治疗药物的高效和位点特异性递送仍然是癌症治疗中的关键挑战。传统的药物纳米载体（例如抗体药物缀合物）由于成本高昂而通常无法获得，并且可能导致严重的副作用，包括危及生命的过敏反应。在这里，这些问题通过采用创新的双印迹方法制造的超分子制剂的工程得到了克服。开发的分子印迹纳米颗粒（nanoMIP）靶向雌激素受体α（ERα）的线性表位，并装载化疗药物阿霉素。这些 nanoMIP 具有成本效益，并且与商业抗体对 ERα 的亲和力相媲美。当材料与在大多数乳腺癌 (BC) 中过度表达的 ERα 特异性结合时，通过受体介导的内吞作用实现核药物递送。因此，过度表达 ERα 的 BC 细胞系会显着增强细胞毒性，为 BC 的精准治疗铺平道路。通过在复杂的三维 (3D) 癌症模型中评估其药效，为 nanoMIP 的临床使用提供了概念验证，该模型无需动物模型即可捕获体内肿瘤微环境的复杂性。因此，这些发现凸显了 nanoMIP 作为一类有前景的新型药物化合物用于癌症治疗的潜力。© 2024 作者。 《Advanced Science》由 Wiley‐VCH GmbH 出版。

Efficient and site-specific delivery of therapeutics drugs remains a critical challenge in cancer treatment. Traditional drug nanocarriers such as antibody-drug conjugates are not generally accessible due to their high cost and can lead to serious side effects including life-threatening allergic reactions. Here, these problems are overcome via the engineering of supramolecular agents that are manufactured with an innovative double imprinting approach. The developed molecularly imprinted nanoparticles (nanoMIPs) are targeted toward a linear epitope of estrogen receptor alfa (ERα) and loaded with the chemotherapeutic drug doxorubicin. These nanoMIPs are cost-effective and rival the affinity of commercial antibodies for ERα. Upon specific binding of the materials to ERα, which is overexpressed in most breast cancers (BCs), nuclear drug delivery is achieved via receptor-mediated endocytosis. Consequentially, significantly enhanced cytotoxicity is elicited in BC cell lines overexpressing ERα, paving the way for precision treatment of BC. Proof-of-concept for the clinical use of the nanoMIPs is provided by evaluating their drug efficacy in sophisticated three-dimensional (3D) cancer models, which capture the complexity of the tumor microenvironment in vivo without requiring animal models. Thus, these findings highlight the potential of nanoMIPs as a promising class of novel drug compounds for use in cancer treatment.© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.