Amphiphilic DNA and its application in biomedicine

In this research, interaction of amphiphilic DNA with liposome membranes was first addressed. Anchoring to liposome membrane showed a liposome composition independent manner. Nearly half of input amphiphilic DNA can be incorporated to the outer membrane leaflet and allows full access to hybridization. Amphiphilic DNA interaction with cell membrane was also investigated and found that it can anchor to the cell membrane regardless of cell types. Next, lipid DNA was inserted in both liposome and cell membranes and by incubation, cellular accumulation of cargo encapsulated in the liposomal core was substantially enhanced when the DNA sequence on the cell was complementary to that on the liposome. Additionally, in mixed cell populations, liposomes discriminate targets by their complementary DNA sequences. Exposure of cells to low temperature and endocytosis inhibitors suggests a caveolae-dependent endocytosis uptake pathway. We also expanded liposomes to other drug carriers. DNA tetrahedron was tailed with free overhangs that can hybridize with cell membrane anchored DNA. After incubation with surface anchored cells, a significantly internalization of these DNA tetrahedron was observed, much higher than those that can not hybridize. Moreover, the DNA mediated internalization of DNA-Au nanoparticles and DNA-functionalized polystyrene particles was studied. In the end, immunostimulatory nanoparticles were synthesized by hybridizing CpG to micelles or liposomes formed from amphiphilic DNA. Administration of these immunostimulatory soft nanoparticles in vivo together with hard core (gold) nanoparticles resulted in distinct spleen dendritic cell activation. Immunostimulatory micelles can effectively promote activation while liposome and gold nanoparticle showed negligible or no effect.

Dissertation: http://hdl.handle.net/11370/d59f613b-78d2-4f38-9b17-bf5c5a68732e