Scientists had originally thought they could create a “magic bullet” to patrol for cancer cells in the body. However, this has not been feasible; only 5% of injected nanoparticles reach the targeted tumor using current delivery techniques. Simply put, scientists need to figure out how to inject a treatment into the body and then selectively direct that treatment to cancer cells if the treatments are to work to their full potential.
With this in mind, Mao and his research team aim to optimize nanoparticle design to improve delivery to tumor cells by making the nanoparticles more stable in the body’s circulatory system. Mao’s group uses custom polymers and DNA scaffolds to create nanoparticles. The DNA serves dual purposes, as a building block for the particles and as a signal for cancer cells to express certain genes (for example, cell suicide genes). By tuning the polarity of the solvent used to fabricate the nanoparticles, the group can control nanoparticle shape, forming spheres, ellipsoids, or long “worms” while leaving everything else about the nanoparticles constant. This allows them to test the effects of nanoparticle size on gene delivery. Interestingly, “worms” appear more stable in the blood stream of mice and are therefore better able to deliver targeted DNA. Studies of this type will allow intelligent nanoparticle design by illuminating the key aspects for efficient tumor targeting.
Currently, Mao’s group is extending their fabrication methods to deliver other payloads to cancer cells. Small interfering ribonucleic acid (siRNA), which can suppress expression of certain genes, can also be incorporated into nanoparticles. Finally, Mao noted that the “worm”-shaped nanoparticles created by the group look like naturally occurring virus particles, including the Ebola and Marburg viruses. In the future, the group hopes to use their novel polymers and fabrication techniques to see if shape controls virus targeting to specific tissues in the body. This work could have important applications in virus treatment.