Assembling well-defined MOF superstructures remains challenging as it requires easily removable hard templates or readily available immiscible solutions for an emulsion-based soft-template approach. In this work, a single-step emulsion-free soft...
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.
Targeted therapy has the potential to revolutionize medical
approaches
to bring us closer to an effective personalized therapy model. In
this work, we developed homologous-targeted magnetic nanowires coated
with biologics-loaded zeolitic imidazolate frameworks and cellular
membranes (ZNWs) to provide an increased therapeutic potential both in vitro and in vivo. In vitro, the uncoated ZNWs combined with laser treatment reduced cancer
cell viability by 34.6%, whereas the coated ZNWs combined with laser
treatment reduced cancer cell viability by 45.91%. In vivo, ZNWs accumulated selectively in MCF-7 cancer cells and maintained
a high intensity for up to 120 h, which reduced tumor growth significantly.
Combining gene and tumor ablation treatment with the homologous targeting
ability of ZNWs resulted in about 73% cell death. We believe that
using such an assembled coating to camouflage delivery vehicles has
effective outcomes in terms of improved targeting and therapeutic
efficiency and should be studied further for medical translation.
Effective immobilization and delivery of genetic materials is at the forefront of biological and medical research directed toward tackling scientific challenges such as gene therapy and cancer treatment. Herein we present a biologically inspired hydrogenbonded zinc adeninate framework (ZAF) consisting of zinc adeninate macrocycles that self-assemble into a 3D framework through adenine-adenine interactions. ZAF can efficiently immobilize DNAzyme with full protection against enzyme degradation and physiological conditions until it is successfully delivered into the nucleus. As compared to zeolitic imidazolate frameworks (ZIFs), ZAFs are twofold more biocompatible with a significant loading efficiency of 96 %. Overall, our design paves the way for expanding functional hydrogen-bonding-based systems as potential platforms for the loading and delivery of biologics.
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