The structural perfection and multivalency of dendrimers have made them useful for biodelivery and bioactivity via peripheral functionalization and the modulation of core-forming structures and dendrimer generations. Yet only few dendrimers have shown inherent therapeutic activity arising from their inner repeating units. Here, we report the synthesis and characterization of a polyacylthiourea dendrimer with inherent potent anticancer activity and the absence of cytotoxicity in mice. The poly(ethylene glycol)-functionalized fourth generation of the dendrimer, which can be efficiently synthesized from sequential click reactions of orthogonal monomers, displays low in vivo acute and subacute toxicities yet potently inhibits tumour growth and metastasis. The dendrimer’s in vivo anticancer activity arises from the depletion of bioavailable copper and the subsequent inhibition of angiogenesis and cellular proliferation. When compared with some clinically used cytotoxin drugs, the dendrimer exerts inherent anticancer activity via non-cytotoxic pathways and leads to higher therapeutic efficacy, yet without cytotoxin-induced side effects.

树枝状大分子的结构完善和多价性使其通过外围功能化以及核心形成结构和树枝状大分子的生成调节，可用于生物传递和生物活性。然而，只有很少的树状聚合物显示出其内部重复单元所固有的治疗活性。在这里，我们报告具有固有的有效抗癌活性和小鼠中没有细胞毒性的聚酰基硫脲树状大分子的合成和表征。可以通过正交单体的连续点击反应有效合成的聚（乙二醇）-官能化的第四代树状聚合物，在体内显示出较低的急性和亚急性毒性，但有效地抑制了肿瘤的生长和转移。树枝状大分子的体内抗癌活性来自生物可利用铜的消耗以及随后对血管生成和细胞增殖的抑制。与某些临床使用的细胞毒素药物相比，树状大分子通过非细胞毒性途径发挥固有的抗癌活性，并导致更高的治疗功效，但没有细胞毒素引起的副作用。