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.

Metal–organic frameworks (MOFs) have been used to improve vaccine formulations by stabilizing proteins and protecting them against thermal degradation. This has led to increased immunogenicity of these proteinaceous therapeutics. In this work, we show that MOFs can also be used to protect the single-stranded DNA oligomer CpG to increase its immunoadjuvancy. By encapsulation of the phosphodiester CpG in the zinc-based MOF, zeolitic imidazolate framework-8, the DNA oligomer is protected from nuclease degradation and exhibits improved cellular uptake. As a result, we have been able to achieve drastically enhanced B-cell activation in splenocyte cultures comparable to the current state-of-the-art phosphorothioate CpG. Furthermore, we have made a direct comparison of micro- and nanosized MOFs for optimization of the particulate delivery of immunoadjuvants to maximize immune activation.

Studying the toxicity of zeolitic imidazolate framework-8 (ZIF-8) in context of intranasal administration will help researchers in building depot platforms for this non-invasive route of delivery.

No abstract

Plasmonic gold nanostructures are a prevalent tool in modern hypersensitive analytical techniques such as photoablation, bioimaging, and biosensing. Recent studies have shown that gold nanostructures generate transient nanobubbles through localized heating and have been found in various biomedical applications. However, the current method of plasmonic nanoparticle cavitation events has several disadvantages, specifically including small metal nanostructures (≤10 nm) which lack size control, tuneability, and tissue localization by use of ultrashort pulses (ns, ps) and high-energy lasers which can result in tissue and cellular damage. This research investigates a method to immobilize sub-10 nm AuNPs (3.5 and 5 nm) onto a chemically modified thiol-rich surface of Qβ virus-like particles. These findings demonstrate that the multivalent display of sub-10 nm gold nanoparticles (AuNPs) caused a profound and disproportionate increase in photocavitation by upward of 5−7-fold and significantly lowered the laser fluency by 4-fold when compared to individual sub-10 nm AuNPs. Furthermore, computational modeling showed that the cooling time of QβAuNP scaffolds is significantly extended than that of individual AuNPs, proving greater control of laser fluency and nanobubble generation as seen in the experimental data. Ultimately, these findings showed how QβAuNP composites are more effective at nanobubble generation than current methods of plasmonic nanoparticle cavitation.