Reticuloendothelial system blockade does not enhance siRNA-LNP circulation or tumor accumulation in mice.

ABSTRACT: One of the biggest challenges for siRNA-based therapeutics is intracellular delivery into the target cell, which can be facilitated by encapsulating siRNA in lipid nanoparticles (LNPs). In this study, we formulated D-Lin-MC3-DMA-LNPs encapsulating siRNA against the androgen receptor (AR), a key driver in prostate cancer. We effectively knocked down AR expression at both the mRNA as well as protein levels in vitro in AR-expressing prostate cancer cell lines. However, when moving to in vivo studies, siRNA-LNP efficacy is hindered by rapid clearance by the reticuloendothelial system (RES) in the liver and spleen. We evaluated whether transient RES blockade through systemic pre-administration of dextran sulfate or liposomes could extend the circulation time and enhance tumor accu

SUBMITTER: Escude Martinez de Castilla P 

PROVIDER: S-EPMC11925117 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature