BMI Center for Biomass Materials and Nanointerfaces, College of Biomass Science and Engineering, Sichuan University, Chengdu, Sichuan, 610065, China.
National Engineering Laboratory for Clean Technology of Leather Manufacture, Sichuan University, Chengdu, Sichuan, 610065, China.
Adv Sci (Weinh). 2023 Jun;10(18):e2207488. doi: 10.1002/advs.202207488. Epub 2023 Apr 18.
Cell-based therapies comprising the administration of living cells to patients for direct therapeutic activities have experienced remarkable success in the clinic, of which macrophages hold great potential for targeted drug delivery due to their inherent chemotactic mobility and homing ability to tumors with high efficiency. However, such targeted delivery of drugs through cellular systems remains a significant challenge due to the complexity of balancing high drug-loading with high accumulations in solid tumors. Herein, a tumor-targeting cellular drug delivery system (MAGN) by surface engineering of tumor-homing macrophages (Mφs) with biologically responsive nanosponges is reported. The pores of the nanosponges are blocked with iron-tannic acid complexes that serve as gatekeepers by holding encapsulated drugs until reaching the acidic tumor microenvironment. Molecular dynamics simulations and interfacial force studies are performed to provide mechanistic insights into the "ON-OFF" gating effect of the polyphenol-based supramolecular gatekeepers on the nanosponge channels. The cellular chemotaxis of the Mφ carriers enabled efficient tumor-targeted delivery of drugs and systemic suppression of tumor burden and lung metastases in vivo. The findings suggest that the MAGN platform offers a versatile strategy to efficiently load therapeutic drugs to treat advanced metastatic cancers with a high loading capacity of various therapeutic drugs.
基于细胞的疗法包括将活细胞施用于患者以进行直接治疗活动，在临床上取得了显著的成功，其中巨噬细胞由于其固有的趋化性迁移和高效归巢肿瘤的能力，在靶向药物递送方面具有巨大的潜力。然而，由于平衡高药物载药量和实体瘤中高积累的复杂性，通过细胞系统进行这种靶向药物递送仍然是一个重大挑战。在此，通过用生物响应性纳米海绵对归巢肿瘤的巨噬细胞（Mφs）进行表面工程，报道了一种肿瘤靶向细胞药物递送系统（MAGN）。纳米海绵的孔被铁-鞣酸复合物堵塞，作为门控物将包封的药物保持在到达酸性肿瘤微环境之前。进行分子动力学模拟和界面力研究，以提供基于多酚的超分子门控物对纳米海绵通道的“开-关”门控作用的机制见解。Mφ载体的细胞趋化性使药物能够有效靶向肿瘤，并在体内系统抑制肿瘤负担和肺转移。这些发现表明，MAGN 平台提供了一种通用策略，可以有效地负载治疗药物，以治疗具有高载药量的各种治疗药物的晚期转移性癌症。
