Targeted and effective?

Getting a therapeutic to the target organ or tissue is only half the battle for most diseases, as most drugs need to be internalized by the affected cells to be effective.

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PASADENA, Calif.—Getting a therapeutic to the target organ or tissue is only half the battle for most diseases, as most drugs need to be internalized by the affected cells to be effective. Recently, researchers at CalTech, UCLA, and Germany's University of Freiburg looked at the impact of adding targeting molecules to siRNA nanoparticles on both biodistribution and tumor cell uptake.
 
As they report in PNAS, the researchers used micoPET and microCT to monitor the biodistribution and tumor localization of nanoparticles comprised of 64Cu-DOTA-conjugated anti-luciferase siRNA, with and without transferring-based targeting. Examining mice with luciferase-expressing tumors, the researchers noted the nanoparticles behaved almost identically regardless of whether they were targeted, suggesting that the transferring moieties had no impact.
 
Using bioluminescence imaging, however, the researchers found that transferrin-targeted nanoparticles had a more significant impact on tumor luciferase expression than nontargeted nanoparticles, reducing expression 50% lower. This result suggests that more siRNA from the targeted nanoparticles is being internalized within the tumor cells.
 
The researchers suggest that these results show that both physicochemical properties as well as the presence of targeting ligands should be considered in the development of future imaging and therapeutic agents.


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