Thrombolysis with tissue plasminogen activator (tPA) provides the most common therapy for ischemic stroke onset within the past 4.5 h. However, enhanced neutrophil infiltration and secondary blood-brain barrier injury caused by tPA administration have limited its therapeutic application, and tPA treatment is often accompanied by hemorrhagic transformation. To overcome the limitations of thrombolysis by tPA, maximize the therapeutic efficacy, and improve the safety, herein, we report a cryo-shocked platelet-based cell-hitchhiking drug delivery system, which consists of cryo-shocked platelet (CsPLT) and reactive oxygen species (ROS)-responsive liposomes loaded with thrombolytic tPA and anti-inflammation drug aspirin (ASA). CsPLT and liposomes were facilely conjugated via host–guest interactions. Under the guidance of CsPLT, it selectively accumulated in the thrombus site and quickly released the therapeutic payloads in response to the high ROS. tPA subsequently exhibited localized thrombolytic activity to suppress the expansion of thrombus, while ASA assisted in the inactivation of reactive astrogliosis, microglial/macrophage, and obstruction of neutrophil infiltration. This cryo-shocked platelet-hitchhiking tPA/ASA delivery system not only improves the thrombus-targeting efficiency of the two drugs for highly localized thrombolytic effects and anti-inflammation actions and platelets inactivation but also provides insights to the development of targeted drug delivery systems for thromboembolic disease treatment.
Effective molecularly imprinted membranes(MIMs) were developed as an efficient adsorbent for the selective removal of p -hydroxybenzoic acid( p -HB) from acetylsalicylic acid(ASA, aspirin). The MIMs were grafted successfully from poly(vinylidene fluoride) microfiltration membranes via reversible addition-fragmentation chain transfer(RAFT) polymerization. The graft copolymerization of acrylic acid(AA) in the presence of template p -hydroxybenzoic acid led to molecularly imprinted polymer(MIP) film coated membranes. The obtained MIMs were characterized by scanning electron microscopy(SEM), Fourier transform infrared spectrophotometer(FTIR) and Raman spectra, and batch mode adsorption studies were carried out to investigate the specific adsorption equilibrium, kinetics and selective recognition properties of different MIMs. The kinetic properties of the MIMs could be well described by the pseudo-second-order rate equation. Selective permeation experiments were performed to evaluate the permeation selectivity of the p -HB imprinted membranes. The observed performances of the MIMs are applicable to the further purification of aspirin.
A novel electrochemical immunoassay platform for multi-signal amplification has been constructed and applied to the simultaneous detection of three tumor markers (TMs). The platform was successfully developed by polyethyleneimine (PEI)-polydopamine (PDA)/reduced graphene oxide (rGO) nanocomposites. PDA/rGO as the substrates can simultaneously load with detection antibodies (Ab 2 ) and large amounts of PEI, which PEI were further used to immobilize different signal labels. Three TMs of carcinoembryonic antigen (CEA), prostate specific antigen (PSA) and alpha fetoprotein (AFP) were employed as potential factors. Ferrocenecarboxylic acid (Fc), anthraquinone-2-carboxylic acid (Aq) and acetylsalicylic acid (ASA) were employed as distinguishable signal labels. Electrochemical responses of designed sandwich-type immunosensor were successfully investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The multiplexed immunoassay displayed excellent linear response in the range of 0.102 pg/mL–112 ng/mL for CEA and PSA, 0.117 pg/mL–117 ng/mL for AFP. The detection limit of three TMs were 91 fg/mL, 101 fg/mL and 83 fg/mL for CEA, PSA and AFP, respectively. Moreover, this electrochemical immunoassay platform exhibited excellent reproducibility, sensitivity and selectivity for the simultaneous detection of multiple biomarkers.
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