Metal–Organic Framework–Based Nanomedicines for Cancer Therapy: A Proposed Delivery Framework for Executable Cuproptosis
- 1School of Medicine, Huanghe Science and Technology College, Zhengzhou, People’s Republic of China
- 2School of Engineering, China Pharmaceutical University, Nanjing, People’s Republic of China
- 3School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
Abstract
Metal–organic frameworks (MOFs) can coordinate copper, catalytic sites and therapeutic cargo within one carrier, offering opportunities to control copper exposure and cellular susceptibility. Establishing their contribution to cuproptosis requires evidence connecting these design functions to copper delivery and the cell-death mechanism. This critical narrative review proposes “executable cuproptosis” as a delivery and evaluation framework for examining that connection. We assess selected MOF platforms across mechanistic validation, mitochondrial access, tumor context and translational requirements, with comparisons to other copper-delivery approaches. The reviewed examples show that material design can influence copper release, retention and treatment responses, while evidence linking these effects to mitochondrial copper and cuproptosis-specific causality remains uneven. Copper accumulation, carrier colocalization, oxidative stress and tumor inhibition support different claims; their interpretation depends on the measurement and functional controls. Combination studies require quantitative assessment of interaction and separate validation of each claimed death pathway or immune effect. Pharmacokinetic, biodistribution and long-term safety data remain incomplete, especially for organic linkers and transformation products, and the candidate biomarkers discussed here lack validation for clinical selection in MOF-enabled cuproptosis therapy. We identify priorities in mitochondrial copper measurement, tumor heterogeneity, component disposition and manufacturing reproducibility. The evidence remains predominantly preclinical. The framework organizes further development around testable links between delivery, mechanism and tumor state; its predictive value and the clinical benefit of MOF-enabled cuproptosis remain to be established.
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BibTeX
@article{fu2026metalorganic,
title = {{Metal–Organic Framework–Based Nanomedicines for Cancer Therapy: A Proposed Delivery Framework for Executable Cuproptosis}},
author = {Lina Fu and Li Wang and Hongjiang Li and Runbing Li and Xin Yue and Yuqi Cui and Congying Wang and Jensen King and Junfeng Huo},
journal = {International Journal of Nanomedicine},
year = {2026},
month = nov,
doi = {10.2147/ijn.s653099},
url = {https://doi.org/10.2147/ijn.s653099},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Metal–Organic Framework–Based Nanomedicines for Cancer Therapy: A Proposed Delivery Framework for Executable Cuproptosis
AU - Lina Fu
AU - Li Wang
AU - Hongjiang Li
AU - Runbing Li
AU - Xin Yue
AU - Yuqi Cui
AU - Congying Wang
AU - Jensen King
AU - Junfeng Huo
PY - 2026
DA - 2026/11/01
JO - International Journal of Nanomedicine
DO - 10.2147/ijn.s653099
UR - https://doi.org/10.2147/ijn.s653099
AB - Metal–organic frameworks (MOFs) can coordinate copper, catalytic sites and therapeutic cargo within one carrier, offering opportunities to control copper exposure and cellular susceptibility. Establishing their contribution to cuproptosis requires evidence connecting these design functions to copper delivery and the cell-death mechanism. This critical narrative review proposes “executable cuproptosis” as a delivery and evaluation framework for examining that connection. We assess selected MOF platforms across mechanistic validation, mitochondrial access, tumor context and translational requirements, with comparisons to other copper-delivery approaches. The reviewed examples show that material design can influence copper release, retention and treatment responses, while evidence linking these effects to mitochondrial copper and cuproptosis-specific causality remains uneven. Copper accumulation, carrier colocalization, oxidative stress and tumor inhibition support different claims; their interpretation depends on the measurement and functional controls. Combination studies require quantitative assessment of interaction and separate validation of each claimed death pathway or immune effect. Pharmacokinetic, biodistribution and long-term safety data remain incomplete, especially for organic linkers and transformation products, and the candidate biomarkers discussed here lack validation for clinical selection in MOF-enabled cuproptosis therapy. We identify priorities in mitochondrial copper measurement, tumor heterogeneity, component disposition and manufacturing reproducibility. The evidence remains predominantly preclinical. The framework organizes further development around testable links between delivery, mechanism and tumor state; its predictive value and the clinical benefit of MOF-enabled cuproptosis remain to be established.
SN - 1176-9114
SN - 1178-2013
ER -