Induction of apoptosis in Trypanosoma brucei following endocytosis of ultra-small noble metal nanoclusters.

• Trypanosoma brucei endocytosed noble metal nanoclusters (Ag 2 S-NC@MPA and AuNC@GSH) via the clathrin-dependent pathway. • NM-NCs displayed a dose-dependent anti-parasitic effect by inducing apoptosis in T. brucei. • Ag 2 S-NC@MPA mainly interacted with functional proteins located in the mitochondrion and endoplasmic reticulum. • AuNC@GSH interfered with activities of enzymes involved in mRNA maturation, protein degradation and signal transduction. [Display omitted] Trypanosoma brucei , the causative agent of African trypanosomiasis, is a unicellular protozoan with an intricate life cycle involving an insect vector and mammalian hosts. Trypanosomiasis remains a threat to the health of human beings and animals. Despite the rapid development of nanomedicine, there are few valuable reports on the application of nanoscience in protozoa, especially the lack of understanding of the mechanism. In this study, we investigated the endocytosis of two noble metal nanoclusters (NM-NCs), Ag 2 S-NC@MPA and AuNC@GSH in T. brucei. Both types of NC can be efficiently up-taken by T. brucei via a clathrin-dependent endocytosis pathway, and displayed in a dose-dependent anti-parasitic manner by inducing pathological alterations to apoptosis-associated organelles. The Ag 2 S-NC@MPA mainly interacted with functional proteins in the mitochondrion and endoplasmic reticulum, while the AuNC@GSH predominantly interfered with the biological activity of cytoplasmic enzymes involved in mRNA maturation, protein degradation and signal transduction. These data not only reveal the clathrin-dependent endocytosis pathway in T. brucei , but also open up a new avenue for NM-NC-based drug development for trypanosomiasis. [ABSTRACT FROM AUTHOR]