PARK7 mRNA encodes DJ-1 protein, which functions as a protective agent against oxidative stress and cell damage within the brain cells. Mutations in the mRNA can lead to reduced production of DJ-1 and initiate brain diseases such as Parkinson’s disease. Transport of appropriate mRNA to damaged brain cells may provide a suitable treatment. Mesoporous silica nanoparticles (MSNPs), particularly pore-expanded and dye-labeled varieties, are regarded as potential carriers for large therapeutic agents such as mRNA. This study explored the influence of alterations in reaction conditions on the structural characteristics of MSNPs to produce nanoparticles with favorable characteristics for delivering large therapeutic agents to target sites. One-stage and two-stage procedures were compared for the introduction of 3-aminopropyltriethoxysilane (APTES) and APTES-dye adduct, in conjunction with two different surfactants, cetyltrimethylammonium bromide (CTAB) and cetyltrimethylammonium chloride (CTAC). Analysis of the MSNPs shows that the two-stage method using CTAB as a surfactant produced amine-functionalized, dye-labelled particles with smaller overall size and better uniformity than the one-stage approach. However, due to their small pore size (<10 nm), these particles were unable to encapsulate the PARK7 mRNA (926 nucleotides). The one-stage method via CTAC produced MSNPs with large (150 nm), broad pore distribution (10–20 nm), and high aggregation, limiting their suitability for brain-targeted gene delivery. In comparison, the two-stage method using CTAC yielded well-ordered MSNPs with an optimal size (80 nm) and pore diameters (15–20 nm), enabling effective encapsulation of the large PARK7 mRNA and offering strong potential for future brain gene therapy studies.
Details
Title
Optimizing mesoporous silica synthesis procedures to enhance their potential as nanoplatforms in therapeutic applications
Authors/Creators
Olia Alijanpourtolouti
Sulev Koks - Murdoch University, Personalised Medicine Centre
Gamini Senanayake - Murdoch University, Centre for Water, Energy and Waste
David James Henry - Murdoch University, Centre for Sustainable Farming Systems
School of Mathematics, Statistics, Chemistry and Physics; Centre for Water, Energy and Waste; Personalised Medicine Centre; Centre for Sustainable Farming Systems; Genomics Core Research Facility