The emergence of drug delivery using water stable metal-organic frameworks has elicited a lot of interest in their biocompatibility. However, few studies have been conducted on their stability in common buffers, cell media, and blood proteins. For these studies, single crystal ZIF-8 approximately 1 um in diameter were synthesized, incubated with common laboratory buffers, cell media, and serum, and then characterized by PXRD, IR, DLS, and SEM. Time-resolved SEM and PXRD demonstrate that buffers containing phosphate and bicarbonate alter the appearance and composition of ZIF-8; however, cargo inside the ZIF-8 does not appear to leak out, in most of these buffers, even when the ZIF-8 itself is displaced by phosphates. On the other hand, blood proteins in serum dissolve ZIF-8, causing trapped biomolecules to escape. The study presented here suggests that ZIF-8 can undergo dramatic surface chemistry changes that may affect the interpretation of cellular uptake and cargo release data. On the other hand, it provides a rational explanation as to how ZIF-8 neatly dissolves in vivo.
Icosahedral virus-like particles (VLPs) derived from bacteriophages Qβ and PP7 encapsulating small-ultra red fluorescent protein (smURFP) were produced using a versatile supramolecualr capsid dissassemble-reassemble approach. The generated fluorescent VLPs display identical structural properties to their non-fluorescent analogs. Encapsulated smURFP shows indistinguishable photochemical properties to its unencapsulated counterpart, exhibits outstanding stability towards pH, and produces bright in vitro images following phagocytosis by macrophages. In vivo imaging allows biodistribution to be imaged at different time points. Ex vivo imaging of intravenously administered encapsulated smURFP reveleas localization in the liver and kidneys after 2 h blood circulation and substantial elimination after 16 h of imaging highlighting the potential application of these constructs as non-invasive in vivo imaging agents.
The increasing rate of resistance of bacterial infection against antibiotics requires next generation approaches to fight potential pandemic spread. The development of vaccines against pathogenic bacteria has been difficult owing, in part, to the genetic diversity of bacteria. Hence, there are many potential target antigens and little a priori knowledge of which antigen/s will elicit protective immunity. The painstaking process of selecting appropriate antigens could be avoided with whole-cell bacteria; however, whole-cell formulations typically fail to produce long-term and durable immune responses. These complications are one reason why no vaccine against any type of pathogenic E. coli has been successfully clinically translated. As a proof of principle, we demonstrate a method to enhance the immunogenicity of a model pathogenic E. coli strain by forming a slow releasing depot. The E. coli strain CFT073 was biomimetically mineralized within a metal–organic framework (MOF). This process encapsulates the bacteria within 30 min in water and at ambient temperatures. Vaccination with this formulation substantially enhances antibody production and results in significantly enhanced survival in a mouse model of bacteremia compared to standard inactivated formulations.
Artificial native-like lipid bilayer systems constructed from phospholipids assembling into unilamellar liposomes allow the reconstitution of detergent-solubilized transmembrane proteins into supramolecular lipid-protein assemblies called proteoliposomes, which mimic cellular membranes. Stabilization of these complexes remains challenging because of their chemical composition, the hydrophobicity and structural instability of membrane proteins, and the lability of interactions between protein, detergent, and lipids within micelles and lipid bilayers. In this work we demonstrate that metastable lipid, protein-detergent, and protein-lipid supramolecular complexes can be successfully generated and immobilized within zeolitic-imidazole framework (ZIF) to enhance their stability against chemical and physical stressors. Upon immobilization in ZIF bio-composites, blank liposomes, and model transmembrane metal transporters in detergent micelles or embedded in proteoliposomes resist elevated temperatures, exposure to chemical denaturants, aging, and mechanical stresses. Extensive morphological and functional characterization of the assemblies upon exfoliation reveal that all these complexes encapsulated within the framework maintain their native morphology, structure, and activity, which is otherwise lost rapidly without immobilization.
Hierarchical porous carbons (HPCs) hold great promise in energy-related applications owing to their excellent chemical stability and well-developed porous structures. Attention has been drawn toward developing new synthetic strategies and precursor materials that permit greater control over composition, size, morphology, and pore structure. There is a growing trend of employing metal–organic frameworks (MOFs) as HPC precursors as their highly customizable characteristics favor new HPC syntheses. In this article, we report a biomimetically grown bacterial-templated MOF synthesis where the bacteria not only facilitate the formation of MOF nanocrystals but also provide morphology and porosity control. The resultant HPCs show improved electrochemical capacity behavior compared to pristine MOF-derived HPCs. Considering the broad availability of bacteria and ease of their production, in addition to significantly improved MOF growth efficiency on bacterial templates, we believe that the bacterial-templated MOF is a promising strategy to produce a new generation of HPCs.
Virus-like particles (VLPs) are multifunctional nanocarriers that mimic the architecture of viruses. They can serve as a safe platform for specific functionalization and immunization, which provides benefits in a wide range of biomedical applications. In this work, a new generation immunophotothermal agent is developed that adjuvants photothermal ablation using a chemically modified VLP called bacteriophage Qβ. The design is based on the conjugation of near-infrared absorbing croconium dyes to lysine residues located on the surface of Qβ, which turns it to a powerful NIR-absorber called PhotothermalPhage. This system can generate more heat upon 808 nm NIR laser radiation than free dye and possesses a photothermal efficiency comparable to gold nanostructures, yet it is biodegradable and acts as an immunoadjuvant combined with the heat it produces. The synergistic combination of thermal ablation with the mild immunogenicity of the VLP leads to effective suppression of primary tumors, reduced lung metastasis, and increased survival time.
Vaccines are considered one of the most significant medical advancements in human history, as they have prevented hundreds of millions of deaths since their discovery; however, modern travel permits disease spread at unprecedented rates, and vaccine shortcomings like thermal sensitivity and required booster shots have been made evident by the COVID‐19 pandemic. Approaches to overcoming these issues appear promising via the integration of vaccine technology with biomaterials, which offer sustained‐release properties and preserve proteins, prevent conformational changes, and enable storage at room temperature. Sustained release and thermal stabilization of therapeutic biomacromolecules is an emerging area that integrates material science, chemistry, immunology, nanotechnology, and pathology to investigate different biocompatible materials. Biomaterials, including natural sugar polymers, synthetic polyesters produced from biologically derived monomers, hydrogel blends, protein–polymer blends, and metal–organic frameworks, have emerged as early players in the field. This overview will focus on significant advances of sustained release biomaterial in the context of vaccines against infectious disease and the progress made towards thermally stable “single‐shot” formulations. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease
<p>The emergence of drug delivery using water stable metal-organic frameworks has elicited a lot of interest in their biocompatibility. However, few studies have been conducted on their stability in common buffers, cell media, and blood proteins. For these studies, single crystal ZIF-8 approximately 1 um in diameter were synthesized, incubated with common laboratory buffers, cell media, and serum, and then characterized by PXRD, IR, DLS, and SEM. Time-resolved SEM and PXRD demonstrate that buffers containing phosphate and bicarbonate alter the appearance and composition of ZIF-8. Further, blood proteins in serum dissolve ZIF-8, causing trapped biomolecules to escape. The study presented here suggests that ZIF-8 can undergo dramatic surface chemistry changes that may affect the interpretation of cellular uptake and cargo release data. On the other hand, it provides a rational explanation as to how ZIF-8 neatly dissolves <i>in vivo</i>. </p>
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