BackgroundSingle photon emission computed tomography (SPECT) is an indispensable tool in the determination of the in vivo fate of polymeric micelles. However, for this purpose, the micelles need to be radiolabeled, and almost all radiolabeling procedures published to date involve the conjugation of a chelating agent to the constituting polymer, which could actually affect their biodistribution. In this paper, we report a new facile method for radiolabeling polystyrene-b-poly(ethylene oxide) diblock copolymer micelles without the necessity of any chemical modification. Instead, we entrap the radiolabel (i.e., 111In) in the micellar core during the formation of the micelles by using tropolone as lipophilic ligand.MethodsMicelles were prepared by emulsifying a polymer solution in chloroform with a buffer containing 111In and lipophilic ligand tropolone, by stirring for about 2 h. The produced micelles were physically characterized by means of dynamic light scattering and transmission electron microscopy. The biological properties of the radiolabeled micelles were determined by means of in vivo and ex vivo evaluation. SPECT analysis was done on Balb/c-nu mice, after administration of 1 mg micelles containing 22 MBq of 111In. SPECT images were obtained over 24 h. Biodistribution of the micelles was assessed also ex vivo.ResultsThe radiolabeling method is robust and reproducible with constant radiolabeling efficiency (~30 %) even at indium concentrations that are much higher than the necessary for in vivo studies, and the radiolabel retention is more than 80 % in mouse serum at 48 h. Radiolabeled micelles having hydrodynamic radius of 97 ± 13 nm have been successfully evaluated in vivo and ex vivo in non-tumor-bearing mice, revealing significant blood circulation up to at least 24 h post injection, with low accumulation in most organs except for the liver and spleen, which are the natural organs for clearance of nanoparticles.ConclusionsAn easy and robust radiolabeling method has been developed, and its applicability is demonstrated in animal studies, showing its value for future investigation of polymeric micelles as nanocarriers in tumor-bearing mice.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0167-x) contains supplementary material, which is available to authorized users.

A large array of laterally ordered soft nanowires from worm‐like micelles on micropatterned surfaces are generated by a simple and effective method. The nanowires can easily be modified and decorated by simple physical (hydrophobic/hydrophilic) interactions, which creates new opportunities for specific chemical and biosensing applications.

In a study aimed at identifying new anti-prion compounds we screened a library of 500 Australian marine invertebrate derived extracts using a yeast-based anti-prion assay. This resulted in an extract from the subtropical sponge Lamellodysidea cf. chlorea showing potent anti-prion activity. The bioassay-guided investigation of the sponge extract led to the isolation of three new bioactive polyoxygenated steroids, lamellosterols A−C (1−3). These sterols were all isolated in low yield, and their structures elucidated by extensive NMR and MS data analysis. Lamellosterols A−C displayed potent anti-prion activity against the [PSI + ] yeast prion (EC 50 s of 12.7, 13.8, and 9.8 μM, respectively). Lamellosterol A (1) was further shown to bind to the Parkinson's disease implicated amyloid protein, α-synuclein, and to significantly inhibit its aggregation. Our findings indicate that these polyoxygenated sterol sulfates may be useful compounds to study mechanisms associated with neurodegenerative diseases.

As part of an ongoing program to identify new bioactive compounds from Irish marine bioresources, we selected the subtidal sponge Spongosorites calcicola for chemical study, as fractions of this species displayed interesting cytotoxic bioactivities and chemical profiles. The first chemical investigation of this marine species led to the discovery of two new bisindole alkaloids of the topsentin family, together with six other known indole alkaloids. Missing the usual central core featured by the representatives of these marine natural products, the new metabolites may represent key biosynthetic intermediates for other known bisindoles. These compounds were found to exhibit weak cytotoxic activity against HeLa tumour cells, suggesting a specificity towards previously screened carcinoma and leukaemia cells.

One of the major medical challenges of the twenty-first century is the treatment of incurable and fatal neurodegenerative disorders caused by misfolded prion proteins. Since the discovery of these diseases a number of studies have been conducted to identify small molecules for their treatment, however to date no curative treatment is available. These studies can be highly expensive and time consuming, but more recent experimental approaches indicate a significant application for yeast prions in these studies. We therefore used yeast prions to optimize previous high-throughput methods for the cheaper, easier and more rapid screening of natural extracts. Through this approach we aimed to identify natural yeast-prion inhibitors that could be useful in the development of novel treatment strategies for neurodegenerative disorders. We screened 500 marine invertebrate extracts from temperate waters in Australia allowing the identification of yeast-prion inhibiting extracts. Through the bioassay-driven chemical investigation of an active Suberites sponge extract, a group of bromotyrosine derivatives were identified as potent yeast-prion inhibitors. This study outlines the importance of natural products and yeast prions as a first-stage screen for the identification of new chemically diverse and bioactive compounds.

A library of 500 Australian marine invertebrate extracts was screened for anti-prion activity using a yeast-based assay, and this resulted in an extract from the ascidian Polycarpa procera showing potent activity. Purification of this extract led to the isolation of six new butenolide metabolites, the procerolides 1–4 and two related diphenylpropanones, the procerones 5 and 6, as the bioactive components. The structures of 1–6 were elucidated from the analysis of 1D/2D NMR and MS data, and their absolute configurations determined from comparison of experimental and computed ECD data. Compounds 1–6 were tested for anti-prion activity in a yeast-based assay, and 1 and 5 displayed potent bioactivity (EC50 of 23 and 29 μM, respectively) comparable to the potently active anti-prion compound guanabenz. The procerolides and procerones are the first anti-prion compounds to be reported from ascidians, indicating that ascidians may be an untapped source of new lead anti-prion compounds.

A novel and facile approach to fabricating well-organized macroscopic 2D networks of cylindrical micelles is reported, based on transfer printing and thermal welding of aligned supramolecular micelles of block copolymers. This versatile approach provides a new strategy for fabricating functional 2D superstructures with a higher level of order.

Much recent interest has arisen in investigating Streptomyces isolates derived from the marine environment in the search for new bioactive compounds, particularly those found in association with marine invertebrates, such as sponges. Among these new compounds recently identified from marine Streptomyces isolates are the octapeptidic surugamides, which have been shown to possess anticancer and antifungal activities. By employing genome mining followed by an one strain many compounds (OSMAC)-based approach, we have identified the previously unreported capability of a marine sponge-derived isolate, namely Streptomyces sp. SM17, to produce surugamide A. Phylogenomics analyses provided novel insights on the distribution and conservation of the surugamides biosynthetic gene cluster (sur BGC) and suggested a closer relatedness between marine-derived sur BGCs than their terrestrially derived counterparts. Subsequent analysis showed differential production of surugamide A when comparing the closely related marine and terrestrial isolates, namely Streptomyces sp. SM17 and Streptomyces albidoflavus J1074. SM17 produced higher levels of surugamide A than S. albidoflavus J1074 under all conditions tested, and in particular producing >13-fold higher levels when grown in YD and 3-fold higher levels in SYP-NaCl medium. In addition, surugamide A production was repressed in TSB and YD medium, suggesting that carbon catabolite repression (CCR) may influence the production of surugamides in these strains.