Avila Flores Lab
The Avila-Flores group specializes in the development of physical and chemical drug delivery methods. A major area of focus is the use of peptide-based materials that self-assembly into vesicular nanoparticles. These capsules, named BAPCs (for Branched Amphipathic Peptide Capsules), facilitate the internalization of nucleic acids into cells. In addition, Dr. Flores team also explores the use photoporation as a powerful tool for drug delivery.
1.Branched amphiphilic peptide capsules (BAPCs) as a delivery system for mRNA.
In this project, we are testing the ability of BAPCs to deliver therapeutic mRNA in murine models. Similarly to PEG, mRNA shields the BAPC cationic surface and prevents early degradation by the mononuclear phagocytic system (MPS), enhancing with this its circulation time and therapeutics effects. In addition, BAPCs resists disruption by chaotropes, proteases, and temperature, thus displaying significant stability and shelf-life.
2.Oral delivery of dsRNA to inhibit gene expression in insects
Development of new and specific insect pest management methods is critical for overcoming pesticide resistance and collateral off-target killings. Gene silencing by feeding dsRNA to insects shows promise in this area. In this project we aim to use BAPCs to facilitate the cellular uptake of lethal dsRNA by insects through feeding. The insect diets included dsRNA with and without complexation with BAPCs. We are currently testing insect species come from different orders with different feeding mechanisms: Tribolium castaneum, Acyrthosiphon pisum, Periplaneta americana, Popillia japonica and Spodoptera frugiperda.
3.Intracellular Delivery of Drugs Using Laser-Activated Nanoparticles
Fungal infections are becoming a global health problem. A major limiting factor for the development of antifungals is the high impermeability of the rigid and thick fungal cell wall. Compared to mammalian cells, fungal cells are more resilient to perforation due to the presence of this carbohydrate armor. We are developing a new approach based on the generation of transient breaks, or pores, in the cell wall. Breaks are generated by cavitation and shock waves resulting from the irradiation of gold nanoparticles (AuNPs) with a femtosecond infrared laser. Such an approach enabled the delivery of membrane impermeable molecules into fungal cells. This methodology could potentially be adapted to clinical settings by adding topical aqueous solutions containing AuNPs and the antifungal agent to the affected area, followed by subsequent exposure to short laser pulses. The use of specific fungal drugs such as siRNA will allow to target and destroy exclusively fungal transcripts, limiting undesired effects on the mammalian cells.