Nanoscale Dihydroartemisinin@Zeolitic Imidazolate Frameworks for Enhanced Antigiardial Activity and Mechanism Analysis

Dihydroartemisinin (DHA) is an artificial semi-synthetic derivative of artemisinin (ART) with enhanced anti-giardial potential. However, the clinical application of DHA is limited by its low solubility and poor selectivity. The drug's absorption directly affects its effect on the cell; the mechanism research is also limited to its destruction of the cytoskeleton. Herein, zeolitic imidazolate framework-8 loaded DHA (DHA@Zif-8) was used to enhance the anti-giardial potential. DHA@Zif-8 can enhance cellular uptake, increase anti-giardial proliferation and encystation, and expand the endoplasmic reticulum compared to the DHA-treated group. Furthermore, the anti-giardial mechanism was investigated by RNA sequencing (RNA-seq). The results revealed that 123 genes were upregulated and 126 were down-regulated. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DHA@Zif-8 NPs impact metabolic functions in G. lamblia. The Real-Time Quantitative Reverse Transcription polymerase chain reaction verification results consist of RNA-seq data. In vivo, DHA@Zif-8 NPs showed a significant reduction in the eradication of the parasite from the stool and the intestine with marked improvement in the intestinal mucosal injury caused by G. lamblia trophozoites. This research provided the potential of utilizing DHA@ZIF-8 for developing an anti-protozoan drug for clinical applications.