Cancer has become the leading cause of human death worldwide, and there is an urgent need to design and develop new oncology drugs. In this study, we report series of cationic amphiphilic
dendrons with different hydrophobic alkyl chains (Cn) and different generations (Gx) and demonstrate their use for anticancer applications. The results revealed that lower-generation
dendrons (G1) with a longer hydrophobic alkyl chain (C12 and C18) have stronger antitumor activity. Among these
dendrons, a lead candidate C12-G1 was identified that demonstrated excellent broad-spectrum antitumor activity in 7
cancer cell lines including highly metastatic
tumor cells, while simultaneously,
hemolysis was negligible. Mechanistic studies showed that C12-G1 could lead to cytoplasmic leakage and induce
cancer cell
necrosis through membrane disruption. In addition, C12-G1 showed potent inhibition of
tumor growth in a B16-F10
melanoma model. In conclusion, these findings demonstrate that the cationic amphiphilic
dendron might be a promising agent for anticancer application.