Abstract
Biologically derived metal–organic frameworks (Bio-MOFs) are significant, as they can be used in cutting-edge biomedical applications such as targeted gene delivery. Herein, adenine (Ade) and unnatural amino acids coordinate with Zn2+ to produce biocompatible frameworks, KBM-1 and KBM-2, with extremely defined porous channels. They feature an accessible Watson–Crick Ade face that is available for further hydrogen bonding and can load single-stranded DNA (ssDNA) with 13 and 41% efficiency for KBM-1 and KBM-2, respectively. Treatment of these frameworks with thymine (Thy), as a competitive guest for base pairing with the Ade open sites, led to more than 50% reduction of ssDNA loading. Moreover, KBM-2 loaded Thy-rich ssDNA more efficiently than Thy-free ssDNA. These findings support the role of the Thy-Ade base pairing in promoting ssDNA loading. Furthermore, theoretical calculations using the self-consistent charge density functional tight-binding (SCC-DFTB) method verified the role of hydrogen bonding and van der Waals type interactions in this host–guest interface. KBM-1 and KBM-2 can protect ssDNA from enzymatic degradation and release it at acidic pH. Most importantly, these biocompatible frameworks can efficiently deliver genetic cargo with retained activity to the cell nucleus. We envisage that this class of Bio-MOFs can find immediate applicability as biomimics for sensing, stabilizing, and delivering genetic materials.
Highlights
Prospective utilization of metal−organic frameworks (MOFs) for biomedical and pharmaceutical applications has progressed significantly over the past decade
King Abdullah University of Science and Technology (KAUST) bioMOF-2 (KBM-2) is a neutral framework with the molecular formula [Zn8(Ade)4(L)3]· xGuest}n, and it crystallizes in the triclinic crystal system with space group P1̅ (Table S2)
The role of Ade-Thy base pairing in promoting single-stranded DNA (ssDNA) loading was successfully verified using Thy competitive-guest binding and theoretical calculations
Summary
Prospective utilization of metal−organic frameworks (MOFs) for biomedical and pharmaceutical applications has progressed significantly over the past decade. Biocompatible smart hybrid materials with competent cell permeability, high stability and appropriate pharmacokinetics have been reported for delivering drug/cargo into specific cells.[18,19] Prospective synthetic systems should be nature-derived carriers as they gratify most of these key features, such as water solubility, biocompatibility, and high cellular uptake efficiency with marginal toxicity Biomolecules such as peptides, sugars, curcumin, and nucleobases have emerged as promising building blocks for constructing more biologically derived MOFs (Bio-MOFs) or metal-biomolecule frameworks (MBioFs).[20−26] Mimicking natural designs using adenine (Ade) as a building block is a great approach to achieve natural nucleobase hydrogen bonding reminiscence of the Watson−Crick double-stranded DNA assembly. To the best of our knowledge, this is the first report of ssDNA loading and condensation on BioMOFs assisted by complementary base pairing
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
