Ocean acidification caused by increasing emission of carbon dioxide (CO 2 ) is expected to have profound impacts on marine ecological processes, including the formation and evolution of harmful algal blooms (HABs). We designed a set of experiments in the laboratory to examine the effects of increasing CO 2 on the growth and toxicity of a toxic dinoflagellate Alexandrium minutum producing paralytic shellfish toxins (PSTs). It was found that high levels of CO 2 (800 and 1200 ppm) significantly promoted the growth of A. minutum compared to the group (400 ppm) representing the current CO 2 level. The total yields of PSTs by A. minutum , including both intracellular and extracellular toxins, were significantly enhanced, probably due to the induction of core enzyme activity and key amino acids synthesis for PST production. More interestingly, high level of CO 2 promoted the transformation from gonyautoxin2&3 to gonyautoxin1&4 and depressed the release of PSTs from inside to outside of the cells. All these processes collectively led to an apparent increase of A. minutum toxicity. Our study demonstrated that rising CO 2 would increase the risk of toxic A. minutum based on the comprehensive analyses of different processes including algal growth and toxin synthesis, transformation and release.
Antibody-drug conjugates (ADCs) are being developed worldwide with the potential to revolutionize current cancer treatment strategies. However, off-target toxicity caused by the instability of linkers remains one of the main issues to be resolved. Developing a novel photocontrol-ADC with good stability and photocontrolled release seemed to be an attractive and practical solution. In this study, we designed, for the first time, a novel ultraviolet (UV) light-controlled ADC by carefully integrating the UV-cleavable o -nitro-benzyl structure into the linker. Our preliminary work indicated that the ADC exhibited good stability and photocontrollability while maintaining a targeting effect similar to that of the naked antibody. Upon irradiation with UV light, the ADC rapidly released free cytotoxins and exerted significant cytotoxicity toward drug-resistant tumor cells. Compared to those of the unirradiated cells, the EC 50 values of ADCs increased by up to 50-fold. Furthermore, our research confirmed that the degradation products of unirradiated ADC, Cys- 1a, were relatively less toxic, thus potentially reducing the off-target toxicity caused by nonspecific uptake of ADCs. The novel design strategy of UV light-controlled ADCs may provide new perspectives for future research on ADCs and promote the development of photocontrol systems.
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