Hypoxia is a state of oxygen deprivation characteristic of many solid cancerous tumors. Oxygen starvation helps tumors resist both radiotherapy and chemotherapy. Treatment with small interfering RNA (siRNA) is toxic to such tumors through a process known as gene silencing, but getting these nucleic acids deep into the tumor is challenging.
Hypoxic cancer cells consume more glucose than healthy cells, an effect that Wei Zhang, Nantong University, China, and colleagues hope to use in order to guide siRNA to its target. They covered quantum dots with a polyarginine peptide (for nucleic acid binding), covalently linked to a glucose-like molecule (for tumor targeting). The linker was a pH-sensitive hydrazone, designed to break after cell uptake, so that the nanoparticle delivers its bound siRNA instead of being recycled by the cell’s endosomes.
The team tested this nanoparticle construct for its ability to bind siRNA and deliver it into cancer cells in a range of in vitro and in vivo experiments. They observed gene silencing, anticancer activity, and less organ toxicity than quantum dots alone in mice. Furthermore, as quantum dots are fluorescent, the nanoparticles could be tracked in real time around the body of the mouse, revealing excellent in vivo tumor targeting.
- pH-responsive hybrid quantum dots for targeting hypoxic tumor siRNA delivery,
HongYan Zhu, ShengYu Zhang, Yong Lin, GuoLiang Meng, Yu Yang, Wei Zhang,
J. Control. Release 2015.