(596ak) Doing Cancer Surgery One Cell At a Time

Cancer chemotherapy is indiscriminate, and is often limited by damage to the heart, liver, kidneys, etc.  The goal of our research is to be able to discriminate cell by cell, that is, to deliver overwhelming doses of a drug to cancer cells while sparing healthy cells from even minor exposure. To do this, we use antibody targeting to selectively deliver gold nanoparticles to cancer cells surrounded by normal cells in culture.  The selectivity of the antibody insures that the targeted cells receive a higher dose of nanoparticles, which are sequestered in endosomal compartments inside the cells.  Fewer nanoparticles at a lower density are found in normal cells.  The cell culture is then irradiated with   with pixosecond-long pulses of near-infrared light.  The light energy is stongly absorbed by the gold nanoparticles and the cells are essentially transparent to the NIR light, making the irradiation completly non-toxic to the cells.  The light energy absorbed by the gold nanoparticles converts instantaneously to heat, raising the nanoparticle temperature sufficiently to melt the gold.  As heat begins to dissipate to the surrounding liquid environment, a small amount of water is vaporized  to generate  transient nanobubbles.  Like the cavitation events in sonication, these nanobubbles are unstable, and rapidly grow, then collapse on themselves, generating substantial liquid and vapor jets.   These tiny jets tear apart individual cancer cells mechanically; with no need for diffusion of heat or a chemical chemotherapy agent. By tuning the incident light energy, only cancer cells that have received multiple nanoparticles initiate the nucleation of nanobubbles and are destroyed, greatly enhancing the selectivity of the antibody. Nanobubbles can be combined with a 10-fold reduced dose of conventional chemotherapy agents such as doxorubicin or cisplatin to enhance the delivery of the drug to the mechanically damaged cells.  The combination of chemotherapy and mechanical damage destroyed even drug-resistant cancer cells without significant damage to normal cells.