Senolytics and senostatics as adjuvant tumour therapy

Cell senescence is a driver of ageing, frailty, age-associated disease and functional decline. In oncology, tumour cell senescence may contribute to the effect of adjuvant therapies, as it blocks tumour growth. However, this is frequently incomplete, and tumour cells that recover from senescence may gain a more stem-like state with increased proliferative potential. This might be exaggerated by the induction of senescence in the surrounding niche cells. Finally, senescence will spread through bystander effects, possibly overwhelming the capacity of the immune system to ablate senescent cells. This induces a persistent system-wide senescent cell accumulation, which we hypothesize is the cause for the premature frailty, multi-morbidity and increased mortality in cancer survivors. Senolytics, drugs that selectively kill senescent cells, have been developed recently and have been proposed as second-line adjuvant tumour therapy. Similarly, by blocking accelerated senescence following therapy, senolytics might prevent and potentially even revert premature frailty in cancer survivors. Adjuvant senostatic interventions, which suppress senescence-associated bystander signalling, might also have therapeutic potential. This becomes pertinent because treatments that are senostatic in vitro (e.g. dietary restriction mimetics) persistently reduce numbers of senescent cells in vivo, i.e. act as net senolytics in immunocompetent hosts

Giant Zeeman splitting in nucleation-controlled doped CdSe:Mn2+ quantum nanoribbons

Doping of semiconductor nanocrystals by transition-metal ions has attracted tremendous attention owing to their nanoscale spintronic applications. Such doping is, however, difficult to achieve in low-dimensional strongly quantum confined nanostructures by conventional growth procedures. Here we demonstrate that the incorporation of manganese ions up to 10% into CdSe quantum nanoribbons can be readily achieved by a nucleation-controlled doping process. The cation-exchange reaction of (CdSe) 13 clusters with Mn 2+ ions governs the Mn 2+ incorporation during the nucleation stage. This highly efficient Mn 2+ doping of the CdSe quantum nanoribbons results in giant exciton Zeeman splitting with an effective g-factor of 600, the largest value seen so far in diluted magnetic semiconductor nanocrystals. Furthermore, the sign of the s-d exchange is inverted to negative owing to the exceptionally strong quantum confinement in our nanoribbons. The nucleation-controlled doping strategy demonstrated here thus opens the possibility of doping various strongly quantum confined nanocrystals for diverse applications.close6