In some cancers mutant p53 promotes the occurrence, development, metastasis and drug resistance of tumours, with targeted protein degradation seen as an effective therapeutic strategy. However, a lack of specific autophagy receptors limits this. Here, we propose the synthesis of biomimetic nanoreceptors (NRs) that mimic selective autophagy receptors. The NRs have both a component for targeting the desired protein, mutant-p53-binding peptide, and a component for enhancing degradation, cationic lipid. The peptide can bind to mutant p53 while the cationic lipid simultaneously targets autophagosomes and elevates the levels of autophagosome formation, increasing mutant p53 degradation. The NRs are demonstrated in vitro and in a patient-derived xenograft ovarian cancer model in vivo. The work highlights a possible direction for treating diseases by protein degradation.

在一些癌症中，p53突变体促进肿瘤的发生、发展、转移和耐药性，靶向蛋白质降解被视为有效的治疗策略。然而，缺乏特定的自噬受体限制了这一点。在这里，我们建议合成模仿选择性自噬受体的仿生纳米受体（NR）。NR 既有用于靶向所需蛋白质（突变体 p53 结合肽）的成分，也有用于增强降解的成分（阳离子脂质）。该肽可以与突变型 p53 结合，而阳离子脂质同时靶向自噬体并提高自噬体形成水平，从而增加突变型 p53 的降解。NR 在体外和患者来源的异种移植卵巢癌体内模型中得到证实。这项工作突出了通过蛋白质降解治疗疾病的可能方向。