RT Journal Article
T1 Clickable polymer-based coatings for modulating the interaction of metal-organic framework nanocrystals with living cells
A1 Cedrún Morales, Manuela
A1 Migliavacca, Martina
A1 Ceballos Guzmán, Manuel
A1 Pérez Maseda, Marta
A1 Zampini, Giulia
A1 Alameda Felgueiras, María Teresa
A1 Ostolaza-Paraiso, Jon
A1 Juanes Carrasco, Marisa
A1 Rincón, Irene
A1 Fairen-Jimenez, David
A1 Montenegro García, Javier
A1 Horcajada, Patricia
A1 Polo Tobajas, Ester
A1 Pelaz García, Beatriz
A1 Pino González de la Higuera, Pablo Alfonso del
K1 Metal–organic-frameworks
K1 Click chemistry
K1 Polymer coating
K1 Functionalization
K1 Nanocrystal-cell interactions
AB Nanosized microporous metal-organic-frameworks (NMOFs) serve as versatile drug delivery systems capable of navigating complex microenvironments and interacting with cells in specific tissues. The physicochemical properties of NMOFs, such as size, composition, porosity, colloidal stability, and external surface functionalization are essential for their success as efficient carriers. This study introduces a flexible, clickable coating using an amphiphilic polymer derivatized with dibenzo cyclooctyne groups as a universal, postsynthetic functionalization tool. To prove its universality, nanosized MOFs with different structure and composition (UiO-67, NU-1000, PCN-222, and ZIF-8) were produced with high monodispersity and were coated with a clickable, amphiphilic polymer. The resulting polymer-coated NMOFs display exceptional colloidal and structural stability in different biologically relevant media. For comparative purposes, we selected two size-equivalent NMOFs, ZIF-8 and UiO-67, which were functionalized with a library of biologically relevant azide-derivatized (macro)molecules, including poly(ethylene glycol), mannose, and a dynein-binding cell-penetrating peptide, using a bioorthogonal reaction. The choice of ZIF-8 and UiO-67, both 150 nm in size but with distinct coordination and surface chemistries, is pivotal due to their differing acid and base stability characteristics, which may potentially influence their performance in cellular environments. To track their performance in vitro, the NMOFs were loaded with cresyl violet, a common histological stain and lysosomal marker. Cellular internalization of the surface-functionalized NMOFs was markedly governed by their distinct (macro)molecule characteristics. This demonstrates that surface properties critically influence uptake efficiency, while also highlighting the versatility and effectiveness of the proposed coating strategy. In particular, the one functionalized with the dynein-binding peptide demonstrated a markedly higher rate of cellular internalization compared to other NMOFs. In contrast, derivatizations with mannose and poly(ethylene glycol) are associated with a substantial reduction in cellular uptake, suggesting stealth behavior. These results provide a bioorthogonal and versatile alternative for the external surface engineering of NMOFs, aiming to improve targeted drug delivery effectiveness.
PB American Chemical Society
SN 1944-8244
YR 2025
FD 2025
LK https://hdl.handle.net/10347/43552
UL https://hdl.handle.net/10347/43552
LA eng
NO Cedrún-Morales, M., Migliavacca, M., Ceballos, M., Perez-Maseda, M., Zampini, G., Felgueiras, M. T. A., Ostolaza-Paraiso, J., Juanes, M., Rincón, I., Fairen-Jimenez, D., Montenegro, J., Horcajada, P., Polo, E., Pelaz, B., & Del Pino, P. (2025). Clickable Polymer-Based Coatings for Modulating the Interaction of Metal–Organic Framework Nanocrystals with Living Cells. "ACS Applied Materials & Interfaces" ”, vol. 17 , 24994-25010
NO The authors thank the financial support of the European Research Council (starting grant #950421), the European Union (European Union NextGeneration EU/PRTR; H2020-MSCA-ITN #860942), the MICIU/AEI/10.13039/501100011033 (PID2023-152844NB-I00; PID2022-142338OB-100, PID2020-119206RB-I00, PID2023-151448NB-I00, CNS2023-144318), and the Xunta de Galicia (#ED431C 2022/18, #ED431B2023/19, #2021-CP090 and Centro de Investigacio\u0301n do Sistema Universitario de Galicia accreditation 2023-2027 #ED431G 2023/03). The authors are grateful for the use of RIAIDT-USC analytical facilities, particularly to Dr. Bruno Da Cun\u0303a Marin\u0303o (UNIDADE DE DIFRACCIO\u0301N DE RAIOS X)
DS Minerva
RD 24 abr 2026