Noh Ilkoo, Guo Zhongyuan, Wang Rui, Zhu Audrey T, Krishnan Nishta, Mohapatra Animesh, Gao Weiwei, Fang Ronnie H, Zhang Liangfang
Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego, La Jolla, CA 92093, USA.
Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, Shu and K.C. Chien and Peter Farrell Collaboratory, University of California San Diego, La Jolla, CA 92093, USA; Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
J Control Release. 2025 Feb 10;378:145-152. doi: 10.1016/j.jconrel.2024.12.004. Epub 2024 Dec 12.
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.
将化疗药物有效递送至肿瘤部位对癌症治疗至关重要，但仍是一项重大挑战。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更多途径。最近，细胞衍生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效用。在此，我们证明细胞膜衍生的纳米盘可用于肿瘤靶向递送。为赋予细胞纳米盘主动靶向能力，我们利用基于SpyCatcher系统的模块化功能化策略。这使得纳米盘能够与任何标记有短SpyTag肽序列的靶向配体进行共价修饰。作为概念验证，将模型化疗药物阿霉素装载到用靶向表皮生长因子受体的亲和体功能化的纳米盘中。所得的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。
