2 research outputs found
Reductively Responsive siRNA-Conjugated Hydrogel Nanoparticles for Gene Silencing
A critical need still remains for effective delivery
of RNA interference
(RNAi) therapeutics to target tissues and cells. Self-assembled lipid-
and polymer-based systems have been most extensively explored for
transfection with small interfering RNA (siRNA) in liver and cancer
therapies. Safety and compatibility of materials implemented in delivery
systems must be ensured to maximize therapeutic indices. Hydrogel
nanoparticles of defined dimensions and compositions, prepared via
a particle molding process that is a unique off-shoot of soft lithography
known as particle replication in nonwetting templates (PRINT), were
explored in these studies as delivery vectors. Initially, siRNA was
encapsulated in particles through electrostatic association and physical
entrapment. Dose-dependent gene silencing was elicited by PEGylated
hydrogels at low siRNA doses without cytotoxicity. To prevent disassociation
of cargo from particles after systemic administration or during postfabrication
processing for surface functionalization, a polymerizable siRNA pro-drug
conjugate with a degradable, disulfide linkage was prepared. Triggered
release of siRNA from the pro-drug hydrogels was observed under a
reducing environment while cargo retention and integrity were maintained
under physiological conditions. Gene silencing efficiency and cytocompatibility
were optimized by screening the amine content of the particles. When
appropriate control siRNA cargos were loaded into hydrogels, gene
knockdown was only encountered for hydrogels containing releasable,
target-specific siRNAs, accompanied by minimal cell death. Further
investigation into shape, size, and surface decoration of siRNA-conjugated
hydrogels should enable efficacious targeted in vivo RNAi therapies
Delivery of Multiple siRNAs Using Lipid-Coated PLGA Nanoparticles for Treatment of Prostate Cancer
Nanotechnology can provide a critical advantage in developing
strategies
for cancer management and treatment by helping to improve the safety
and efficacy of novel therapeutic delivery vehicles. This paper reports
the fabrication of polyÂ(lactic acid-<i>co</i>-glycolic acid)/siRNA
nanoparticles coated with lipids for use as prostate cancer therapeutics
made via a unique soft lithography particle molding process called
Particle Replication In Nonwetting Templates (PRINT). The PRINT process
enables high encapsulation efficiency of siRNA into neutral and monodisperse
PLGA particles (32–46% encapsulation efficiency). Lipid-coated
PLGA/siRNA PRINT particles were used to deliver therapeutic siRNA
in vitro to knockdown genes relevant to prostate cancer