Magic™ Anti-TAT monoclonal antibody, clone N92779

We report the glutathione-triggered release of an anticancer drug from vesicles constructed with peptide amphiphiles (PAs) containing a cell-penetrating TAT peptide synthesized by varying the position and number of disulfide-linkages in the PAs. PAs 1 and 2, based on random-coil structures that enable large amounts of drug loading, showed different self-assembled aggregates. These included vesicles and two-dimensional sheets as functions of the cysteine (C) position in the PA, despite the use of the same chemical building blocks. However, the formation of C-C disulfide-bridges between neighboring PAs by sonication in polar-aprotic solvent, dimethylformamide led to morphological changes into the vesicles. Interestingly, the PA vesicles demonstrated markedly different drug loading capacities and efficiencies as functions of the disulfide position during assembly. Increases in the number of disulfide formations between PAs (1-1) allowed the vesicular drug transporter to exhibit sustained anticancer-drug release to specific tumors. As all vesicles reported in this study exhibited a superior ability to deliver anticancer drugs to certain cancer cells alone, this research, which provides a biocompatible peptide design for the synthesis of efficient drug-delivery vehicles, can serve as a solid foundation for further nanocarrier developments for biomedical applications.

The combination of atrial fibrillation (AF) and acute coronary syndrome (ACS) is a complex situation in which a three-dimensional risk-cardioembolic, coronary, and hemorrhagic-has to be carefully managed. Triple antithrombotic therapy (TAT) is burdened with a high risk of serious bleeding, while dual antithrombotic therapy with an anticoagulant (DAT) likely provides only suboptimal coronary protection early after stent implantation. Moreover, TAT precludes the advantages provided by the use of the latest and more potent P2Y(12)inhibitors in ACS patients. Here, we aimed to simulate and compare the expected coronary, cardioembolic, and hemorrhagic outcomes offered by DAT, TAT, or modern dual antiplatelet therapy (DAPT) with aspirin plus one of the latest P2Y(12)inhibitors in AF patients early after an ACS. The comparison of numbers needed to treat to prevent major adverse events with the various antithrombotic regimens suggests that AF-ACS patients at high ischemic and hemorrhagic risk and at moderately low embolic risk (CHA(2)DS(2)VASc score 2-4) might safely withhold anticoagulation after revascularization for one month taking advantage of a modern DAPT, with a favorable risk-to-benefit ratio. In conclusion, this strategy, not sufficiently addressed in recent European and North American guidelines or consensus documents, adds to the spectrum of treatment options in these difficult patients; it might be the best choice in a substantial number of patients; and should be prospectively tested in a randomized controlled trial.