Ionophore-Based Potassium Selective Fluorescent Organosilica Nano-Optodes Containing Covalently Attached Solvatochromic Dyes

Fluorescent nanoprobes containing ionophores and solvatochromic dyes (SDs) were previously reported as an alternative to chromoionophore-based nano-optodes. However, the small-molecular SDs are prone to leakage and sequestration in complex samples. Here, we chemically attached the SDs to the surface of organosilica nanospheres through copper-catalyzed Click chemistry to prevent dye leakage. The nano-optodes remained well responsive to K+ even after exposure to a large amount of cation-exchange resin, which acted as a sink of the SDs. The potassium nanoprobes exhibited a dynamic range between 1 μM to 10 mM and a good selectivity thanks to valinomycin. Preliminary sensing device based on a nylon filter paper and agarose hydrogel was demonstrated. The results indicate that the covalent anchoring of SDs on nanospheres is promising for developing ionophore-based nanoprobes.

Fabrication of Low-Fouling Surfaces on Alkyne-Functionalized Poly-(p-xylylenes) Using Click Chemistry

A facial, versatile, and universal method that breaks the substrate limits is desirable for antifouling treatment. Thin films of functional poly-p-xylylenes (PPX) that are deposited using chemical vapor deposition (CVD) provide a powerful platform for surface immobilization of molecules. In this study, we prepared an alkyne-functionalized PPX coating on which poly (sulfobetaine methacrylate-co-Az) could be conjugated via click chemistry. We found that the conjugated polymers were very stable and inhibited cell adhesion and protein adsorption effectively. The same conjugation strategy could also be applied to conjugate azide-containing poly (ethylene glycol) and poly (NIPAAm). The results indicate that our method provides a simple and robust tool for fabricating antifouling surfaces on a wide range of substrates using CVD technology of functionalized poly (p-xylylenes) for biosensor, diagnostics, immunoassay, and other biomaterial applications.

Tetradentate halogen bonding macrocyclic anion receptor inspired by the “Texas-sized” molecular box

Inspired by the tetracationic “Texas-sized” molecular box, a neutral analogue containing four iodotriazole halogen bond-promoting subunits (“Ibox”) was synthesized. This new macrocycle was prepared by means of azide-alkyne click chemistry....

Bedside formulation of a personalized multi-neoantigen vaccine against mammary carcinoma

BackgroundHarnessing the immune system to purposely recognize and destroy tumors represents a significant breakthrough in clinical oncology. Non-synonymous mutations (neoantigenic peptides) were identified as powerful cancer targets. This knowledge can be exploited for further improvements of active immunotherapies, including cancer vaccines, as T cells specific for neoantigens are not attenuated by immune tolerance mechanism and do not harm healthy tissues. The current study aimed at developing an optimized multitarget vaccine using short or long neoantigenic peptides utilizing virus-like particles (VLPs) as an efficient vaccine platform.MethodsMutations of murine mammary carcinoma cells were identified by integrating mass spectrometry-based immunopeptidomics and whole exome sequencing. Neoantigenic peptides were synthesized and covalently linked to virus-like nanoparticles using a Cu-free click chemistry method for easy preparation of vaccines against mouse mammary carcinoma.ResultsAs compared with short peptides, vaccination with long peptides was superior in the generation of neoantigen-specific CD4+ and CD8+ T cells, which readily produced interferon gamma (IFN-γ) and tumor-necrosis factor α (TNF-α). The resulting anti-tumor effect was associated with favorable immune re-polarization in the tumor microenvironment through reduction of myeloid-derived suppressor cells. Vaccination with long neoantigenic peptides also decreased post-surgical tumor recurrence and metastases, and prolonged mouse survival, despite the tumor’s low mutational burden.ConclusionIntegrating mass spectrometry-based immunopeptidomics and whole exome sequencing is an efficient approach for identifying neoantigenic peptides. Our multitarget VLP-based vaccine shows a promising anti-tumor effect in an aggressive murine mammary carcinoma model. Future clinical application using this strategy is readily feasible and practical, as click chemistry coupling of personalized synthetic peptides to the nanoparticles can be done at the bedside directly before injection.

Bio-click chemistry: a bridge between biocatalysis and click chemistry

This review summarizes chemo/biocatalytic syntheses that combine the highly efficient click chemistry reactions with the advantages of biocatalysis. The concept of bio-click chemistry and its implications are introduced in this review.