Tamara Minko, Ph.D., of Rutgers University, led the team of investigators that developed this novel nanotherapeutic system for treating cancer. She and her colleagues set out to target a signaling pathway that causes tumors to trigger new blood vessel growth and to develop resistance to many anticancer drugs. To shut down this pathway, the investigators developed an antisense oligonucleotide that would bind to and inactivate messenger RNA coding for a protein known as hypoxia-inducible factor-1α, which, when present, activates the targeted pathway.
To deliver this antisense agent to tumor cells, the investigators created a lipid-based nanoparticle, or liposome, that would stably incorporate both the antisense agent and the anticancer drug doxorubicin. The investigators also created two additional liposomes as controls, each of which was loaded with only one of the two therapeutic agents. Tests with both isolated tumor cells and with animals bearing human tumors showed that administration of the multifunctional nanoparticle was more effective at killing tumor cells than was coadministration of the two single-component liposomes. At the same time, the multifunctional liposome produced fewer side effects than did the combination of the two single-component liposomes. The investigators hypothesized that cells may have a limited ability to take up liposomes, so including both drugs in a single liposome would increase cellular uptake of the active ingredients relative to when these agents are delivered using two separate liposomes.