8KFD
Ferritin drug carrier(FDC) for encapsulated platinum (IV) prodrug for esophageal squamous cell carcinoma targeted therapy
Summary for 8KFD
| Entry DOI | 10.2210/pdb8kfd/pdb |
| Descriptor | Ferritin heavy chain, N-terminally processed, PLATINUM (II) ION, GLYCEROL, ... (7 entities in total) |
| Functional Keywords | ferritin, drug carrier, carcinoma therapy, transport protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 22134.25 |
| Authors | Chen, X. (deposition date: 2023-08-15, release date: 2024-05-29, Last modification date: 2024-12-18) |
| Primary citation | 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 Cited by 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: 38627234DOI: 10.1021/acsnano.4c00212 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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