posted on 2023-12-12, 03:04authored byAngelea Maestas-Olguin, Marian Olewine, Sheymah Thabata, Johanna Tsala Ebode, Mariella Arcos, Jacob Krawchuck, Eric N. Coker, Adrian J. Brearley, Xiang Xue, John Watt, Achraf Noureddine, C. Jeffrey Brinker
The use of exogenous nucleic acid technologies to modulate
aberrant
protein expression resulting from genetic mutations is a promising
therapeutic approach for the treatment of diseases such as advanced
prostate cancer (PC). The promise of nucleic-based therapeutics is
dependent on the development of platforms that effectively protect
nucleic acids from nuclease degradation and deliver the nucleic acids
to the cytosol of target cells. In this work, we present the development
of a divalent metal-mediated nucleic acid entrapment strategy with
a porous silica matrix. This simple strategy results in efficient
loading percentages of both siRNA (>60%) and mRNA (>80%) as
well as
their release within relevant biological environments (80%). Additionally,
our data supports that the current method reduces endosomal entrapment
and supports the lipid coating of mesoporous silica nanoparticles
(LC-MSNs). The metal-enhanced nanosystem is assessed for biocompatibility,
stability, and circulation within in vitro, ex ovo, and in vivo models
of PC.