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Review
, 19 (6), 367-73

Nanovector Delivery of siRNA for Cancer Therapy

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Review

Nanovector Delivery of siRNA for Cancer Therapy

H Shen et al. Cancer Gene Ther.

Abstract

RNA interference holds the promise to knock down expression of every cancer gene. Both academic laboratories and pharmaceutical companies have committed heavily on manpower and financial resources to develop small interfering RNA (siRNA) cancer therapeutics over the last decade. Although significant advances have been made in the design of siRNA therapeutics and mechanism of action on cancer cell killing, there are still many hurdles to overcome including effective delivery of therapeutics in vivo. Nanotechnology has had an important role in the development of delivery vectors so far. This article summarizes current nanovectors for siRNA delivery, discusses technical challenges in overcoming biological barriers, and introduces the multistage vector system for tumor-specific delivery.

Figures

Figure 1
Figure 1. Scanning electron micrograph of blood vessels from normal and tumor tissues
Left: Smooth, tight endothelial cell monolayer covering the luminal surface of a normal blood vessel. Right: Disorganized endothelium of a tumor blood vessel. A gap is apparent at an open endothelial cell juncture. (Reproduced with permission from (61). Courtesy of Elsevier)
Figure 2
Figure 2. Schematic illustration of siRNA delivery with multistage vector
(a) The 1st stage porous silicon loaded with siRNA nanoparticles travels in the circulation, and attaches to the tumor vascular endothelium. (b) The 1st stage particle releases 2nd stage carrier nanoparticles through the vascular endothelium into tumor interstitium where they are taken up by tumor cells. (c) Possible routes of siRNA entry into tumor cells.
Figure 3
Figure 3. Uptake of microparticles by endothelial cells
HUVECs were incubated with 3.2 μm oxidized silicon microparticles at a ratio of 1:10 (cell/particle) for 15-60 min in a serum-free medium. Uptake of particles by HUVEC cells was imaged by SEM. (Reproduced with permission from (58). Courtesy of Elsevier)
Figure 4
Figure 4. Systemic delivery of MSV/EphA2 siRNA results in long-lasting in vivo gene silencing
Mice bearing human SKOV3ip1 orthotopic ovarian tumors were dosed once with MSV/ePhA2 siRNA. (A) Knockdown of EphA2 gene expression was confirmed by Western blot analysis. (B) Densitometric analysis to normalize EphA2 expression by β-actin. (C) Immunohistochemical analysis of EphA2 expression in tumor tissues. (Reproduced with permission from (50). Courtesy of American Association for Cancer Research)

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