Researchers Tightly Control Gold Nanoparticle Size

Gold nanoparticles could improve the effectiveness of cancer drugs, many researchers think, by selectively carrying the drugs to tumors. But many synthesis methods yield particles with a broad range of sizes, which probably would not pass muster with regulators. Now researchers have developed a method for making cisplatin-loaded gold spheres with tightly controlled size distribution (Inorg. Chem., DOI: 10.1021/ic202197g).

Side effects often limit patients’ doses of chemotherapy drugs. Researchers have shown in the lab that affixing a drug like cisplatin to nanoparticles allows them to target tumors selectively.

The nanoparticles help the drugs target tumors selectively, because, explains Nial Wheate of the University of Sydney, in Australia, who led the study, “Cancer cells are a bit like dodgy house builders.” They grow so quickly that gaps riddle their vasculature and lymphatic system, he says. Those holes allow nanoparticles of appropriate size to slip in. Inside a cancer cell, Wheate’s group has shown, the acidic intracellular environment releases the particles’ platinum-based drugs (J. Am. Chem. Soc., DOI: 10.1021/ja908117a).

Wheate and his team refined a previously developed procedure for making gold nanoparticles with strict size control; they made particles with diameters of 25, 55, and 90 nm. Using dynamic light scattering and atomic force microscopy, the researchers found that the diameter varied by less than 9% in each batch. To achieve those results, the team made adjustments to the previous synthesis method, including optimizing the concentrations of the reactants and taking special care to exclude water.

The researchers attached cisplatin to the gold particles using polyethylene glycol linkers, so that each of the 25-nm nanoparticles carried around 800 drug molecules and the larger particles carried thousands.

Now Wheate and his team are attaching their nanoparticles to BBR3464, an experimental multiplatinum drug that’s highly effective but also very toxic. It stands to greatly benefit from a nanoparticle delivery system, he says.