Nanoparticles have great potential for patient treatment, but researchers remain unsure of the optimal size and charge of these particles so nanoscale devices can efficiently exit the body once their therapeutic work is done.
If nanoparticles are unable to either biodegrade into safe, biological components or fully leave the body, patients could experience amplified toxicity as they collect in the liver, spleen, and bone marrow. The side effects of in vivo nanoparticle accumulation are unknown. Residual particles could also interfere with medical imaging devices, including CT and ultrasound scans.
Reporting in the October Nature Biotechnology, John Frangioni, an HMS associate professor of radiology and of medicine at Beth Israel Deaconess Medical Center, and his colleagues determined the size requirements and charge characteristics for renal filtration and urinary excretion of inorganic, metal-containing nanoparticles.
Frangioni and his colleagues used quantum dots, metallic semiconducting particles that fluoresce when exposed to blue light, as models for metal-containing nanoparticles due to their similarity in size and composition. The quantum dots can be detected in tissue up to one centimeter thick. By monitoring the quantum dots in mice and rats, the researchers were able to define the optimal size and charge requirements for in vivo particles.
“Semiconductor formulations that exist today all have elements of either known or suspected toxicity,” said Frangioni. “In order for them to be viable, we need to be able to remove them from the body relatively quickly.”
The researchers synthesized several different quantum dots with similar cores and shells, but with varied coatings. Positively or negatively charged quantum dots were trapped in the body because serum proteins bound to them, thereby increasing their overall size to above 15 nm. To prevent proteins from being adsorbed, the researchers chose a zwitterionic coating, cysteine, for the nanoparticles.
“We tried different surface charges and different-sized particles to define what combination would be cleared rapidly from the body after intravenous injection,” said Frangioni, adding that “the blood half-lives are such that there is still adequate time for the dots to find targets.”
Ultimately, the researchers proposed three criteria—dubbed Choi criteria after the lead author, HMS research fellow Hak Soo Choi—that distinguish metal-containing nanoparticles with potential medical application. Nanoparticles should have a hydrodynamic diameter equal to or less than 5.5 nm, contain nontoxic components, and be composed of biodegradable or clearable components. According to Frangioni, “Unless we satisfy these criteria, we don’t consider the nanoparticle as having much medical utility because you run into the problem of extended exposure to the body.”
