Receptor Specificity Engineering of TNF Superfamily Ligands

Artemisinin, the most famous anti‐malaria drug initially extracted from Artemisia annua
L., also exhibits anti‐tumor properties in vivo and in vitro. To improve its solubility and bioavaila‐
bility, multiple derivatives have been synthesized. However, to reveal the anti‐tumor mechanism
and improve the efficacy of these artemisinin‐type drugs, studies have been conducted in recent
years. In this review, we first provide an overview of the effect of artemisinin‐type drugs on the
regulated cell death pathways, which may uncover novel therapeutic approaches. Then, to over‐
come the shortcomings of artemisinin‐type drugs, we summarize the recent advances in two differ‐
ent therapeutic approaches, namely the combination therapy with biologics influencing regulated
cell death, and the use of nanocarriers as drug delivery systems. For the former approach, we dis‐
cuss the superiority of combination treatments compared to monotherapy in tumor cells based on
their effects on regulated cell death. For the latter approach, we give a systematic overview of
nanocarrier design principles used to deliver artemisinin‐type drugs, including inorganic‐based na‐
noparticles, liposomes, micelles, polymer‐based nanoparticles, carbon‐based nanoparticles,
nanostructured lipid carriers and niosomes. Both approaches have yielded promising findings in
vitro and in vivo, providing a strong scientific basis for further study and upcoming clinical trials.