1 research outputs found
Tumor-Targeting Transferrin Nanoparticles for Systemic Polymerized siRNA Delivery in Tumor-Bearing Mice
Transferrin (TF) is widely used as
a tumor-targeting ligand for
the delivery of anticancer drugs because the TF receptor is overexpressed
on the surface of various fast-growing cancer cells. In this article,
we report on TF nanoparticles as an siRNA delivery carrier for in
vivo tumor-specific gene silencing. To produce siRNA carrying TF nanoparticles
(NPs), both TF and siRNA were chemically modified with sulfhydryl
groups that can build up self-cross-linked siRNA-TF NPs. Self-polymerized
5′-end thiol-modified siRNA (poly siRNA, psi) and thiolated
transferrin (tTF) were spontaneously cross-linked to form stable NPs
(psi-tTF NPs) under optimized conditions, and they could be reversibly
degraded to release functional monomeric siRNA molecules under reductive
conditions. Receptor-mediated endocytosis of TF induced rapid tumor-cell-specific
uptake of the psi-tTF NPs, and the internalized NPs resulted in a
downregulation of the target protein in red-fluorescent-protein-expressing
melanoma cancer cells (RFP/B16F10) with negligible cytotoxicity. After
systemic administration, the psi-tTF NPs showed marked accumulation
at the tumor, leading to successful target-gene silencing in vivo.
This psi-tTF NP system provided a safe and effective strategy for
in vivo systemic siRNA delivery for cancer therapy