Advanced Science, 31 December, 2024, DOI：https://doi.org/10.1002/advs.202413389
Ferritin-Based Supramolecular Assembly Drug Delivery System for Aminated Fullerene Derivatives to Enhance Tumor-Targeted Therapy
Baoli Zhang, Libin Yang, Yiliang Jin, Yicheng Lu, Jianru Li, Guoheng Tang, Yang Liu, Jiawei Huo, Ran Xu, Chunru Wang, Xiyun Yan, Jie Li, Kelong Fan
Abstract
Owing to their attractive antitumor effects, aminated fullerene derivatives are emerging as promising therapeutic drugs for cancer. However, their in vivo applications are severely limited due to cation toxicity. To address this problem, human heavy chain ferritin (HFn), possessing natural biocompatibility is utilized, to develop a novel supramolecular assembly drug delivery system. Specifically, tetra[4-(amino)piperidin-1-yl]-C60 (TAPC) is selected as the representative aminated fullerene, and a layer-by-layer assembly strategy is designed to controllably assemble TAPC with the negatively charged HFn into a hierarchical coassembly (H@T@H) via electrostatic interactions and hydrogen bonds. In this ordered multilayer structure, the surface displayed HFn endows the inner TAPC with biocompatibility, tumor-targeting and blood-brain barrier crossing ability. Additionally, the electrostatic assembly mode enables the acid-responsive disassembly of H@T@H to release TAPC in lysosomes. In the orthotopic glioma mouse model, the HFn-assembled TAPC (H@T@H) shows higher brain accumulation and a stronger inhibitory effect on glioma than polyethylene glycol (PEG)-coated TAPC. Moreover, in an experimental metastasis mouse model, H@T@H have significant preventive and therapeutic effects on tumor metastasis. Encouragingly, the ferritin-based supramolecular assembly strategy has been proven to have broad applicability for various aminated fullerene derivatives, showing promising potential for tackling the in vivo delivery challenges of cationic drugs.
文章链接：https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202413389
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