Differences in the lipid composition of prokaryotic and eukaryotic cell membranes are well understood and can be exploited to produce novel antimicrobials. However, what is less well recognised is that alteration in the phospholipid composition of the cell membrane is also one of the first phenotypic changes when a cell becomes cancerous. In addition, changes in phospholipid cell membrane composition are a known cause of drug resistance in both microbial disease and cancer. Here we present a novel, next generation series of chiral, amino acid appended supramolecular self-associating amphiphiles that suggest membrane active technologies can be used to produce novel drugs which simultaneously fight against two of the greatest global health threats facing us today, antimicrobial resistant infections and cancer diseases. We demonstrate the antimicrobial and anticancer efficacy of this membrane active amphiphile technology against susceptible and resistant Staphylococcus aureus and ovarian cancer cells. We propose a mode of action through a combination of vesicle, NMR spectroscopy and patch clamp experiments, and provide evidence that supports the potential for this class of compound to be developed as pharmaceutical agents against these diseases through in vitro drug metabolism and pharmacokinetics experiments alongside in vivo Galleria mellonella toxicity experiments.
In addition to the high sensitivity, excellent spatio-temporal resolution and powerful real-time imaging capabilities, biomedical applications impose high demands on imaging techniques. Unfortunately, conventional imaging relies on the real-time excitation and suffers from limited tissue penetration. In contrast, afterglow imaging can provide continuous and deep luminescence once the probe is excited by NIR-light, X-ray or ultrasound. As such, it can effectively avoid autofluorescence and improve the imaging sensitivity and signal-to-background ratio. Moreover, X-ray-activated afterglow probes benefit from enhanced depth of penetration, thereby allowing more effective imaging of deep-seated lesions. Such advantages have attracted the interest of researchers, which should speed up the translation of biomedical afterglow research for clinical applications. With this perspective, we provided a comparative and analytical summary of the latest advances while highlighting the most promising afterglow probes. This perspective also outlines forward-looking strategies for molecular design, working mechanisms, and clinical prospects. Moreover, future challenges and research directions are discussed. As such this perspective describes how to formulate the most promising chemical strategies through mechanistic understanding, molecular design, and functional integration, thereby maximizing the successful development of clinical probes for visualization in humans.
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