1 research outputs found
A Collaborative Assembly Strategy for Tumor-Targeted siRNA Delivery
A novel
“collaborative assembly” approach was reported
for the synthesis of an siRNA delivery system via a combination of
an electrostatically driven physical assembly and a facile click reaction-mediated
chemical assembly, which showed various advantages of more safety,
efficiency, and flexibility over the conventional approach that is
only based on the physical assembly. This strategy remained a high
cationic property of lipid-based complex for high siRNA loading capacity.
The direct chemical modification of a model polyanion, hyaluronic
acid (HA) on the cationic complex via click chemistry shielded the
positive charge of complex without affecting the siRNA binding, which
reduced the toxicity and enhanced the blood stability of the complex.
In addition, the incorporated polyanion might be prefunctionalized,
which endued the carrier with better biological characteristics such
as long circulating or tumor targeting. We demonstrated that the obtained
lipid-polymer hybrid nanoparticle (RSC-HA) using collaborative assembly
presented greater <i>in vivo</i> stability in the blood
for efficient tumor targeting than the physically assembled RSC/HA
in which HA was physically adsorbed on the complex. After endocytosis
into the cells, the protection of RSC-HA on siRNA turned off, while
the release of siRNA induced by the intracellular signals for enhanced
gene-silencing capacity. This combination of physical and chemical
assemblies provides an efficient strategy for the exploitation of
safe, stable, and functionalized siRNA delivery systems