Ester, amide, and directly linked composites of squalene and cationic diaza [4]helicenes 1 are readily prepared. These lipid‐dye constructs 2, 3, and 4 give in aqueous media monodispersed spherical nanoassemblies around 100–130 nm in diameter with excellent stability for several months. Racemic and enantiopure nanoassemblies of compound 2 are fully characterized, including by transmission electron microscope and cryogenic transmission electron microscope imaging that did not reveal higher order supramolecular structures. Investigations of their (chir)optical properties show red absorption maxima ≈600 nm and red fluorescence spanning up to the near‐infrared region, with average Stokes shifts of 1350–1550 cm−1. Live‐cell imaging by confocal microscopy reveals rapid internalization on the minute time scale and organelle‐specific accumulation. Colocalization with MitoTracker in several cancer cell lines demonstrates a specific staining of mitochondria by the [4]helicene–squalene nanoassemblies. To our knowledge, it is the first report of a subcellular targeting by squalene‐based nanoassemblies.

Aims/hypothesisNon-invasive imaging of beta cells is a much-needed development but is one that faces significant biological and technological hurdles. A relevant imaging method should at least allow for an evaluation over time of the mass of beta cells under physiological and pathological conditions, and for an assessment of novel therapies. We, therefore, investigated the ability of a new MRI probe to repeatedly measure the loss of beta cells in a rodent model.MethodsWe developed an innovative nanoparticle probe that targets the glucagon-like peptide 1 receptor, and can be used for both fluorescence imaging and MRI. Using fluorescence, we characterised the specificity and biodistribution of the probe. Using 1.5T MRI, we longitudinally imaged the changes in insulin content in male and female mice of the RIP-DTr strain, which mimic the changes expected in type 1 and type 2 diabetes, respectively.ResultsWe showed that this probe selectively labelled beta cells in situ, imaged in vivo native pancreatic islets and evaluated their loss after diphtheria toxin administration, in a model of graded beta cell deletion. Thus, using clinical MRI, the probe quantitatively differentiates, in the same mouse strain, between female animals featuring a 50% loss of beta cells and the males featuring an almost complete loss of beta cells.Conclusions/interpretationThe approach addresses several of the hurdles that have so far limited the non-invasive imaging of beta cells, including the potential to repeatedly monitor the very same animals using clinically available equipment, and to differentiate graded losses of beta cells.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-014-3442-2) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

5-aminolevulinic acid (5-ALA) has been at the forefront of small molecule based fluorescence-guided tumor resection and photodynamic therapy. 5-ALA and two of its esters received marketing authorization but suffer from several major limitations, namely low stability and poor pharmacokinetic profile. Here, we present a new class of 5-ALA derivatives aiming at the stabilization of 5-ALA by incorporating a phosphatase sensitive group, with or without self-cleavable linker. Compared to 5-ALA hexyl ester (5-ALA-Hex), these compounds display an excellent stability under acidic, basic and physiological conditions. The activation and conversion into the 5-ALA is controlled and can be structure-tailored. The prodrugs display reduced acute toxicity compared to 5-ALA-Hex with superior dose response profiles of protoporphyrin IX synthesis and fluorescence intensity in human glioblastoma cells in vitro. Clinically relevant fluorescence kinetics in vivo shown in U87Mg glioblastoma spheroid tumor model in chick embryos provide a solid basis for their further development and translation to clinical fluorescence guided tumor resection and photodynamic therapy.