What’s the problem, what did we do, and where do we go from here?
Chemotherapy and radiation are currently the most commonly used treatments to battle cancer. However, these therapies indiscriminately attack fast-growing cells, damaging and killing both healthy cells and cancerous cells. Unfortunately, current chemotherapy and radiation treatments are not site specific. Before they arrive to the cancerous site, the chemotherapeutics travel through healthy parts of the body and attack normal cells. Cancer patients are fighting on two fronts: the front against cancer and the front against the actual therapeutics.
Other lesser used cancer treatments include surgery, immunotherapy, hormone therapy, combination therapy, and targeted therapy. Combination therapy is the combination of chemicals or other treatments against the cancerous cells; targeted therapy is when medicine works to target only the cancer in the patient’s body.
To minimize these harmful side effects, we develop a nanostructure that is classified as both combination and targeted therapy. The proposed drug delivery system can carry multiple drugs simultaneously, and then focus the release of those drugs in a small area. Our goals are to:
- Carry multiple drugs in a single system
- Exhibit a triggered response, to focus treatment areas and reduce side effects
- To minimize the exposure times to harmful radiation effects
Our Project Rationale
Triggered release and vesicle adhesion are current research goals surrounding liposomes that could improve the controllability, diversity, and versatility of their applications in drug therapeutics. Classically, these goals have been hindered by difficult formulation steps contributing to instability in the final structure, and especially in triggered release, the sensitivity to the external trigger has been a problem (Yoon et. al. 1). The project seeks to demonstrate the potential of using DNA origami to minimize the direct changes to the liposome composition and to provide a robust platform for the inclusion of functionalities for triggered release.
Our goal has been to develop a proof of concept nanostructure that is based on less specific properties such that it is apparent it can be scaled to other applications. The function of the gold nanoparticles in the system are loosely based on the requirements that the nanoparticle must be positively charged and that it can be excited to produce heat. To develop the project further, another positively charged nanoparticle alternative is Iron Oxide, although there is insufficient information on their compatibility with biological systems.
Additionally, further research could explore several elements. Firstly, the structure of our nanoparticle was spherical, but work such as Wu et. al. 2 show that other configurations such as hollow nanoshells display a higher response to excitation.
Secondly, the current design uses near infrared light to excite the gold nanoparticles, but this wavelength cannot excite the nanoparticles much deeper than skin level. This limits our ability to target cancerous regions deeper in the body. For future experiments, shorter wavelength radiation could be experimented with to find a balance between exciting the nanostructure without causing adverse effects to the patient.
Thirdly, improvements can also be made upon the structure itself. In order to maximize drug delivery, a greater number of liposomes could be linked to the main DNA structure. This can be done by either improving the liposome-DNA binding process, or by using different origami shapes to potentially bind more liposomes to each structure.
Lastly, improvement can be made by adding specific binding sites to the liposomes and DNA origami. Specific binding sites can regulate the amount and the type of liposomes binding to the DNA origami. Binding sites could be designed by modifying the oligonucleotides in the DNA origami and the head group of the phospholipids of the liposomes.
Yoon, G., Park, J.W., Yoon, I-S. (2013). Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs): recent advances in drug delivery. Pharmaceutical Investigation, 43(5): 353-62 ↩
Wu, G., Milkhailovsky, A., Khant, H., Fu, C., Chiu, W., & Zasadzinski, J. (2008). Remotely triggered liposome release by near-infrared light absorption via hollow gold nanoshells. Journal of the American Chemical Society, 130(26), 8175-8175. doi:10.1021/ja802656d ↩