TY - JOUR
T1 - Surface engineering of metal-organic framework nanoparticles-based miRNA carrier
T2 - Boosting RNA stability, intracellular delivery and synergistic therapy
AU - Jin, Weiguang
AU - Li, Xin
AU - Argandona, Sergio Mercado
AU - Ray, Roslyn M.
AU - Lin, Marie Karen Tracy Hong
AU - Melle, Francesca
AU - Clergeaud, Gael
AU - Lars Andresen, Thomas
AU - Nielsen, Martin
AU - Fairen‐Jimenez, David
AU - Astakhova, Kira
AU - Qvortrup, Katrine
N1 - Publisher Copyright:
© 2024 Elsevier Inc.
PY - 2025
Y1 - 2025
N2 - MicroRNAs (miRNAs) are small noncoding RNAs that are critical for the regulation of multiple physiological and pathological processes, thus holding great clinical potential. However, the therapeutic applications of miRNAs are severely limited by their biological instability and poor intracellular delivery. Herein, we describe a dual-layers surface engineering strategy to design an efficient miRNA delivery nanosystem based on metal–organic frameworks (MOFs) incorporating lipid coating. The resulting nanoparticle system was demonstrated to protect miRNA from ribonuclease degradation, enhance cellular uptake and facilitate lysosomal escape. These ensured effective miRNA mediated gene therapy, which synergized with MOF-specific photodynamic therapy and pre-encapsulated doxorubicin (Dox) chemotherapy to provide a multifunctional with therapeutic effectiveness against cencer cells The mechanisms of miRNA binding and Dox loading were revealed, demonstrating the potential of the present MOFs surface-engineered strategy to overcome their inherent pore-size restriction for macromolecular miRNA carrying, enableefficient co-delivery. In vitro studies revealed the potential of our multifunctional system for miRNA delivery and the demonstrated the therapeutic effectiveness against cancer cells, thereby providing a versatile all-in-one MOFs strategy for delivery of nucleic acids and diverse therapeutic molecules in synergistic therapy.
AB - MicroRNAs (miRNAs) are small noncoding RNAs that are critical for the regulation of multiple physiological and pathological processes, thus holding great clinical potential. However, the therapeutic applications of miRNAs are severely limited by their biological instability and poor intracellular delivery. Herein, we describe a dual-layers surface engineering strategy to design an efficient miRNA delivery nanosystem based on metal–organic frameworks (MOFs) incorporating lipid coating. The resulting nanoparticle system was demonstrated to protect miRNA from ribonuclease degradation, enhance cellular uptake and facilitate lysosomal escape. These ensured effective miRNA mediated gene therapy, which synergized with MOF-specific photodynamic therapy and pre-encapsulated doxorubicin (Dox) chemotherapy to provide a multifunctional with therapeutic effectiveness against cencer cells The mechanisms of miRNA binding and Dox loading were revealed, demonstrating the potential of the present MOFs surface-engineered strategy to overcome their inherent pore-size restriction for macromolecular miRNA carrying, enableefficient co-delivery. In vitro studies revealed the potential of our multifunctional system for miRNA delivery and the demonstrated the therapeutic effectiveness against cancer cells, thereby providing a versatile all-in-one MOFs strategy for delivery of nucleic acids and diverse therapeutic molecules in synergistic therapy.
KW - Co-carrying
KW - Intracellular delivery
KW - Metal–organic frameworks
KW - miRNA stabilization
KW - Surface engineering
KW - Synergistic treatment
U2 - 10.1016/j.jcis.2024.08.074
DO - 10.1016/j.jcis.2024.08.074
M3 - Journal article
C2 - 39153246
AN - SCOPUS:85201509564
SN - 0021-9797
VL - 677
SP - 429
EP - 440
JO - Journal of Colloid and Interface Science
JF - Journal of Colloid and Interface Science
ER -