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Multiscale Profiling of Nanoscale Metal-Organic Framework Biocompatibility and Immune Interactions
Yunhui Zhuang1, Bárbara B Mendes2, Dhruv Menon1
1Adsorption & Advanced Materials Laboratory (AAML), Department of Chemical Engineering and Biotechnology, University of Cambridge, Philippa Fawcett Drive, Cambridge, CB3 0AS, UK.
Advanced Healthcare Materials
|August 7, 2025
Summary
A new "Safety-by-Design" pipeline using machine learning and advanced models predicts and validates the immunotoxicity of metal-organic frameworks (MOFs) for nanomedicine, ensuring safer clinical translation.
Area of Science:
- Nanomedicine
- Materials Science
- Immunotoxicology
Background:
- Clinical translation of metal-organic frameworks (MOFs) is limited by unknown immune interactions and in vivo immunotoxicity.
- A comprehensive understanding of MOF immunotoxicity is crucial for developing safe nanomedicines.
Purpose of the Study:
- To establish and validate a "Safety-by-Design" pipeline integrating machine learning (ML) and experimental models for MOF immunotoxicity assessment.
- To systematically profile the immunotoxicity of clinically relevant MOFs and de-risk their development.
Main Methods:
- Utilized a multi-stage workflow combining in silico ML screening, ex vivo human blood studies, and targeted in vivo models.
- Assessed immunotoxicity by analyzing cytotoxicity, cytokine induction (IL-6), and immune cell activation.
- Evaluated four MOFs: NU-901, PCN-222, UiO-66, and ZIF-8.
Main Results:
- In silico screening accurately identified NU-901 and ZIF-8 as potential immune hazards.
- Ex vivo studies confirmed NU-901's selective cytotoxicity to monocytes and ZIF-8's pro-inflammatory effects (IL-6 induction).
- UiO-66 and PCN-222 showed high biocompatibility ex vivo and minimal, transient immune activation in vivo.
Conclusions:
- The "Safety-by-Design" pipeline provides a validated, resource-efficient roadmap for preclinical immunotoxicity assessment of nanomedicines.
- This approach accelerates the safe clinical translation of MOFs and other advanced nanomaterials by rationalizing safety evaluations.
