Biology subjects

Meehan, B.

Publications and source records attributed to Meehan, B..

3 recordsLinked to original sources

bioRxiv2026

Cancer-derived Extracellular Vesicles for Targeted Delivery of EGFRvIII siRNA to Glioblastoma, Comparison of siRNA Loading Methods and Efficiency

BackgroundExtracellular vesicles (EVs) are nano and macro-sized, lipid-bound particles, involved in cellular communication. Interestingly, cancer-derived EVs show a heterologous and cross-species tumour tropism which makes them a potential tool for efficient delivery of therapeutic small interfering RNA (siRNA) to the tumour cells. MethodsEVs derived from glioblastoma cells (U373P and U373vIII) were loaded with EGFRvIII siRNA to develop a targeted therapeutic strategy against glioblastoma. EV biodistribution was evaluated using fluorescent indocyanine green (ICG) staining followed by ex vivo imaging. Different loading strategies, including passive loading, sonication, saponin-mediated membrane permeabilization, electroporation, and transfection were assessed for their efficiency in loading siRNA into EVs. The efficiency of each method was evaluated by nano flowcytometry, in vitro uptake assay followed by immunoblot (western blot) analysis. Eventually, the most effective formulation was tested for the systemic siRNA administration and selective tumour delivery in vivo, followed by evaluation of tumour size and EGFRvIII expression. ResultsHere, we showed that siRNA transfection into EVs was the most effective loading strategy, as confirmed by nano-flow cytometry, uptake assays, and western blot analysis, achieving over 90% knockdown efficiency in vitro for EVs carrying EGFRvIII siRNA. In vivo, EGFRvIII siRNA-loaded EVs homed to the tumour site and downregulated EGFRvIII expression compared with the PBS-siRNA control group; however, no significant tumour shrinkage was observed. ConclusionEGFRvIII-targeting, glioblastoma cell-derived EVs can be used as siRNA delivery carriers for targeted gene therapy in glioblastoma. However, further optimization of siRNA delivery and treatment duration is required.

pharmacology and toxicology↗

bioRxiv2022

A short-term decellularisation technique for porcine carotid arteries that conveys a structural stimulus to cells

In many cases, treatment for stenotic atherosclerotic lesions requires the use of bypass grafts to divert blood flow around the diseased vessel sections. Autologous vessels are considered the "gold standard" for bypass conduits; however, the shortage of healthy autologous vessels has resulted in an increasing focus on optimising synthetic, biological and/or tissue engineered vascular bypass grafts. While many of the previously published methods have been shown to fall short of producing an ideal TEVG, this report presents a decellularisation process that produces an acellular vascular graft that is efficient, cost effective, and could be readily automated. The resulting graft can be used "off the shelf", has preserved arterial structure and mechanical properties, and conforms to decellularisation criteria regarding the sufficient removal of cellular and genetic components. Additionally, the graft does not require any priming, supports molecular transport, can withstand supraphysiological pressures, and can support cell attachment and growth under physiological strain conditions whilst providing structural cues for cell adhesion and growth. Impact statementVascular disease remains the leading cause of mortality worldwide. In the absence of suitable autologous vessels, there currently exists a clear clinical need for off the shelf vascular grafts that can successfully bypass diseased arteries. This paper outlines a short-term method for obtaining such a graft. The technique used involves decellularising porcine carotid arteries whilst preserving arterial structure and mechanical properties and is compliant with the international standard for implantable vascular prostheses: EN ISO 7198:2017. Additionally, this protocol is cost and time effective, and produces reproducible "ready to use" acellular grafts that support molecular transport, can withstand supraphysiological pressures, and can support cell attachment and growth with controlled structural cues under physiological strain conditions.

bioengineering↗

bioRxiv2022

Synthetic glycans that control gut microbiome structure mitigate colitis in mice

Relative abundances of bacterial species in the gut microbiome have been linked to many diseases. Species of gut bacteria are ecologically differentiated by their abilities to metabolize different glycans, making glycan delivery a powerful way to alter the microbiome to promote health. We describe the properties and therapeutic potential of chemically diverse synthetic glycans (SGs). Fermentation of SGs by gut microbiome cultures resulted in compound-specific shifts in taxonomic and metabolite profiles not observed with reference glycans, including prebiotics. Model enteric pathogens grow poorly on most SGs, potentially increasing their safety for at-risk populations. SGs increased survival, reduced weight loss, and improved clinical scores in mouse models of colitis. Synthetic glycans are thus a promising modality to improve health through selective changes to the gut microbiome.

microbiology↗