"Trojan Horse" Delivers Drug-Loaded Nanoparticles Deep Into Tumors
One of the most difficult feats to accomplish with today’s anticancer therapies is getting drug into the oxygen- and nutrient-deprived cores of solid tumors. These inaccessible regions may be the source of drug-resistant tumors that can recur years after a patient has completed therapy. One type of cell, however, seems to be able to penetrate the tumor mass, and in fact, these cells, known as macrophages, can account for up to 70 percent of the tumor mass in malignancies such as breast cancer. Unfortunately, these tumor-associated macrophages (TAMs) promote rather than impede tumor progression and foster metastasis.
In a case of turning the tables on these TAMs, a team of investigators led by Susan Clare, M.D., Ph.D., has developed methods for loading gold nanoshells into precursor cells known as monocytes, which turn into macrophages in the tumor environment. The monocytes, in essence, become nanoparticle-loaded Trojan horses. Once inside the tumor core, the gold nanoshells can be activated using near-infrared light, turning them into miniature thermal scalpels that kill tumors from the inside out. The investigators have successfully demonstrated each of these steps in an in vitro tumor spheroid model of breast cancer. The results of these studies appear in the journal Nano Letters.
In the first phase of their investigations, the researchers demonstrated that both monocytes and macrophages internalize large numbers of gold nanoshells without suffering any harmful effects. Next, Clare and her colleagues determined that between 10 and 30 seconds of irradiation with a near-infrared laser produced maximal cell death following nanoshell uptake.
Finally, the researchers tested their Trojan horse on breast cancer tumor spheroids. In this experiment, the spheroids were dosed with a mixture of macrophages and nanoshells for 3 days. In controlled experiments, the researchers added only macrophages to the spheroids. Irradiation of both experimental and control spheroids showed conclusively that those spheroids treated with macrophages and gold nanoshells were annihilated when exposed to near-infrared laser irradiation. The spheroids in the control group showed no ill effects.
This work is detailed in the paper "A cellular Trojan horse for delivery of therapeutic nanoparticles into tumors." Investigators at Rice University and Purdue University also participated in this study. This paper was published online in advance of print publication. An abstract of this paper is available through PubMed.View abstract