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Clickable Polymer-Based Coatings for Modulating the Interaction of Metal-Organic Framework Nanocrystals with Living
Manuela Cedrún-Morales1, Martina Migliavacca2, Manuel Ceballos1
1Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS), Departamento de Física de Partículas, Universidade de Santiago de Compostela, 15705 Santiago de Compostela, Spain.
ACS Applied Materials & Interfaces
|April 21, 2025
Summary
Researchers developed a universal coating for nanosized metal-organic frameworks (NMOFs) to enhance drug delivery. Surface functionalization with a dynein-binding peptide significantly increased cellular uptake, demonstrating improved targeting capabilities.
Area of Science:
- Materials Science
- Nanotechnology
- Biomedical Engineering
Background:
- Nanosized metal-organic frameworks (NMOFs) are promising for drug delivery due to their tunable properties and ability to interact with biological systems.
- Effective drug delivery requires NMOFs with controlled physicochemical properties, including size, composition, porosity, colloidal stability, and surface functionalization.
Purpose of the Study:
- To introduce a flexible, clickable coating as a universal tool for postsynthetic functionalization of NMOFs.
- To evaluate the impact of surface functionalization on the cellular uptake and stability of NMOFs with distinct structures and chemistries.
Main Methods:
- Nanosized MOFs (UiO-67, NU-1000, PCN-222, ZIF-8) were synthesized with high monodispersity and coated with an amphiphilic polymer containing dibenzo cyclooctyne groups.
- Size-equivalent NMOFs (ZIF-8 and UiO-67) were functionalized with azide-derivatized molecules (PEG, mannose, dynein-binding peptide) via bioorthogonal click chemistry.
- The performance of functionalized NMOFs loaded with cresyl violet was assessed in vitro for cellular internalization.
Main Results:
- The polymer coating provided exceptional colloidal and structural stability to NMOFs in biologically relevant media.
- Surface functionalization significantly influenced cellular uptake; the dynein-binding peptide enhanced internalization, while PEG and mannose reduced it (stealth effect).
- ZIF-8 and UiO-67, despite similar size, exhibited differential cellular interactions based on their surface modifications.
Conclusions:
- The proposed clickable coating strategy offers a versatile and bioorthogonal method for external surface engineering of NMOFs.
- Surface functionalization critically governs NMOF uptake efficiency, enabling tailored interactions with specific cellular environments for improved targeted drug delivery.

