One challenge in treating cancer is how to kill cancer cells without damaging cells in a surrounding area. In the July 28 issue of ACS NANO, a team at the University of California, Santa Barbara, reported a method that can do just that.The method uses laser-induced release of a drug from a nanoparticle – after targeting the nanoparticle to the inside of the cancer cell – to switch off a gene that the cell may require to survive. The researchers showed that only those cells with the nanoparticles in them, and in the path of the light, were affected by the drug.Researchers have reported a novel means of delivering drugs into cancer cells by targeting them to the insides of the cells and then activating them with near-infrared light. Shown here is the near-infrared laser pathway into the cell-culture plate used in the study. The pathway was traced by visible light for the photo.Gary B. Braun, lead author of the study, said his group was motivated by a lack of methods for controlling drug release from nanoparticles using near-infrared or infrared light, the wavelengths most able to penetrate to the deeper regions of tissue.There are ways to “uncage” molecules using chemical group cleavage by UV or near-UV light, but these have issues of wavelength and limited chemical flexibility, complex synthesis and “leakiness” of the protecting group.Other groups have demonstrated use of pulsed lasers to ablate thiols from solid gold nanoparticles. The Santa Barbara researchers understood that, to achieve drug release, they had only to tune the plasmon absorption with the laser wavelength. So they used nanoshells to absorb where needed – in this case, at 800 nm for their femtosecond laser.“Nanoshells had been used for general heating of their surroundings and tissue destruction,” Braun said, “but we were able to show the pulsed format to be gentle and accurate for dosed release without killing, per se.”The nanoshell can carry many copies of a thiol drug or polymer while keeping them sterically protected in the layer until release. “This naturally allows a core/drug/shell strategy,” Braun said, “where the shell can do the targeting of the tissue or cancer cells, while the cargo is kept at the surface until laser activation.” Upon activation, the thiol-gold bond breaks, and the molecules diffuse outward.The novel drug delivery system could advance a range of applications. Understanding the fundamentals of cell networks, tissue development, stem cells and cancer heterogeneity likely will require temporal and spatial control of drug concentration, Braun said. In vivo cancer therapeutics also could benefit from the additional control, which could help limit the side effects of drugs.The researchers are continuing to develop the system. They currently are working to combine peptide targeting agents on the surface with various drug cargo – RNA and small-molecule chemotherapy agents, for example – for testing against in vivo models of tumors in mice.