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Despite promising results in malaria-naïve individuals, whole sporozoite (SPZ) vaccine efficacy in malaria-endemic settings has been suboptimal. Vaccine hypo-responsiveness due to previous malaria exposure has been posited as responsible, indicating the need for SPZ vaccines of increased immunogenicity. To this end, we here demonstrate a proof-of-concept for altering SPZ immunogenicity, where supramolecular chemistry enables chemical augmentation of the parasite surface with a TLR7 agonist-based adjuvant (SPZ-SAS(CL307)). In vitro, SPZ-SAS(CL307) remained well recognized by immune cells and induced a 35-fold increase in the production of pro-inflammatory IL-6 (p < 0.001). More promisingly, immunization of mice with SPZ-SAS(CL307) yielded improved SPZ-specific IFN-γ production in liver-derived NK cells (percentage IFN-γ+ cells 11.1 ± 1.8 vs. 9.4 ± 1.5%, p < 0.05), CD4+ T cells (4.7 ± 4.3 vs. 1.8 ± 0.7%, p < 0.05) and CD8+ T cells (3.6 ± 1.4 vs. 2.5 ± 0.9%, p < 0.05). These findings demonstrate the potential of using chemical augmentation strategies to enhance the immunogenicity of SPZ-based malaria vaccines.

Background: Surgically induced nerve damage is a common but debilitating side effect. By developing tracers that specifically target the most abundant protein in peripheral myelin, namely myelin protein zero (P0), we intend to support fluorescence-guided nerve-sparing surgery. To that end, we aimed to develop a dimeric tracer that shows a superior affinity for P0. Methods: Following truncation of homotypic P0 protein-based peptide sequences and fluorescence labeling, the lead compound Cy5-P0101–125 was selected. Using a bifunctional fluorescent dye, the dimeric Cy5-(P0101–125)2 was created. Assessment of the performance of the mono- and bi-labeled compounds was based on (photo)physical evaluation. This was followed by in vitro assessment in P0 expressing Schwannoma cell cultures by means of fluorescence confocal imaging (specificity, location of binding) and flow cytometry (binding affinity; KD). Results: Dimerization resulted in a 1.5-fold increase in affinity compared to the mono-labeled counterpart (70.3 +/− 10.0 nM vs. 104.9 +/− 16.7 nM; p = 0.003) which resulted in a 4-fold increase in staining efficiency in P0 expressing Schwannoma cells. Presence of two targeting vectors also improves a pharmacokinetics of labeled compounds by lowering serum binding and optical stability by preventing dye stacking. Conclusions: Dimerization of the nerve-targeting peptide P0101–125 proves a valid strategy to improve P0 targeting.

The Lycurgus cup is an ancient glass artefact that shows dichroism as it looks green when a white light is reflected on it and a red colouring appears when a white light is transmitted through it. This peculiar dichroic effect is due to silver and gold nanoparticles present in the glass. In this research we show the synthesis of dichroic silver nanoparticles and their embedding in a 3D printable nanocomposite. The addition of gold nanoparticles to the silver nanoparticle composite, gave a 3D printable nanocomposite with the same dichroism effect of the Lycurgus cup.

Background: Nanotechnology, even if unknowingly, has been used for millennia. The occurrence of shiny colors in pottery and glass made hundreds and thousand of years ago is due to the presence of nanoparticles in the fabrication of such ornaments. In the last decade, 3D printing has revolutionized fabrication and manufacturing processes, making it easier to produce, in a simple and fast way, 3D objects.Results: In this paper we show how to fabricate a 3D-printable nanocomposite composed of dichroic gold nanoparticles and a 3D-printable polymer. The minute amount of gold nanoparticles used for obtaining the dichroic effect does not influence the mechanical properties of the polymer nor its printability. Thus, the nanocomposite can be easily 3D-printed using a standard 3D printer and shows a purple color in transmission and a brownish color in reflection.Conclusion: This methodology can be used not only by artists, but also for studying the optical properties of nanoparticles or, for example, for the 3D fabrication of optical filters.

UnlabelledScreening of biomarker expression levels in tumor biopsy samples not only provides an assessment of prognostic and predictive factors, but may also be used for selection of biomarker-specific imaging strategies. To assess the feasibility of using a biopsy specimen for a personalized selection of an imaging agent, the chemokine receptor 4 (CXCR4) was used as a reference biomarker.MethodsA hybrid CXCR4 targeting peptide (MSAP-Ac-TZ14011) containing a fluorescent dye and a chelate for radioactive labeling was used to directly compare initial flow cytometry-based target validation in fresh tumor tissue to in vivo single photon emission computed tomography (SPECT) imaging and in vivo and ex vivo fluorescence imaging.ResultsFlow cytometric analysis of mouse tumor derived cell suspensions enabled discrimination between 4T1 control tumor lesions (with low levels of CXCR4 expression) and CXCR4 positive early, intermediate and late stage MIN-O lesions based on their CXCR4 expression levels; CXCR4(basal), CXCR4(+) and CXCR4(++) cell populations could be accurately discriminated. Mean fluorescent intensity ratios between expression in MIN-O and 4T1 tissue found with flow cytometry were comparable to ratios obtained with in vivo SPECT/CT and fluorescence imaging, ex vivo fluorescence evaluation and standard immunohistochemistry.ConclusionThe hybrid nature of a targeting imaging agent like MSAP-Ac-TZ14011 enables integration of target selection, in vivo imaging and ex vivo validation using a single agent. The use of biopsy tissue for biomarker screening can readily be expanded to other targeting hybrid imaging agents and can possibly help increase the clinical applicability of tumor-specific imaging approaches.