Herein we demonstrate that an external electric field (EEF) acts as an accessory catalyst/inhibitor for Diels-Alder (DA) reactions. When the EEF is oriented along the "reaction axis" (the coordinate of approach of the reactants in the reaction path), the barrier of the DA reactions is lowered by a significant amount, equivalent to rate enhancements by 4-6 orders of magnitude. Simply flipping the EEF direction has the opposite effect, and the EEF acts as an inhibitor. Additionally, an EEF oriented perpendicular to the "reaction axis" in the direction of the individual molecule dipoles can change the endo/exo selectivity, favouring one or the other depending on the positive/negative directions of the EEF vis-à-vis the individual molecular dipole. At some critical value of the EEF along the "reaction axis", there is a crossover to a stepwise mechanism that involves a zwitterionic intermediate. The valence bond diagram model is used to comprehend these trends and to derive a selection rule for EEF effects on chemical reactions: an EEF aligned in the direction of the electron flow between the reactants will lower the reaction barrier. It is shown that the exo/endo control by the EEF is not associated with changes in secondary orbital interactions.

Application of immune cell-based therapy in routine clinical practice is challenging due to the poorly understood mechanisms underlying success or failure of treatment. Development of accurate and quantitative imaging techniques for noninvasive cell tracking can provide essential knowledge for elucidating these mechanisms. We designed a novel method for longitudinal and quantitative in vivo cell tracking, based on the superior visualization abilities of classical X-ray computed tomography (CT), combined with state-of-the-art nanotechnology. Herein, T-cells were transduced to express a melanoma-specific T-cell receptor and then labeled with gold nanoparticles (GNPs) as a CT contrast agent. The GNP-labeled T-cells were injected intravenously to mice bearing human melanoma xenografts, and whole-body CT imaging allowed examination of the distribution, migration, and kinetics of T-cells. Using CT, we found that transduced T-cells accumulated at the tumor site, as opposed to nontransduced cells. Labeling with gold nanoparticles did not affect T-cell function, as demonstrated both in vitro, by cytokine release and proliferation assays, and in vivo, as tumor regression was observed. Moreover, to validate the accuracy and reliability of the proposed cell tracking technique, T-cells were labeled both with green fluorescent protein for fluorescence imaging, and with GNPs for CT imaging. A remarkable correlation in signal intensity at the tumor site was observed between the two imaging modalities, at all time points examined, providing evidence for the accuracy of our CT cell tracking abilities. This new method for cell tracking with CT offers a valuable tool for research, and more importantly for clinical applications, to study the fate of immune cells in cancer immunotherapy.

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Cell-based therapies utilize transplantation of living cells with therapeutic traits to alleviate numerous diseases and disorders. The use of such biological agents is an attractive alternative for diseases that existing medicine cannot effectively treat. Although very promising, translating cell therapy to the clinic has proven to be challenging, due to inconsistent results in preclinical and clinical studies. To examine the underlying cause for these inconsistencies, it is crucial to noninvasively monitor the accuracy of cell injection, and cell survival and migration patterns. The combination of classical imaging techniques with cellular contrast agents-mainly nanotechnological-based-has enabled significant developments in cell-tracking methodologies. One novel methodology, based on computed tomography (CT) as an imaging modality and gold nanoparticles (AuNPs) as contrast agents, has recently gained interest for its clinical applicability and cost-effectiveness. Studies have shown that AuNPs can be used to efficiently label a variety of cell types, including stem cells and immune cells, without damaging their therapeutic efficacy. Successful in vivo experiments have demonstrated noninvasive, quantitative and longitudinal cell tracking with high sensitivity. This concept has the potential to be used not only as a research tool, but in clinical settings as well. WIREs Nanomed Nanobiotechnol 2018, 10:e1480. doi: 10.1002/wnan.1480 This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Triplet−triplet annihilation upconversion (TTA-UC) is an unconventional photophysical process that yields high-energy photons from low-energy incident light and offers pathways for innovation across many technologies, including solar energy harvesting, photochemistry, and optogenetics. Within aromatic organic chromophores, TTA-UC is achieved through several consecutive energy conversion events that ultimately fuse two triplet excitons into a singlet exciton. In chromophores where the singlet exciton is roughly isoergic with two triplet excitons, the limiting step is the triplet−triplet annihilation pathway, where the kinetics and yield depend sensitively on the energies of the lowest singlet and triplet excited states. Herein we report up to 40-fold improvements in upconversion quantum yields using molecular engineering to selectively tailor the relative energies of the lowest singlet and triplet excited states, enhancing the yield of triplet−triplet annihilation and promoting radiative decay of the resulting singlet exciton. Using this general and effective strategy, we obtain upconversion yields with red emission that are among the highest reported, with remarkable chemical stability under ambient conditions.