2 research outputs found
Multifunctional Envelope-Type siRNA Delivery Nanoparticle Platform for Prostate Cancer Therapy
With
the capability of specific silencing of target gene expression,
RNA interference (RNAi) technology is emerging as a promising therapeutic
modality for the treatment of cancer and other diseases. One key challenge
for the clinical applications of RNAi is the safe and effective delivery
of RNAi agents such as small interfering RNA (siRNA) to a particular
nonliver diseased tissue (<i>e</i>.<i>g</i>.,
tumor) and cell type with sufficient cytosolic transport. In this
work, we proposed a multifunctional envelope-type nanoparticle (NP)
platform for prostate cancer (PCa)-specific <i>in vivo</i> siRNA delivery. A library of oligoarginine-functionalized and sharp
pH-responsive polymers was synthesized and used for self-assembly
with siRNA into NPs with the features of long blood circulation and
pH-triggered oligoarginine-mediated endosomal membrane penetration.
By further modification with ACUPA, a small molecular ligand specifically
recognizing prostate-specific membrane antigen (PSMA) receptor, this
envelope-type nanoplatform with multifunctional properties can efficiently
target PSMA-expressing PCa cells and silence target gene expression.
Systemic delivery of the siRNA NPs can efficiently silence the expression
of prohibitin 1 (PHB1), which is upregulated in PCa and other cancers,
and significantly inhibit PCa tumor growth. These results suggest
that this multifunctional envelope-type nanoplatform could become
an effective tool for PCa-specific therapy