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Patricia Van Arnum was executive editor of Pharmaceutical Technology.
Researchers at the Massachusetts Institute of Technology (MIT) recently developed nanoparticles that can be controllably triggered to synthesize proteins.
Researchers at the Massachusetts Institute of Technology (MIT) recently developed nanoparticles that can be controllably triggered to synthesize proteins. The hope is that particles could be used to deliver small proteins that kill cancer cells and eventually larger proteins such as antibodies that trigger the immune system to destroy tumors.
The nanoparticles consist of lipid vesicles filled with the cellular machinery responsible for transcription and translation, including amino acids, ribosomes, and DNA caged with a photo-labile protecting group. These particles served as nanofactories capable of producing proteins including green fluorescent protein (GFP) and enzymatically active luciferase. In vitro and in vivo protein synthesis was spatially and temporally controllable and could be initiated by irradiating micron-scale regions on the timescale of milliseconds. (1).
The researchers designed the new nanoparticles to self-assemble from a mixture that includes lipids, which form the particles’ outer shells, plus a mixture of ribosomes, amino acids, and the enzymes needed for protein synthesis. Also included in the mixture are DNA sequences for the desired proteins. The DNA is trapped by DMNPE, which reversibly binds to it. This compound releases the DNA when exposed to ultraviolet light. In this study, particles were programmed to produce either GFP or luciferase. Tests in mice showed that the particles were successfully prompted to produce protein when UV light shone on them, according to an Apr. 9, 2012, MIT press release.
Although more testing must be done to show that the nanoparticles can reach their intended destination in humans and that they can be used to produce therapeutic proteins, the research is an interesting start. The researchers are working on particles that can synthesize potential cancer drugs by targeting protein production that could be turned on only in the tumor, thereby avoiding side effects in healthy cells. The team also is working on new ways to activate the nanoparticles. Possible approaches include production triggered by acidity level or other biological conditions specific to certain body regions or cells, according to the MIT release.
1. A. Schroeder et al, ” Remotely Activated Protein-Producing Nanoparticles,” Nano Lett., online, DOI: 10.1021/nl2036047, Mar. 20, 2012.