DNA‐mimic for Specific Surface Functionalization of Zr‐MOFs for Bacterial Targeting
Year: 2026
Type: article
Abstract: ABSTRACT Nanosized metal–organic frameworks (MOFs) are versatile platforms used in biomedical applications due to their high loading capacity, large surface area, and tunable functionality. Without surface modifications, these nanoparticles lack cell specificity and are prone to aggregation and degradation in biological environments, reducing their effectiveness. Surface attachment of DNA via phosphate group coordination to zirconium‐based MOFs improves stability, but DNA binding remains non‐site‐specific due to the abundance of phosphate groups in its backbone, limiting DNA's addressability for further functionalization. To address this issue, we present a novel, significantly faster single‐step approach for the post‐synthesis modification of the external surface of PCN‐222 nanoparticles using an uncharged synthetic mimic of DNA, peptide nucleic acids (PNA). By using phosphate‐modified PNA, we achieve surface functionalization through coordination with the Zr 6 clusters on the MOF surface. The modification produced monodispersed nanoparticles and resulted in slowed drug‐release kinetics compared to unmodified nanoparticles. PNAs enhanced attachment efficiency and hybridization specificity compared to DNA coatings, allowing subsequent conjugation of protein targeting moieties and enabling bacterial targeting of drug‐loaded MOFs. This work introduces phosphotyrosine‐modified PNA as a superior, single‐step surface coating for PCN‐222, allowing controlled post‐functionalization with single‐stranded DNA (ssDNA) and expanding applications in biomedical and materials science.
Institution: University of Cambridge
Language: English
Subfield: Inorganic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,510
Awards: G1008117716, G108126998, G1255325603, G1417656367, G1835608419, G2001806450, G200406418, (re)Defining the nature of the Gram-negative outer membrane, EPSRC Centre for Doctoral Training (CDT) in Sensor Technologies and Application, Communication and Social Participation: collaborative Technologies for interaction And Learning, Heating triggered drug release from nanometric inorganic-metal organic framework composites, G2561383389, EPSRC Centre for Doctoral Training in Integrated Functional Nano (i4Nano), G3336248573, G3345895242, MICA: Multi-parametric and super-resolution imaging of amyloidogenic proteins, Next-Generation Biomimetic Nanomedicines, Development of single molecule techniques for nanoscale imaging of toxic protein species in vitro and in cells., G4226110756, Targeting membrane proteins in their native environments - Mass spectrometry meets cell biology, Mechanisms of neurotoxicity of amyloid aggregates., Mechanisms of neurotoxicity of amyloid aggregates., Next generation live super-resolution microscopy: development and application at the Cambridge Advanced Imaging Centre, G5859390703, G6230795418, G6510610700, G6705105409, G7413148874, G7707145192, G7731791180, G7823050896, Natural Interactive Walking, G7984235579, G8039008064, G8512683158, (re)Defining the nature of the Gram-negative outer membrane, G961685395
OpenAlex ID: W7162189734