The effective delivery of chemotherapeutic drugs to tumor sites is critical for cancer treatment and remains a significant challenge. The advent of nanomedicine has provided additional avenues for altering the in vivo distribution of drug payloads and increasing tumor localization. More recently, cell-derived nanoparticles, with their biocompatibility and unique biointerfacing properties, have demonstrated considerable utility for drug delivery applications. Here, we demonstrate that cell membrane-derived nanodiscs can be employed for tumor-targeted delivery. To bestow active targeting capabilities to the cellular nanodiscs, we utilize a modular functionalization strategy based on the SpyCatcher system. This enables the nanodiscs to be covalently modified with any targeting ligand labeled with a short SpyTag peptide sequence. As a proof-of-concept, a model chemotherapeutic doxorubicin is loaded into nanodiscs functionalized with an affibody targeting epidermal growth factor receptor. The resulting nanoformulation demonstrates strong tumor targeting both in vitro and in vivo, and it is able to significantly inhibit tumor growth in a murine breast cancer model.

中文翻译：

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细胞纳米圆盘的模块化功能化使化疗药物能够靶向递送到肿瘤中


化疗药物有效递送到肿瘤部位对于癌症治疗至关重要，并且仍然是一个重大挑战。纳米医学的出现为改变药物有效载荷的体内分布和增加肿瘤定位提供了额外的途径。最近，细胞来源的纳米颗粒凭借其生物相容性和独特的生物界面特性，在药物递送应用中显示出相当大的实用性。在这里，我们证明了细胞膜衍生的纳米圆盘可用于肿瘤靶向递送。为了赋予细胞纳米盘主动靶向能力，我们利用了基于 SpyCatcher 系统的模块化功能化策略。这使得纳米圆盘可以与任何用短 SpyTag 肽序列标记的靶向配体共价修饰。作为概念验证，将模型化疗阿霉素加载到纳米圆盘中，该纳米圆盘通过靶向表皮生长因子受体的亲和体功能化。所得纳米制剂在体外和体内均显示出强大的肿瘤靶向性，并且能够在小鼠乳腺癌模型中显著抑制肿瘤生长。