8KFD

Ferritin drug carrier(FDC) for encapsulated platinum (IV) prodrug for esophageal squamous cell carcinoma targeted therapy

8KFD の概要

• エントリーDOI: 10.2210/pdb8kfd/pdb
• 分子名称: Ferritin heavy chain, N-terminally processed, PLATINUM (II) ION, GLYCEROL, ... (7 entities in total)
• 機能のキーワード: ferritin, drug carrier, carcinoma therapy, transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 22134.25

構造登録者

Chen, X. (登録日: 2023-08-15, 公開日: 2024-05-29, 最終更新日: 2024-12-18)

主引用文献

Jiang, B.,Chen, X.,Wang, S.,Wang, S.,Ma, S.,Lu, Y.,Ma, L.,Liang, Q.,Xiao, H.,Zhang, L.,Yan, X.,Fan, K.
Structure-Guided Design of Ferritin-Platinum Prodrugs for Targeted Therapy of Esophageal Squamous Cell Carcinoma.
Acs Nano, 18:11217-11233, 2024

PubMed Abstract: Due to its intrinsic tumor-targeting attribute, limited immunogenicity, and cage architecture, ferritin emerges as a highly promising nanocarrier for targeted drug delivery. In the effort to develop ferritin cage-encapsulated cisplatin (CDDP) as a therapeutic agent, we found unexpectedly that the encapsulation led to inactivation of the drug. Guided by the structural information, we deciphered the interactions between ferritin cages and CDDP, and we proposed a potential mechanism responsible for attenuating the antitumor efficacy of CDDP encapsulated within the cage. Six platinum prodrugs were then designed to avoid the inactivation. The antitumor activities of these ferritin-platinum prodrug complexes were then evaluated in cells of esophageal squamous cell carcinoma (ESCC). Compared with free CDDP, the complexes were more effective in delivering and retaining platinum in the cells, leading to increased DNA damage and enhanced cytotoxic action. They also exhibited improved pharmacokinetics and stronger antitumor activities in mice bearing ESCC cell-derived xenografts as well as patient-derived xenografts. The successful encapsulation also illustrates the critical significance of comprehending the interactions between small molecular drugs and ferritin cages for the development of precision-engineered nanocarriers.

PubMed: 38627234
DOI: 10.1021/acsnano.4c00212

実験手法

X-RAY DIFFRACTION (1.8 Å)