2)).基于上述优点,FPPU被选为弹性基底,用于组装自供电的摩擦纳米发电机(TENG).该TENG具有优良的电输出性能,开路电压的峰值为103 V,短路电流的峰值为4.7μA,短路电荷的峰值为43 nC.此外,TENG还具有良好的自清洁性和再加工性.更进一步地,基于FPPU构建了面向柔性电子器件的可拉伸和自愈合复合导体.